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Mitochondria-targeted polysaccharide nano preparation and preparing method thereof

A nano-preparation, mitochondrial technology, applied in non-active ingredients medical preparations, medical preparations containing active ingredients, glycopeptide ingredients, etc., can solve problems such as drug leakage, achieve increased toxicity, reasonable preparation method design, and difficult The effect of leakage

Active Publication Date: 2016-06-15
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in this technical solution, since TPP-DOX has a certain amphiphilicity (that is, both hydrophilic and lipophilic) in the way the drug is carried, the method of physically encapsulating TPP-DOX in the carrier may cause Cause drug leakage during storage

Method used

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  • Mitochondria-targeted polysaccharide nano preparation and preparing method thereof
  • Mitochondria-targeted polysaccharide nano preparation and preparing method thereof
  • Mitochondria-targeted polysaccharide nano preparation and preparing method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0041] Dissolve 40mg of triphenylphosphine TPP in 15ml of ultrapure water, 19mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide EDC, and 12mg of N-hydroxysuccinimide NHS in 1ml of ultrapure water Add the pure water to the TPP solution drop by drop, adjust the pH to 5.5, and stir the solution on a magnetic stirrer for 40 minutes. Dissolve 22 mg n-BOC-1,6-diaminohexane hydrochloride in 5 ml of water, add dropwise to the activated TPP solution, adjust the pH to 7.5, react and stir for 4 hours, and freeze-dried TPP-C 6 -BOC was dissolved in 20ml of methanol, 2ml of trifluoroacetic acid was added, the reaction was stirred for 1 hour, transferred to an eggplant-shaped bottle, evaporated to dryness by rotary evaporation, a yellow oily substance appeared, and saturated NaHCO was added 3 solution, extracted with chloroform, combined the chloroform layers, and evaporated to dryness to obtain TPP-C 6 -NH 2 .

[0042] Dissolve 40mg of hyaluronic acid HA (molecular weight 150000Da) in ...

Embodiment 2

[0045] Dissolve 40mg of triphenylphosphine TPP in 15ml of ultrapure water, 19mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide EDC, and 12mg of N-hydroxysuccinimide NHS in 1ml of ultrapure water Add the pure water to the TPP solution drop by drop, adjust the pH to 5.5, and stir the solution on a magnetic stirrer for 40 minutes. Dissolve 22 mg n-BOC-1,6-diaminohexane hydrochloride in 5 ml of water, add dropwise to the activated TPP solution, adjust the pH to 7.5, react and stir for 4 hours, and freeze-dried TPP-C 6 -BOC was dissolved in 20ml of methanol, 2ml of trifluoroacetic acid was added, the reaction was stirred for 1 hour, transferred to an eggplant-shaped bottle, evaporated to dryness by rotary evaporation, a yellow oily substance appeared, and saturated NaHCO was added 3 solution, extracted with chloroform, combined the chloroform layers, and evaporated to dryness to obtain TPP-C 6 -NH 2 .

[0046] Dissolve 40mg of hyaluronic acid HA (molecular weight 150000Da) in ...

Embodiment 3

[0049] Dissolve 40mg of triphenylphosphine TPP in 15ml of ultrapure water, 19mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide EDC, and 12mg of N-hydroxysuccinimide NHS in 1ml of ultrapure water Add the pure water to the TPP solution drop by drop, adjust the pH to 5.5, and stir the solution on a magnetic stirrer for 40 minutes. Dissolve 22 mg of n-BOC-1,6-diaminohexane hydrochloride in 5 ml of water, add dropwise to the activated TPP solution, adjust the pH to 7.5, stir the reaction for 4 hours, and freeze-dry. TPP-C after lyophilization 6 -BOC was dissolved in 20ml of methanol, 2ml of trifluoroacetic acid was added, the reaction was stirred for 1 hour, transferred to an eggplant-shaped bottle, evaporated to dryness by rotary evaporation, a yellow oily substance appeared, and saturated NaHCO was added 3 solution, extracted with chloroform, combined the chloroform layers, and evaporated to dryness to obtain TPP-C 6 -NH 2 .

[0050] Dissolve 40mg of hyaluronic acid HA (mol...

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Abstract

The invention relates to a mitochondria-targeted polysaccharide nano preparation. The mitochondria-targeted polysaccharide nano preparation comprises water-soluble polysaccharide, triphenylphosphine and antitumor medicine containing primary amine or hydroxyl groups, wherein the triphenylphosphine modifies the antitumor medicine through an amido bond or an ester bond and is connected to the water-soluble polysaccharide through an ionic bond manner; or the triphenylphosphine modifies the water-soluble polysaccharide through an amido bond, and the antitumor medicine is combined to the water-soluble polysaccharide in an amido bond or hydrazone bond manner. The invention further relates to a preparing method of the mitochondria-targeted polysaccharide nano preparation. The polysaccharide nano preparation has the advantage of acid-sensitive drug releasing in a tumor microenvironment and is simple in process. Compared with the single solution of traditional antitumor medicine, the preparation has the advantages that the preparation' toxicity to tumor cells is increased greatly, and the preparation is widely applicable to the field of antitumor tolerance researches.

Description

technical field [0001] The invention relates to a polysaccharide nano-preparation and its preparation, in particular to a mitochondria-targeted polysaccharide nano-preparation and a preparation method thereof. Background technique [0002] In the clinical treatment of tumors, surgery, radiotherapy, and chemotherapy are the three traditional treatment options, among which chemotherapy occupies an irreplaceable important position. However, the multidrug resistance (MDR) of tumor cells to chemotherapy drugs is an important reason for the failure of its clinical treatment. MDR is an important cellular defense mechanism for tumor cells to avoid drug attacks. It is a phenomenon in which tumor cells are resistant to one chemotherapeutic drug and are also cross-resistant to other anti-tumor drugs with different structures and different mechanisms of action. , and its mechanism is very complex. [0003] Mitochondria are the regulatory centers of apoptosis. The stimulation of apopt...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/704A61K38/14A61K31/4745A61K31/337A61P35/00
CPCA61K31/337A61K31/4745A61K31/704A61K38/14
Inventor 韩旻刘惠娜高建青郭望葳皇甫铭一郭宁宁
Owner ZHEJIANG UNIV
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