Paclitaxel micelle drug load system and preparation method thereof

A drug-carrying system, paclitaxel technology, applied in the direction of pharmaceutical formulations, anti-tumor drugs, drug combinations, etc., can solve the problems of slow dilution of injections, inconsistent drug levels, limited capacity, etc., to achieve good industrial application prospects and convenient storage and transport, increase the effect of force

Inactive Publication Date: 2015-08-26
CHANGZHOU TARGET MEDICINE TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because it is almost insoluble in water and has poor oral absorption, it can only be administered by injection at present. The listed preparation (trade name Taxol) is obtained by adding polyoxyethylene castor oil ( EL) to increase drug solubility
Experiments have shown that there are many shortcomings in Taxol: (1) due to the use of EL is easy to cause allergic reactions, so patients need anti-allergic treatment before medication; (2) Poor drug stability and low injection availability: the above-mentioned preparations are easy to precipitate after dilution, and need to pass through a special filter device during administration. Moreover, the injection dilution process needs to be carried out slowly, and the degree of drug precipitation is often inconsistent due to different operators, resulting in inaccurate drug doses entering the body, resultin

Method used

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  • Paclitaxel micelle drug load system and preparation method thereof
  • Paclitaxel micelle drug load system and preparation method thereof
  • Paclitaxel micelle drug load system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The synthesis of embodiment 1mPEG-PLA-Phe (Boc)

[0037] 5g of methoxypolyethylene glycol with a molecular weight of 2000, 6g of lactide, 6mg of stannous octoate, and 10ml of toluene were added to the polymerization bottle, and the toluene was removed by vacuum at 50°C to remove the moisture in the system, and the vacuum-sealed polymerization bottle was placed at 100 o Polymerize at ℃ for 24 hours, dissolve the product with dichloromethane, and precipitate with ether to obtain methoxypolyethylene glycol-polylactide block copolymer (MPEG-PLA).

[0038] Dissolve 6.65g of Boc phenylalanine in 50ml of anhydrous ethyl acetate, add 3.5ml of triethylamine, add 3.05ml of pivaloyl chloride after the solution is cooled to -10°C, heat up the reactant to 0°C for 2 hours, then continue the reaction at room temperature 2h. The insoluble matter was removed by filtration, and the ethyl acetate was removed by rotary evaporation to obtain a white solid which was Boc phenylalanine-pivali...

Embodiment 2

[0041] Preparation of embodiment 2MPEG-PLA-Phe(Boc) / paclitaxel micelles

[0042] Dissolve 20mg paclitaxel, 100mg MPEG-PLA-Phe (Boc) in 5ml ethanol, remove the solvent by rotary evaporation at 55°C, add 5ml ultrapure water to dissolve the drug film, and the obtained micellar solution is filtered through a 0.22μm sterile membrane and freeze-dried to obtain paclitaxel gel Bunch of freeze-dried powder. Its resolubility is good, and the change of particle size distribution before and after reconstitution is small, and the detailed results are shown in the attached figure 2 And attached image 3 .

[0043] Test example 3 pharmacokinetic test

[0044] A. Experimental animals:

[0045] Male SD rats, weighing 240±20g, were randomly divided into four groups, with 6 rats in each group, and they were reserved.

[0046] B. Experimental preparation:

[0047] Preparation I: It is paclitaxel micelle freeze-dried powder preparation for testing, prepared according to Example 2, batch num...

Embodiment 4

[0057] Embodiment 4 pharmacodynamics test

[0058] 4.1 Inhibitory effect of paclitaxel micelles for injection on xenograft tumors of prostate cancer PC-3A doxorubicin-resistant cells in nude mice

[0059] Male BALB / c nude mice were subcutaneously inoculated with 5×10 6 PC-3A cells. After about a week, the average volume of tumors in tumor-bearing mice reached 100mm 3 For the above, 30 tumor-bearing mice were randomly stratified and grouped according to tumor volume, respectively: vehicle group, preparation I (20 mg / kg, derived from Example 2), preparation II, preparation III, and preparation IV refer to patent CN201110231519.7 Prepared with CN01809632.8 (20mg / kg), administered intravenously, once every 3 days, for a total of 3 times. During the experiment, the animal tumor volume was determined every week (calculation formula ab 2 / 2, a and b are the length and width of the tumor, respectively) and body weight. The result is as Figure 5 As shown, in the late stage of th...

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PUM

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Abstract

The invention relates to a novel micelle drug load system formed by an amphiphilic segmented copolymer and paclitaxel. The amphiphilic segmented copolymer comprises a hydrophilic chain segment and a hydrophobic chain segment, the hydrophilic chain segment is polyethylene glycol monomethyl ether, the hydrophobic chain segment is polycaprolactone, and the end group of the hydrophobic chain segment is terminated by a hydrophobic group. The hydrophobic group is tertbutyloxycarbonyl phenylalanine, so the compatibility of a drug molecule with the hydrophobic chain segment in the segmented copolymer is improved, the interaction between the drug molecule and the segmented copolymer is increased, a large space is provided for accommodating the drug molecule, and a prepared micelle can effectively restrict the drug molecule in the core of the micelle, thereby a drug loaded micelle with high stability is obtained.

Description

technical field [0001] The invention relates to a drug-carrying system formed by an amphiphilic block copolymer and paclitaxel and a preparation method thereof, belonging to the field of nano-medicine preparations. Background technique [0002] Tumor is a kind of disease that seriously threatens the safety of human life. The study of safe and effective anti-tumor drugs is of great significance to improve the quality of human life. [0003] Paclitaxel (PTX) is a very effective and broad-spectrum anti-tumor drug. Its mechanism of action is mainly to polymerize and stabilize microtubules, which can cause fast-dividing tumor cells to fix in the mitotic stage and block the replication of cancer cells. die. [0004] [0005] In vitro experiments have shown that paclitaxel has a significant radiosensitizing effect and can stop tumor cells in the G2 and M phases that are sensitive to radiotherapy. However, because it is almost insoluble in water and has poor oral absorption, it...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K9/19A61K31/337A61K47/34A61K45/00C08G63/91C08G63/664A61P35/00
Inventor 刘珂郎跃武许卉范华英其他发明人请求不公开姓名
Owner CHANGZHOU TARGET MEDICINE TECH CO LTD
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