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Preparation method of temperature response type nanoliposomes coated with matrix metalloproteinase inhibitors

A protease inhibitor and nano-liposome technology, applied in the field of nano-liposome and its preparation, can solve the problems of easy leakage of drugs and low stability, so as to improve anti-tumor ability, improve stability, and improve targeting sexual effect

Inactive Publication Date: 2017-12-15
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, at present, drug liposomes generally have the disadvantages of low stability and easy leakage of drugs in the circulation.

Method used

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  • Preparation method of temperature response type nanoliposomes coated with matrix metalloproteinase inhibitors
  • Preparation method of temperature response type nanoliposomes coated with matrix metalloproteinase inhibitors
  • Preparation method of temperature response type nanoliposomes coated with matrix metalloproteinase inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] prescription:

[0034]

[0035] Preparation:

[0036] Add 3 mg of Marimastat to 3 mL of pH 6.5 phosphate buffer, sonicate until dissolved, and set aside. 51.6 mg of dipalmitoyl phosphatidyl choline, 6 mg of stearoyl lysolecithin, and 2.4 mg of polyethylene glycol material were added to 8 mL of a mixed solution of chloroform and methanol (volume ratio of 3:1), and sonicated for half a minute. After complete dissolution, put it on a rotary evaporator at 45°C and remove the organic solvent under reduced pressure, and then use the prepared 3mL Marimastat solution to hydrate for 1h at 45°C. The solution obtained after hydration was placed in a probe sonicator, and the power was 190W for 10 minutes. The ultrasonic mode was turned on for 3s and stopped for 4s. The solution obtained after sonication was extruded through a 0.22 μm filter to obtain the target solution.

[0037] The particle size, polydispersity coefficient, and Zeta potential of the temperature-responsive n...

Embodiment 2

[0039] prescription:

[0040] Carboxyfluorescein 6mg

[0041] Dipalmitoylphosphatidylcholine 107.50mg

[0042] Stearoyl lysolecithin 12.50mg

[0043] Preparation:

[0044] 6 mg of carboxyfluorescein was added to 6 mL of pH 6.5 phosphate buffer, sonicated in the dark until dissolved, and set aside. 107.50 mg of dipalmitoyl phosphatidyl choline and 12.50 mg of stearoyl lysolecithin were added to 12 mL of a mixed solution of chloroform and methanol (3:1 by volume), and sonicated for half a minute. After the complete dissolution, put it on a rotary evaporator at 50°C and remove the organic solvent under reduced pressure. After drying, use the prepared 6mL carboxyfluorescein solution to hydrate for 1h at 50°C in the dark. The solution obtained after hydration was placed in a probe sonicator, and the power was 190W for 10 minutes. The ultrasonic mode was turned on for 3s and stopped for 4s. The solution obtained after sonication was extruded through a 0.22 μm filter to obtain the...

Embodiment 3

[0046] prescription:

[0047] Carboxyfluorescein 4mg

[0048] Dipalmitoylphosphatidylcholine 71.01mg

[0049] Stearoyl lysolecithin 8.99mg

[0050] Preparation:

[0051] 4 mg of carboxyfluorescein was added to 4 mL of phosphate buffer at pH 6.5, sonicated in the dark until dissolved, and set aside. 71.01 mg of dipalmitoyl phosphatidyl choline and 8.99 mg of stearoyl lysolecithin were added to 8 mL of a mixed solution of chloroform and methanol (3:1 by volume), and sonicated for half a minute. After the complete dissolution, put it on a rotary evaporator at 50°C and remove the organic solvent under reduced pressure. After drying, use the prepared 6mL carboxyfluorescein solution to hydrate for 1h at 50°C in the dark. The solution obtained after hydration was placed in a probe sonicator, and the power was 190W for 10 minutes. The ultrasonic mode was turned on for 3s and stopped for 4s. The solution obtained after sonication was extruded through a 0.22 μm filter to obtain the...

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Abstract

The invention provides a temperature-responsive nano-liposome carrying a matrix metalloproteinase inhibitor and a preparation method thereof, belonging to the field of pharmaceutical preparations. It is made of the following ingredients: active drug, main phospholipid, lysophospholipid, polyethylene glycol material. Based on the properties of the temperature-responsive nanoliposomes loaded with matrix metalloproteinase inhibitors as nano-preparations, matrix metalloproteinase inhibitors can be effectively and quickly delivered to tumor sites, which improves the targeting of drugs and reduces the It reaches the amount of drug in normal tissue; based on the temperature sensitivity of the temperature-responsive nanoliposome, it can significantly improve the stability of the preparation at normal physiological temperature and reduce the leakage of the drug in the blood circulation; After the site is heated, the drug can be quickly released to the tumor site, which significantly improves the anti-tumor ability of the drug. The present invention is characterized in that the stability is better than that of the conventional liposome, and the liposome has tumor targeting property and can improve the curative effect of the medicine.

Description

technical field [0001] The present invention relates to a nano-liposome and a preparation method thereof. Specifically, it relates to a temperature-responsive nanoliposome encapsulating a matrix metalloproteinase inhibitor and a preparation method thereof. Background technique [0002] Invasion and metastasis are important biological characteristics of malignant tumors and the main cause of death in cancer patients. Tumor invasion and metastasis is a complex process. Tumor cells must degrade the extracellular matrix in order to invade surrounding tissues and invade blood vessels, thereby metastasizing to distant tissues. In the tumor microenvironment, matrix metalloproteinases are a class of zinc-dependent endogenous proteolytic enzymes, which are the main enzymes that degrade the extracellular matrix. In the extracellular matrix, matrix metalloproteinases maintain a balance with tissue inhibitor of metalloproteinases, endogenous matrix metalloproteinase inhibitors, but i...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/16A61K47/24A61P35/00A61P35/04
CPCA61K9/1271A61K9/1277A61K31/16A61K47/24
Inventor 尹莉芳何伟吕雅琪
Owner CHINA PHARM UNIV
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