Taxane medicines albumin nanoparticle preparation for injection and preparation method thereof

A technology of albumin nanoparticles and taxanes, which is applied in the field of taxane drug albumin nanoparticle preparations for injection and its preparation, which can solve the problem of nano-preparations that have not been seen yet, require frequent administration, and easily cause complications To achieve good clinical application prospects, improve anti-tumor effect, and reduce dosage

Active Publication Date: 2014-08-06
FUDAN UNIV
View PDF18 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, although taxanes have good anti-tumor effects, the treatment practice shows that they still have the following defects: (1) Because the drug is poorly soluble in water (paclitaxel has a solubility of 0.0005mg / mL in water at room temperature, docetaxel Almost insoluble in water)), clinically used injections all need to add a large amount of surfactants, such as paclitaxel using CremophorEL to help dissolve, docetaxel using Tween 80 to help dissolve, etc., resulting in relatively large toxic side effects of the injection in clinical application, easy to Cause complications, such as allergic reaction, bone marrow suppression, neurotoxicity, cardiovascular toxicity, hair loss, etc.; (2) Due to the rapid distribution and metabolism of the drug after entering the body, the blood drug concentration decreases rapidly, which requires frequent administration and long-term (3) Since the drug is a cytotoxic drug and has no targeting, the drug is distributed throughout the body after conventional injection administration, resulting in systemic toxic and side effects. However, there is no attempt to modify its structure to reduce adverse reactions. Greater progress
[0013] So far, the basic and applied basic research on taxane drugs has mainly focused on their targeting research as a model drug and the research on drug combination. Literature report

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Taxane medicines albumin nanoparticle preparation for injection and preparation method thereof
  • Taxane medicines albumin nanoparticle preparation for injection and preparation method thereof
  • Taxane medicines albumin nanoparticle preparation for injection and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1, the prescription process of paclitaxel albumin nanoparticles

[0041] Table 1 The ratio of each component in the formulation of paclitaxel-loaded albumin nanoparticles (mg)

[0042]

[0043]

[0044] Dissolve paclitaxel in prescriptions 1 to 30 in Table 1 in an appropriate amount of ethanol or other suitable solvents, dissolve phospholipids in an appropriate amount of dichloromethane, and mix the two as an oil phase; dissolve albumin and antioxidants in an appropriate amount of In ionic water (water phase), drop the oil phase into the magnetically stirred water phase at room temperature or in an ice-water bath, and continue to stir for a certain period of time, then remove ethanol and dichloromethane by rotary evaporation in a water bath at 40°C to obtain paclitaxel-loaded Albumin nanoparticles.

Embodiment 2

[0045] Embodiment 2, the prescription process of docetaxel albumin nanoparticles

[0046] Table 2 Proportion of each component in the formulation of albumin nanoparticles loaded with docetaxel (mg)

[0047]

[0048]

[0049] Dissolve docetaxel in prescriptions 1 to 30 in Table 2 in an appropriate amount of ethanol or other suitable solvents, dissolve phospholipids in an appropriate amount of dichloromethane, and mix the two as an oil phase; dissolve albumin and antioxidants in an appropriate amount In deionized water (water phase), drop the oil phase into the magnetically stirred water phase at room temperature or in an ice-water bath, and continue stirring for a certain period of time, then remove ethanol and dichloromethane by rotary evaporation in a water bath at 40°C, and then get more Albumin nanoparticles of paclitaxel.

Embodiment 3

[0050] Example 3. Pharmacodynamic test of albumin nanoparticles loaded with paclitaxel on subcutaneous non-small cell lung cancer

[0051] Tumor cells: human non-small cell lung cancer A549 cells (purchased from Shanghai Cell Bank, Chinese Academy of Sciences), cultured in DMEM medium containing 10% fetal bovine serum.

[0052] Animals: Balb / c nude mice, 4 weeks old, male. There were 6 nude mice in each group of test group and negative control group.

[0053] Inoculation of tumor cells: The right axillary subcutaneous inoculation model was adopted, and vigorously growing A549 cells were taken under aseptic conditions, the cells were digested, centrifuged and resuspended to a cell suspension of about 2.0E7 / ml, and 0.1 ml cancer cell suspension.

[0054] The tumor volume and tumor inhibition rate were calculated by the same method as before.

[0055] Each group was administered for two weeks according to the dosage regimen in Table 3.

[0056] The dosing regimen of each expe...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
particle diameteraaaaaaaaaa
Login to view more

Abstract

The invention belongs to the field of medicinal preparation, and relates to taxane medicines albumin nanoparticle preparation for injection and a preparation method of the preparation. According to the invention, the albumin nanoparticle preparation is prepared by combining the albumin with the taxane medicines to form the albumin nanoparticles by dispersing and stabilizing with the phospholipid. According to the invention, the strengthened osmosis and retention effect on the tumors by the nanoparticles are utilized, and more medicines are passively targeted and concentrated on the tumor tissues so as to improve the antitumor effect; simultaneously, due to the fact that the bioavailability in the injection way is high and the soluble albumin nanoparticle preparation for injection exists passive targeting, the administration dose can be greatly reduced, so that the medicinal concentration on the non-target parts can be effectively reduced, the toxic and side effects of the medicines can be reduced, and the good clinical application prospect can be implemented. The preparation is convenient in preparation method and is suitable for industrial mass production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an albumin nanoparticle preparation of taxane drugs for injection and a preparation method thereof. Background technique [0002] In recent years, the incidence of tumor has risen sharply, and its treatment is difficult and its mortality rate is high. It has become the second leading cause of human death. According to reports, about 6 million people die of malignant tumors in the world every year, among which about 4.5 million cancer patients in China, the mortality rate exceeds 30%, which has become a serious social problem. At present, surgery, chemotherapy, and radiotherapy are usually used in the clinical treatment of malignant tumors; for early-stage tumors, surgical resection combined with other therapies can often achieve better therapeutic effects; The development of the disease is accompanied by severe immune system suppression or toxic side effects, and it is d...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K31/337A61K47/42A61K47/24A61P35/00
Inventor 高会乐蒋新国庞志清
Owner FUDAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products