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Medicine composition, and preparation method and application thereof

A composition and drug technology, applied in the field of medicine, can solve problems such as complex mechanisms

Active Publication Date: 2021-09-07
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In summary, the formation mechanism of tumors and their microenvironment is relatively complex, and it is difficult to cure malignant tumors with single therapy. This requires comprehensive regulation of tumor cells and their microenvironment, and the combination of multiple drugs can effectively control tumors. occurrence and development

Method used

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  • Medicine composition, and preparation method and application thereof
  • Medicine composition, and preparation method and application thereof
  • Medicine composition, and preparation method and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0057] 1. Preparation and characterization of gene delivery system: Cationic polymer PLL-RT, targeting molecule HA and negatively charged gene material can be assembled into nanoparticles through electrostatic interaction, and the surface morphology of gene delivery system can be characterized by particle size analyzer and scanning electron microscope appearance.

[0058] 2. Anti-tumor experiment: The co-administration of HA / PLL-RT / pSpam-1 / shPD-L1 nanoparticles and the small molecule inhibitor ibrutinib can exert the best anti-tumor effect.

[0059] 3. Degradation of tumor cell immune checkpoint experiment: HA / PLL-RT / shPD-L1 nanoparticles can efficiently reduce the level of PD-L1 protein expressed by tumor cells in vivo. The level of PD-L1 protein was detected by ELISA.

[0060] 4. Degradation of tumor extracellular matrix experiment: HA / PLL-RT / pSpam-1 nanoparticles can increase the expression of hyaluronidase in vivo, which is beneficial to the degradation of hyaluronic acid...

Embodiment 1 Embodiment 1

[0065] Embodiment 1 The preparation of embodiment 1PLL-RT gene carrier

[0066] Linear poly-α-lysine (molecular weight 15,000 Da) was dissolved in deionized water, and p-toluenesulfonyl and tert-butoxycarbonyl double-protected arginine was dissolved in DMF. Then, add EDC·HCl and HOBT, activate the reaction at room temperature for 1 hour, then slowly add the aqueous solution of PLL, and react at room temperature for 72 hours. After dialysis and freeze-drying, the product was reacted under the condition of trifluoroacetic acid for 4 hours, added with anhydrous ether to settle, vacuum-dried, dialyzed, and freeze-dried to obtain the white solid product PLL-RT.

[0067] The molar ratio of poly-α-lysine grafted to tosyl-protected arginine (Arg(Tos)) was 1:90.

Embodiment 2

[0068] Example 2 Preparation of HA / PLL-RT / pSpam-1 / shPD-L1 gene delivery system

[0069] The targeting molecule HA, cationic carrier PLL-RT, pSpam-1 and shPD-L1 were dissolved in ultrapure water to form aqueous solutions with concentrations of 0.1mg / mL, 1mg / mL, 0.2mg / mL and 0.2mg / mL, respectively. mL. Then PLL-RT, pSpam-1 and shPD-L1 were compounded in equal volumes, and the compounding ratio was 5:1:1. After vortexing for 30s, incubate at room temperature for 20 minutes, then add an equal volume of HA solution, vortex for 30s, incubate for another 20 minutes at room temperature, and finally obtain HA / PLL-RT / pSpam-1 / shPD- L1.

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Abstract

The invention relates to the technical field of medicines, in particular to a medicine composition, and a preparation method and application thereof. The medicine composition provided by the invention comprises at least two of an immune checkpoint inhibitor, a medicine for degrading the extracellular matrix of a tumor tissue and a small-molecule inhibitor, wherein the immune checkpoint inhibitor and the medicine for degrading the extracellular matrix of the tumor tissue carry related genes through a carrier and can be specifically expressed and released in a tumor microenvironment; and the purpose of treating cancers can be realized by combination with the small-molecule inhibitor. Researches show that a tumor inhibition effect can be improved by the combination of the immune checkpoint inhibitor, the medicine for degrading the extracellular matrix of the tumor tissue and the small-molecule inhibitor and is better than the tumor inhibition effect obtained by independently utilizing the above three components or utilizing any two of the above three components.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a pharmaceutical composition and its preparation method and application. Background technique [0002] Malignant tumors are one of the main killers that threaten human health and life, and their morbidity, mortality, and rejuvenation are increasing year by year. [See W.Q.Chen, R.S.Zheng, P.D.Baade, S.W.Zhang, H.M.Zeng, F.Bray, A.Jemal, X.Q.Yu, J.He, Cancer Statistics in China, 2015, Ca-CancerJ Clin 2016, 66, 115-132.] At present, the clinical treatment methods for cancer are mainly surgery, radiotherapy and chemotherapy. However, none of these traditional treatment methods can completely eliminate tumor cells and effectively control the metastasis and recurrence of tumor cells. In recent years, tumor immunotherapy was rated as the first of the top ten scientific breakthroughs in 2013 by [Science], opening a new chapter in tumor immunotherapy. [0003] Immune checkpoint blocka...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K48/00A61K38/47A61K31/519A61K47/61A61K47/62A61K47/69A61P35/00
CPCA61K45/06A61K48/005A61K38/47A61K31/519A61K47/61A61K47/62A61K47/6939A61P35/00C12Y302/01035A61K2300/00
Inventor 田华雨陈杰林琳胡莹莹郭兆培陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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