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Composite temperature-sensitive vesicles for gemcitabine hydrochloride high-efficiency thermotherapy and preparation method

A technology of gemcitabine hydrochloride and thermal chemotherapy, which is applied in the fields of polymer materials and biomedical engineering, and can solve problems such as unrelated research

Active Publication Date: 2021-06-04
JIANGSU QINGJIANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to effectively enhance the clinical efficacy of gemcitabine hydrochloride, the involved nano-drug carriers need to be designed according to the heat-sensitizing properties of the drug, but there is no relevant research at present

Method used

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  • Composite temperature-sensitive vesicles for gemcitabine hydrochloride high-efficiency thermotherapy and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Weigh 20 mg of PLA- b -p(NIPAM- co -DMAM), wherein the molecular weight of PLA: p(NIPAM- co The molecular weight of -DMAM) is 3: 1, takes by weighing 40mg in addition, and particle diameter is the superparamagnetic nanoparticle MnFe of 8nm 2 o 4 , both were dissolved in 5ml of dichloromethane to obtain an organic phase.

[0027] Weigh 0.5 mg of gemcitabine hydrochloride and disperse in 1 ml of deionized water to obtain an aqueous phase.

[0028] Dissolve PVA with a molecular weight of 31000 in deionized water to prepare an aqueous solution with a concentration of 0.1 mg / mL.

[0029]Under the conditions of ice-water bath and ultrasonic, the water phase was dropped into the organic phase, and the primary emulsion was obtained after thorough mixing. Add 20mL of PVA aqueous solution to the primary emulsion in an ice-water bath and ultrasonic conditions to obtain a secondary emulsion. The secondary emulsion was dropped into 80 mL of deionized water under the conditio...

Embodiment 2

[0033] Weigh 40 mg of PCL- b -p(NIPAM- co -DMAM), wherein the molecular weight of PCL: p(NIPAM- co The molecular weight of -DMAM) is 5: 1, takes by weighing 60mg in addition, and particle diameter is the superparamagnetic nanoparticle Mn of 12nm 0.6 Zn 0.4 Fe 2 o 4 , both were dissolved in 8ml of dichloromethane to obtain an organic phase.

[0034] Weigh 2 mg of gemcitabine hydrochloride and disperse in 2 ml of deionized water to obtain an aqueous phase.

[0035] Dissolve PVA with a molecular weight of 47000 in deionized water to prepare an aqueous solution with a concentration of 0.05 mg / mL.

[0036] Under the conditions of ice-water bath and ultrasonic, the water phase was dropped into the organic phase, and the primary emulsion was obtained after thorough mixing. The primary emulsion was added with 60 mL of PVA aqueous solution under the conditions of ice-water bath and ultrasonic to obtain the secondary emulsion. The secondary emulsion was dropped into 200 mL of ...

Embodiment 3

[0040] Weigh 20 mg of PLGA- b -p(NIPAM- co -DMAM), wherein the molecular weight of PLGA: p(NIPAM- co The molecular weight of -DMAM) is 8: 1, takes by weighing 40mg in addition, and particle diameter is the superparamagnetic nanoparticle Mn of 16nm 0.4 Zn 0.6 Fe 2 o 4 , both were dissolved in 4ml of dichloromethane to obtain an organic phase.

[0041] Weigh 0.5 mg of gemcitabine hydrochloride and disperse in 0.8 ml of deionized water to obtain an aqueous phase.

[0042] Dissolve PVA with a molecular weight of 47,000 in deionized water to prepare an aqueous solution with a concentration of 0.1 mg / mL.

[0043] Under the conditions of ice-water bath and ultrasonic, the water phase was dropped into the organic phase, and the primary emulsion was obtained after thorough mixing. Add 40 mL of PVA aqueous solution to the primary emulsion in an ice-water bath under ultrasonic conditions to obtain a secondary emulsion. The secondary emulsion was dropped into 180 mL of deionized...

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Abstract

The invention discloses a compound temperature-sensitive vesicle carrier capable of significantly improving the curative effect of gemcitabine hydrochloride thermochemotherapy and a preparation method thereof, belonging to the fields of polymer materials and medical engineering. The composite thermosensitive vesicles are formed by encapsulating hydrophobic superparamagnetic nanoparticles and hydrophilic gemcitabine hydrochloride by an amphiphilic thermosensitive polymer through a double emulsion method, in which the drug gemcitabine hydrochloride is encapsulated in the hydrophilic inner core of the composite thermosensitive vesicles In , hydrophobic superparamagnetic nanoparticles are encapsulated in a bilayer hydrophobic membrane of composite thermosensitive vesicles. Since the composite temperature-sensitive vesicles can more precisely control the magnetic hyperthermia and temperature-controlled drug release behavior mediated by it, the interval between gemcitabine hydrochloride chemotherapy and thermotherapy can be realized, thereby maximizing the curative effect of gemcitabine hydrochloride thermotherapy.

Description

technical field [0001] The invention belongs to the field of macromolecular materials and biomedical engineering, and specifically relates to a nano-carrier that can effectively improve the cytotoxicity of chemotherapy drug gemcitabine hydrochloride, thereby realizing high-efficiency thermal chemotherapy of gemcitabine hydrochloride. Background technique [0002] Gemcitabine hydrochloride is a typical cell cycle inhibitory drug, which usually acts on cells in the S phase, that is, cells in the rapid proliferation phase. Therefore, gemcitabine hydrochloride is mostly used in the treatment of highly malignant advanced or metastatic solid tumors, including non-small cell lung cancer, pancreatic cancer, bladder cancer, breast cancer and ovarian cancer, etc., and has broad market prospects. However, the metabolism of gemcitabine hydrochloride is very fast in the body, and the half-life is only 17 minutes. Therefore, in clinical application, a higher dosage must be ensured to main...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K9/127A61K47/34A61P35/00A61K31/7068
CPCA61K9/1273A61K31/7068A61K41/0052A61K47/34A61P35/00A61K2300/00
Inventor 屈阳辛渊蓉赖文龙王维许颖刘宏飞
Owner JIANGSU QINGJIANG PHARMA