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Nanovesicle drug formed by self-assembly and its preparation method and application

A technology of nanovesicles and drugs, applied in the direction of nano drugs, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc.

Active Publication Date: 2022-03-25
YANTAI LANNACHENG BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the combined nano-preparation exists in the form of fibers or micelles, and the length of the micelles is usually hundreds of nanometers or even micron. Nanoparticles of this form cannot be used for drug delivery in vivo by injection. There are limitations in animal experiments and clinical promotion

Method used

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  • Nanovesicle drug formed by self-assembly and its preparation method and application
  • Nanovesicle drug formed by self-assembly and its preparation method and application
  • Nanovesicle drug formed by self-assembly and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Example 1: Self-assembly of EB-CPT alone.

[0079] The self-assembly process of EB-CPT is quite simple. We tested two strategies for the self-assembly of EB-CPT into micelles. The first method was previously described as spontaneous self-assembly by directly suspending EB-CPT powder in deionized water (ACS Nano, 2017, 11, 8838-8848). To complete and compare the co-assembly process of EB-CPT and PTX, we also tested the self-assembly process of EB-CPT by solvent evaporation. In a typical procedure, 100 μL of 5 mg / mL EB-CPT was dissolved in methanol and added dropwise to a solution of 2 mL deionized water. The solution was left open to evaporate methanol under a fume hood, and the residual organic solvent was further removed with a rotary evaporator at low pressure. A clear solution was obtained without obvious precipitation. Both methods yielded uniform EB-CPT micelles, while the diameter of the micelles of the evaporation method was slightly larger than that of the m...

Embodiment 2

[0080] Example 2: Co-assembly of EB-CPT to PTX in a weight ratio (w / w) of 1:0.5.

[0081] 40 μL of EB-CPT (5.0 mg / mL) in methanol and 20 μL of PTX (5.0 mg / mL) in methanol were mixed and added dropwise to 2 mL of deionized water. The organic solvent methanol was mainly evaporated under a fume hood, and the remaining organic solvent methanol was further removed by a rotary evaporator under low pressure. The obtained solution was clear without obvious precipitation, indicating that the co-assembly of EB-CPT and PTX was successful. The nanoparticles co-assembled in the solution of this example are marked as "ECX (1:0.5) NVS", and the transmission electron microscope image is as follows image 3 As shown, it can be seen that the nanoparticles basically form vesicles, and although there are certain differences in the size of the vesicles, the diameter of any cross-section of each vesicle is basically below 100 nm.

Embodiment 3

[0082] Example 3: Co-assembly of EB-CPT to PTX in a weight ratio (w / w) of 1:1.

[0083] 40 μL of EB-CPT (5.0 mg / mL) in methanol and 40 μL of PTX (5.0 mg / mL) in methanol were mixed and added dropwise to 2 mL of deionized water. The organic solvent methanol was mainly evaporated under a fume hood, and the remaining organic solvent methanol was further removed by a rotary evaporator under low pressure. The obtained solution was clear without obvious precipitation, indicating that the co-assembly of EB-CPT and PTX was successful. The ECX transmission electron microscope images of nanoparticles co-assembled in solution are as follows: Figure 4 As shown, it can be seen that the nanoparticles are almost all formed into vesicles, and the size of the vesicles is relatively uniform, the diameter of each vesicle in any section is basically below 80 nm, and the diameter ratio of each dimension section does not exceed 2: 1. It is spherical as a whole.

[0084] In this example, EB-CPT a...

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Abstract

The present invention provides a nanovesicle drug, containing camptothecin (EB-CPT) and paclitaxel coupled with Evans blue; the inside of the nanovesicle has a cavity, and its wall structure is determined by the EB-CPT CPT physically wraps the paclitaxel; the nanovesicle drug is spherical, the diameter of any cross-section is not greater than 150nm, and the size ratio of any two dimensions in the three-dimensional dimension is not greater than 2:1, and the thickness of the capsule wall is between 2 and 1. 20nm; The EB-CPT structure is shown in the following formula (I), wherein, R1 is camptothecin or its derivative group from the structure shown in formula (II) or formula (III); R2 is -CH 2 ‑, or one of ‑O‑; X is S or ‑CH 2 One of ‑; n1, n2 are the number of repeating units, which are all integers of 0‑10. The nanovesicle drug of the present invention has the advantage of being more suitable for clinical application, and simultaneously has high drug loading capacity and drug loading rate. The present invention also provides a preparation method of the nanovesicle drug and its application in the preparation of cancer treatment drugs.

Description

technical field [0001] The invention belongs to the field of self-assembled nano-medicine, in particular to a nano-vesicle medicine formed by self-assembly and a preparation method and application thereof. Background technique [0002] Cancer is the second leading cause of death in the world and has become one of the main reasons threatening human survival and health. According to the statistics of the World Health Organization, there will be 19.29 million new cancer cases and 9.96 million cancer deaths globally in 2020. Cancer is responsible for about one in six deaths globally, and nearly 70% of cancer deaths occur in low- and middle-income countries. Since China is the world's most populous country, the number of new cancers and deaths in 2020 far exceed those of other countries in the world. Therefore, it has become a worldwide problem to treat cancer and improve the survival rate and quality of life of cancer patients. At present, cancer is generally treated with surg...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/54A61K47/20A61K31/4745A61P35/00B82Y5/00B82Y40/00A61K31/337
CPCA61K31/4745A61K31/337A61K9/1271A61K47/54A61K47/20A61K9/0019B82Y5/00B82Y40/00A61P35/00A61K2300/00
Inventor 陈小元吴晓明何田周子健杨清宝
Owner YANTAI LANNACHENG BIOTECHNOLOGY CO LTD
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