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Immunotherapy nano-drug carrier, preparation method thereof, drug with carrier and preparation method of drug

A nano-drug carrier, immunotherapy technology, applied in nano-drugs, nano-technology, nano-technology, etc., can solve the problems of organ toxicity, low bioavailability, immune disorders, etc., achieve high-efficiency and durable anti-tumor immunotherapy, restore activity and cytotoxicity, restoring antitumor immune activity

Active Publication Date: 2021-04-16
NINGBO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most immunotherapeutic drugs used clinically, such as monoclonal antibodies, tyrosine kinase inhibitors, immunostimulatory drugs, etc., have poor water solubility and low bioavailability after intravenous or oral administration
Systemic administration of immunotherapy will not only bring toxic side effects to normal organs, but also may lead to immune disorders and autoimmune diseases

Method used

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  • Immunotherapy nano-drug carrier, preparation method thereof, drug with carrier and preparation method of drug
  • Immunotherapy nano-drug carrier, preparation method thereof, drug with carrier and preparation method of drug
  • Immunotherapy nano-drug carrier, preparation method thereof, drug with carrier and preparation method of drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1 (block copolymer (1))

[0044] (1) Take a 100mL round bottom flask and add 30mL of ethanol, 4.02g (30mmol) of terephthalaldehyde and 7.38g (63mmol) of 6-aminohexanol, and reflux at 85°C for 12h. After the reaction, it was placed in a refrigerator at -20°C for 4 hours, then filtered, the solid was washed with ice ethanol, and dried to obtain the product (7), a white solid, with a yield of 60.5%.

[0045] (2) ① Take a 100mL round-bottomed flask with a branch, add 4.0g (2mmol) PEG2k into it, and place it in an oil bath at 105°C to remove water under reduced pressure for 4h. ② Take a 100mL round bottom flask and add 0.72g (2.4mmol) tretinoin, 1.15g (6mmol) EDCI, 0.81g (6mmol) HOBT and 30mL dry chloroform, and stir at room temperature for 4 hours to activate tretinoin . ③Inject the activated tretinoin into ①, and react at 60°C for 72h. After the reaction, the organic phase was concentrated, precipitated three times in diethyl ether, and the solid was collecte...

Embodiment 2

[0049] Dissolve 10 mg of block copolymer (1) in 1 mL of DMSO by ultrasonic, add it dropwise to 8 mL of deionized water under stirring, stir at room temperature for 12 hours, transfer to a dialysis bag for dialysis, and centrifuge to collect the supernatant after dialysis of DMSO. liquid. After the volume was adjusted to 10 mL, vortex mixed to prepare a 1 mg / mL blank nanoparticle solution.

Embodiment 3

[0051] After ultrasonically dissolving 10 mg of block copolymer (1), 2.5 mg of sunitinib, and 2.5 mg of gemcitabine in 1 mL of DMSO, they were added dropwise to 10 mL of deionized water under stirring, stirred at room temperature for 12 hours, and then transferred to a dialysis bag for dialysis. After the DMSO was dialyzed, the supernatant was collected by filtration after centrifugation, and freeze-dried to obtain nanomedicine.

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Abstract

The invention relates to an immunotherapy nano-drug carrier, and also relates to a preparation method of the drug carrier, which comprises the following steps: (1) adding a solvent A into benzaldehyde and 6-aminohexanol, and conducting reacting to obtain a reaction solution a; (2) removing water from PEG2k, adding a condensing agent B, 1-hydroxybenzotriazole and a solvent C into tretinoin, and conducting activating to obtain a reaction solution b; (3) removing water from a product shown in a structural formula (8), then adding an organic alkali D and a solvent E, injecting acryloyl chloride, and conducting reacting to obtain a reaction solution c; and (4) removing water from a polymer shown in a structural formula (9) and a product shown in a structural formula (7) to obtain a reaction solution d, and carrying out aftertreatment on the reaction solution d to obtain a polymer shown in a structural formula (1). The invention also discloses a drug nano-material with the carrier and a preparation method of the nano-drug. The nano-drug has the advantages of high drug loading capacity, simultaneous loading of sunitinib and gemcitabine, weakly acidic stimulus-responsive degradation, targeted MDSC and the like.

Description

technical field [0001] The invention relates to a drug carrier, in particular to a drug carrier used for tumor immunotherapy, and also relates to an immunomedicine obtained from the drug carrier and a preparation method thereof. Background technique [0002] The high morbidity and mortality of cancer seriously threaten the safety of human life, and the treatment of cancer is still a global problem. In recent years, the successful cases of curing melanoma cancer patients by blocking immune checkpoint molecules (such as PD-1, PD-L1, CTLA-4, etc.) with monoclonal antibodies have brought great attention and recognition to cancer immunotherapy. [0003] The biggest flaw of current immunotherapy is that it is only effective for a small number of patients. How to effectively reverse the immunosuppressive tumor microenvironment is the key to immunotherapy. The immunosuppressive tumor microenvironment enables cancer cells to escape the recognition, monitoring and killing of immune c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K9/19A61K31/404A61K31/7068A61P35/00B82Y5/00B82Y40/00C08G65/331C08G65/332C08G65/333A61K9/107
Inventor 徐龙李民媛丁钱晶徐彩蝶
Owner NINGBO UNIV
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