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Tumor targeted drug nanocrystal delivery system

A delivery system and tumor-targeting technology, applied in the field of pharmaceutical preparations, can solve the problems of affecting the quality of life of patients, insufficient drug efficacy, low local concentration of lesions, etc., and achieve good application potential, improved uptake, and good water dispersibility Effect

Pending Publication Date: 2021-03-02
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

For another example, in the treatment of breast cancer, the traditional radical mastectomy for breast cancer involves large surgical trauma, and the breast loss caused by surgery will significantly affect the quality of life of patients, while neoadjuvant chemotherapy can downstage the primary breast tumor and improve the survival rate. Increase the rate of breast surgery and improve the postoperative quality of life of patients ("Clinical Effects of Breast Conserving Surgery after Neoadjuvant Chemotherapy in the Treatment of Breast Cancer", "China Medical Science", 2019, No. 2: pp. 207-210)
[0004] However, there is no exclusive preparation for neoadjuvant chemotherapy currently available, and most of them use conventional preparations for postoperative chemotherapy, administered systemically, with large side effects, low local concentration in lesions, and insufficient drug efficacy

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1. Preparation and characterization of folic acid-modified phospholipid-coated paclitaxel nanocrystal delivery system

[0053] Dissolve 3 mg of paclitaxel, 4 mg of vitamin E polyethylene glycol 1000 succinate and 7.5 mg of citric acid in an appropriate amount of absolute ethanol, place in a pear-shaped bottle for rotary evaporation, evaporate the ethanol, and form a film at the bottom of the bottle, add 5 mL of bicarbonate Sodium solution (4mg / mL), shake and hydrate at room temperature, centrifuge the resulting suspension at 8000rpm for 15 minutes, discard the supernatant, collect the precipitate, disperse with pure water, and obtain a light blue opalescent The core nanocrystalline dispersion.

[0054] Weigh lecithin (1.15mg), cholesterol (0.58mg), octadecylamine (0.36mg), vitamin E macrogol 1000 succinate (0.58mg), methoxypolyethylene glycol-phosphatidyl Ethanolamine (0.70mg) and folic acid-polyethylene glycol-phosphatidylethanolamine (0.70mg), dissolved in an...

Embodiment 2

[0064] Example 2, folic acid modified phospholipid coated hydroxycamptothecin nanocrystal delivery system

[0065] Dissolve 3mg of hydroxycamptothecin, 4mg of vitamin E polyethylene glycol 1000 succinate and 7.5mg of citric acid in an appropriate amount of absolute ethanol, place in a pear-shaped bottle for rotary evaporation, evaporate the ethanol, form a film at the bottom of the bottle, add 5mL of sodium bicarbonate solution (4mg / mL), hydrated by shaking at room temperature, centrifuged the resulting suspension at 8000rpm for 15 minutes, discarded the supernatant, collected the precipitate, and dispersed it with pure water to obtain a light blue Opalescent core nanocrystalline dispersion.

[0066] Weigh lecithin (1.15mg), cholesterol (0.58mg), vitamin E macrogol 1000 succinate (0.58mg), methoxypolyethylene glycol-phosphatidylethanolamine (0.70mg) and folic acid-polyethylene glycol Diol-phosphatidylethanolamine (0.70 mg), dissolved in an appropriate amount of dichloromethan...

Embodiment 3

[0067] Embodiment 3, folic acid modified phospholipid coated curcumin nanocrystal delivery system

[0068] Dissolve 3mg of curcumin, 4mg of vitamin E polyethylene glycol 1000 succinate and 7.5mg of citric acid in an appropriate amount of absolute ethanol, place in a pear-shaped bottle for rotary evaporation, evaporate the ethanol, form a film at the bottom of the bottle, add 5mL of carbonic acid Sodium hydrogen solution (4mg / mL), hydrate by shaking at room temperature, centrifuge the resulting suspension at 8000rpm for 15 minutes, discard the supernatant, collect the precipitate, disperse with pure water, and obtain a light blue milk Light core nanocrystalline dispersion.

[0069] Weigh lecithin (1.15mg), cholesterol (0.58mg), vitamin E macrogol 1000 succinate (0.58mg), methoxypolyethylene glycol-phosphatidylethanolamine (0.70mg) and folic acid-polyethylene glycol Diol-phosphatidylethanolamine (0.70 mg), dissolved in an appropriate amount of dichloromethane, placed in a pear-...

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Abstract

The invention belongs to the field of pharmaceutical preparations, and relates to a tumor targeted drug nanocrystal delivery system and a preparation method and application thereof in pharmacy. The tumor targeted drug nanocrystal delivery system is composed of an anti-tumor drug nanocrystal core and a coating material; one or more biocompatible phospholipids, vitamin E polyethylene glycol 1000 succinate, folic acid-polyethylene glycol-phosphatidyl ethanolamine and methoxy polyethylene glycol-phosphatidyl ethanolamine are mixed according to a certain ratio, and insoluble anti-tumor drug nanocrystals are coated with the obtained mixture; the obtained tumor targeted drug nanocrystal drug delivery system can be stably dispersed in an aqueous environment, and experiments prove that the tumor targeted drug nanocrystal drug delivery system can effectively inhibit the growth of tumor cells and can effectively reduce the tumor volume after being subjected to peritumoral injection for an animalmodel. The invention provides a new preparation form capable of peritumoral injection for preoperative adjuvant chemotherapy of a solid tumor.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a tumor-targeting drug nanocrystal delivery system and a preparation method thereof, and an application in preoperative adjuvant chemotherapy for tumors. Background technique [0002] According to the latest national cancer statistics from the National Cancer Center in 2019, malignant tumors have become one of the major public health problems that seriously threaten the health of the Chinese population. The resulting deaths account for about 24% of all disease deaths, and the annual medical expenses exceed 2200. billion, the prevention and control situation is grim. Lung cancer, liver cancer, upper digestive system tumors, colorectal cancer, and female breast cancer are the main types of malignant tumors. [0003] Most of the current clinical preferred options for the above-mentioned solid tumors are surgery-based comprehensive treatment options. At present, more and mo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/68A61K47/64A61K47/61A61K47/54A61K31/337A61P35/00B82Y5/00
CPCA61K9/0019A61K31/337B82Y5/00A61K47/6935A61K47/6835A61K47/64A61K47/545A61K47/644A61K47/645A61K47/61A61P35/00
Inventor 陆伟跃刘瑜王俊黄广建
Owner FUDAN UNIV
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