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Pharmaceutical composition nano-system for anti-tumor immunotherapy

A technology of anti-tumor immunity and composition, which is applied in the field of medicine, can solve problems such as literature and patents, and achieve the effects of reducing toxic and side effects, good tumor targeting, and good synergistic effect

Active Publication Date: 2019-03-26
南京从一医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Perfluorocarbon has good gas solubility, making it a good carrier medium for respiratory gas. It was first used in blood substitutes (PFC emulsion) and widely used in the medical field, but the main medical use is still limited to the oxygen supply category. Inside
[0006] So far, there are no records or reports on the literature and patents of the pharmaceutical composition nanosystem based on perfluorocarbons and immune checkpoint inhibitors in the aspect of sensitizing anti-tumor immunotherapy

Method used

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  • Pharmaceutical composition nano-system for anti-tumor immunotherapy
  • Pharmaceutical composition nano-system for anti-tumor immunotherapy
  • Pharmaceutical composition nano-system for anti-tumor immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1: Preparation scheme of pharmaceutical composition nanosystem (PFC@PD-L1@Albumin) loaded with perfluorocarbon and PD-L1 checkpoint inhibitor

[0036] Measure an appropriate amount of albumin stock solution, prepare albumin solution (10g / 200mL) with distilled water and place it in an ultrasonic vial, pre-mix with a 1mL pipette gun, then add 1mL perfluoroiodobutane and 500μL ethanol (analytical grade) , and finally add 3 mg anti-PD-L1 antibody, and mix well by pipetting. The nanoemulsion system obtained above was placed in an ice-water bath, and a cell sonicator was used to sonicate for 3 cycles (ultrasonic power 300W), and each cycle was 2 minutes. At the end of each sonication, place the preparation in a water bath at 4° C. to cool for 1-2 minutes. Finally, the sample was centrifuged at 3500rpm for 3min, and the supernatant was taken as the prepared pharmaceutical composition nanosystem (PFC@PD-L1@Albumin). figure 1 .

Embodiment 2

[0037] Example 2: Preparation scheme of a separate perfluorocarbon albumin preparation (PFC@Albumin)

[0038] Measure an appropriate amount of albumin stock solution, prepare albumin solution (10g / 200mL) with distilled water and place it in an ultrasonic vial, pre-mix with a 1mL pipette gun, then add 1mL perfluoroiodobutane and 500μL ethanol (analytical grade) , fully mixed by pipetting. The nanoemulsion system obtained above was placed in an ice-water bath, and a cell sonicator was used to sonicate for 3 cycles (ultrasonic power 300W), and each cycle was 2 minutes. At the end of each sonication, place the preparation in a water bath at 4° C. to cool for 1-2 minutes. Finally, the sample was centrifuged at 3500 rpm for 3 min, and the supernatant was obtained as the prepared separate perfluorocarbon albumin preparation (PFC@Albumin).

Embodiment 3

[0039] Example 3: Biodistribution of pharmaceutical composition nanosystems in tumor-bearing mice

[0040]Male Balb / c mice with a body weight of about 18-22 g were selected to establish a colon cancer (CT26) subcutaneous transplantation model, and the IR775 package was loaded into the pharmaceutical composition nanosystem to track the distribution of nanoparticles in the tumor-bearing mice. One week after the mouse tumor was inoculated, the nanosystem (0.1mL / 10g) of the pharmaceutical composition loaded with IR775 was injected into the tail vein, and the time points of 1h, 10h, 24h, 48h and 72h were taken after administration, and 2% pentobarbital sodium The mice were anesthetized with the solution, and bioluminescent imaging was performed on the mice in each group to track the biodistribution of the drug composition nanosystem in vivo through small animal live imaging, see figure 2 . The results show that the pharmaceutical composition nanosystem can effectively target and ...

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Abstract

The invention discloses a pharmaceutical composition nano-system for anti-tumor immunotherapy, and particularly, a therapeutically effective amount of one or more perfluorocarbon compounds and one ormore immune checkpoint inhibitors are wrapped in an albumin shell as active ingredients. It is proved by experiments that a pharmaceutical composition can increase the vascular permeability by openinga tumor vascular barrier, promotes the infiltration of immune T cells in tumors, enhances the killing activity of tumor-associated T cells at the same time, increases the expression level of toxic killer factors such as IFN-gamma, TNF-alpha and IL-6, exerts a synergistic effect of anti-tumor immunity, and provides a solution to the problem of low patient response rate in the clinical single druguse process of the immune checkpoint inhibitors.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a pharmaceutical composition nanosystem for anti-tumor immunotherapy, in particular to the pharmaceutical composition nanosystem, which can increase the permeability of blood vessels by opening the tumor blood vessel barrier, promote the tumor infiltration of immune cells, and induce anti-tumor Immune response, synergistic sensitization and anti-tumor efficacy. Background technique [0002] At present, cancer is still one of the biggest problems threatening human health. Every year, more than 14 million people worldwide suffer from cancer, and more than 8 million people die from cancer. With the increasing incidence and mortality of malignant tumors, the need for malignant tumor treatment getting bigger. Surgery, radiotherapy, chemotherapy and targeted therapy are currently the main treatment methods for tumors, but these methods have more or less serious side effects, drug resistance and ...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/42A61K47/18A61K47/06A61K39/395A61P35/00
CPCA61K39/3955A61P35/00A61K9/5123A61K9/5169
Inventor 吴锦慧张宝丽王浩然陈维生
Owner 南京从一医药科技有限公司
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