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Paclitaxel liposome encapsulated by hyaluronic acid oligosaccharide and preparation method thereof

A technology of hyaluronic acid and oligosaccharides, which is applied in liposome delivery, drug combination, antineoplastic drugs, etc., can solve problems that have not been reported yet, and achieve the effect of improving bioavailability, stable properties, and uniform size

Active Publication Date: 2014-10-15
SHANGHAI SIXTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008]However, there are no reports about the preparation of PTX nanomaterials from hyaluronan oligosaccharides (oHA) at home and abroad

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Weigh 820mg DLPE, 380mg DLPG and 40mg PTX, add 20ml organic solvent and dissolve in a 250ml round bottom flask, mix well at 50°C for 10-20min, vacuum-dry for 4h, freeze-dry at -80°C for 2h Water hydration, 45°C, 150r / min, at least 2h; at the same time, dissolve 10mg hyaluronic acid oligosaccharides (oHA) and 200mg ethyldimethylaminepropylcarbodiimide (EDAC) in 5ml acetate buffer solution, 37°C, 150 r / min, pre-incubated for 2 hours; add the suspension after hydration to the buffer after pre-incubation, and incubate overnight at 37°C, 150 r / min; then double-distilled water dialysis for 24 hours; Homogenize under high pressure, with a pressure of about 15,000, and cycle 10 times; filter with a 0.22 μm filter in an ultra-clean bench; sub-package, freeze overnight at -80°C, and drain into powder to prepare paclitaxel liposomes wrapped in hyaluronic acid oligosaccharides ( oHA-PTX-Lipid).

[0046] The average particle size of the oHA-PTX-Lipid prepared in this example is abo...

Embodiment 2

[0048] Weigh 1440.3mgDLPE, 175.0mgDLPG and 50.0mgPTX, add 15ml of organic solvent to dissolve in a 250ml round bottom flask, mix well at 50°C for 10-20min, vacuum dry for 2h, freeze-dry at -80°C for 2h Water hydration, 45°C, 150 r / min, at least 2h; at the same time, 14mg oHA and 240mg EDAC were dissolved in 7ml acetate buffer, 37°C, 150r / min, pre-incubated for 2h; Add the turbid solution to the buffer after pre-incubation, incubate overnight at 37°C, 150 r / min; dialyze in double distilled water for 24 hours; frozen overnight at -80°C, and dried into a powder to obtain paclitaxel liposomes (oHA-PTX-Lipid) encapsulated by hyaluronic acid oligosaccharides.

[0049] The average particle size of the oHA-PTX-Lipid prepared in this example is about 120nm, with uniform size and stable properties. The content of PTX measured by HPLC method is 5wt%, and the content of oHA measured by carbazole method is 1wt%. It acts on breast tumor cell MDA-MB-231, and detects its killing effect on b...

Embodiment 3

[0051] Weigh 600.0mg DLPE, 600.0mg DLPG and 40.0mg PTX, add 15ml of organic solvent to dissolve in a 250ml round bottom flask, mix well at 50°C for 10-20min, vacuum dry for 2h, freeze-dry at -80°C for 2h overnight, and use Hydrate with 35ml double distilled water, 45°C, 150 r / min, at least 2h; at the same time, dissolve 14mg oHA and 240mg EDAC in 7ml acetate buffer, 37°C, 150r / min, pre-incubate for 2h; After the completion, the suspension was added to the pre-incubation buffer, incubated overnight at 37°C, 150 r / min; double distilled water dialysis for 24 hours, high pressure homogenization, pressure about 15,000, cycle 10 times, ultra-clean bench 0.22μm filter Filtrate, subpackage, freeze at -80°C overnight, and drain into powder to prepare paclitaxel liposomes encapsulated by hyaluronic acid oligosaccharides.

[0052] The average particle size of the oHA-PTX-Lipid prepared in this example is about 120nm, with uniform size and stable properties. The content of PTX calculated...

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Abstract

The invention relates to a preparation method of paclitaxel liposomes wrapped in hyaluronic acid oligosaccharides, comprising the following steps: weighing phospholipids and paclitaxel to prepare a phospholipid-paclitaxel honeycomb film; hydrating the prepared film; Pre-incubation of sugar and ethyldimethylaminopropylcarbodiimide in acetate buffer; add the hydrated suspension to oligosaccharide-acetate buffer and incubate; the obtained The mixture was separated to prepare paclitaxel liposomes coated with oligosaccharides. The paclitaxel liposome encapsulated by the oligosaccharide has uniform size, high encapsulation efficiency and stable property, and effectively improves the solubility of paclitaxel in water. In addition, for tumor cells with high expression of CD44 (such as breast cancer, etc.), the complex has strong targeting (hyaluronic acid specifically binds to CD44), can effectively increase the concentration of paclitaxel in the tumor site, and reduce the dosage of paclitaxel , while reducing the toxic effect of the drug on the human body and enhancing its bioavailability.

Description

technical field [0001] The invention relates to a liposome, in particular to a hyaluronic acid oligosaccharide-wrapped paclitaxel liposome and a preparation method thereof. Background technique [0002] Tumor treatment is an unsolved problem today and a major challenge that the medical community has been facing. Drug therapy is an important means of tumor treatment. Although traditional anti-tumor drugs have achieved certain curative effects, their allergic reactions, inhibition of bone marrow hematopoietic system, hair loss and other toxic and side effects greatly limit their clinical application and become the mainstay of clinical treatment. One of the puzzles. How to improve the curative effect of tumor treatment is an urgent problem to be solved in modern medicine. In response to this shortcoming, targeted therapy has become a research hotspot in tumor therapy, and the use of nanometer as a targeting carrier has become the focus of research by medical scholars. [000...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K31/337A61K47/36A61P35/00
Inventor 高锋刘鷖雯何怡青杨翠霞刘华
Owner SHANGHAI SIXTH PEOPLES HOSPITAL
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