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Composition and preparation method of targeting liposome-cyclic dinucleotide and application of targeting liposome-cyclic dinucleotide to anti-tumor

A technology of cyclic dinucleotides and targeted liposomes, applied in the field of biomedicine, can solve problems affecting cancer treatment, irreversible damage, side effects, etc., and achieve the effect of prolonging the metabolic cycle of cGAMP and enhancing the effect of anti-tumor treatment

Active Publication Date: 2017-05-17
HANGZHOU XINGAO BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The targeting of most anti-tumor drugs is not obvious, and they will cause side effects on normal tissues of the human body, causing irreversible damage and affecting the treatment of cancer

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Embodiment 1: Composition and preparation method of targeting liposome-cGAMP

[0023] Targeted liposomes encapsulating cGAMP drugs were prepared by reverse evaporation method and ammonium sulfate gradient method, and their properties were characterized.

[0024] 1. Liposome raw materials: lecithin (lipoid EPCs), cholesterol (CH), distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG2000) and distearoylphosphatidylethanolamine-polyethylene glycol- Folic acid (DSPE-PEG-FolicAcid) was purchased from Xi'an Ruixi Biotechnology Co., Ltd.

[0025] 2. Liposome preparation method

[0026] (1) Reverse evaporation method

[0027] (A) The phospholipid membrane material is dissolved in the organic solvent chloroform, and the ratio of the phospholipid membrane material is:

[0028] EPC : CH : DSPE-PEG2000 : DSPE-PEG2000-FA = 10 : 10 : 1 : 0.01 (molarratio); forming an organic phase solution.

[0029] (B) The cGAMP drug was dissolved in ultrapure water to form an aqueous ...

Embodiment 2

[0051] Embodiment 2: Preparation of cGAMP

[0052] cGAMP (cyclized-GMP-AMP) is catalyzed by cyclized cGMP-AMP dinucleotide synthetase (cGAS) under the conditions of activation after binding to DNA according to the literature method. The purity is above 98%. (Li P.W, et al., Immunity, 2013, 39(6), 1019-1031.)

Embodiment 3

[0053] Example 3: The anti-tumor effect of liposome-encapsulated cGAMP slow-release drug, that is, the inhibitory effect on the growth of subcutaneously transplanted tumors in animals, was tested using a tumor-bearing mouse model.

[0054] animal

[0055] Species, strains, gender, body weight, source, certificate of conformity

[0056] BALB / c ordinary mice, C57 / BL6 ordinary mice, male, body weight 16-18g, 6-8 weeks old, SPF grade, purchased from Shanghai Slack Experimental Animal Co., Ltd. [Experimental animal quality certificate number: SCXK ( Shanghai) 2007-0005].

[0057] Feeding conditions

[0058] All mice were free to forage and drink, and were kept at room temperature (23±2)°C in the Experimental Animal Center of the Military Medical University of the Chinese People’s Liberation Army. Feed and water were all processed by autoclaving, and all experimental feeding processes were SPF grade.

[0059] dose setting

[0060] Intravenous injection of mice, set up 1 dose gr...

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Abstract

The invention belongs to the technical field of medicines, and particularly discloses a composition and a preparation method of cyclic dinucleotide cGAMP (cyclic Guanosine Adenosine Monophosphate) encapsulated by a targeting liposome and application of the cyclic dinucleotide cGAMP to anti-tumor. The targeting liposome consists of lecithin, cholesterol, polyethylene glycol and the like as well as a link targeting molecule of the targeting liposome; a cGAMP slow release drug encapsulated by the targeting liposome can be used for enhancing the intensifying cell osmosis action, enhancing an immune reaction, effectively targeting drug delivery and intensifying the inhibition on the growth of multiple tumor cells. Therefore, the cGAMP encapsulated by the targeting liposome can be used for preparing an anti-tumor targeting slow release drug, and has important potential application in the field of targeting immune anti-tumor.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and specifically relates to the composition and preparation method of a targeted liposome-cyclic dinucleotide and its application in the preparation of antitumor drugs. Background technique [0002] Liposome (liposomes) is a kind of ultramicrospherical carrier preparation formed by lipid bilayer, which is a typical representative of nano drug delivery system. When amphiphilic molecules such as phospholipids are dispersed in the aqueous phase, the hydrophobic tails of the molecules gather together, and the hydrophilic heads are exposed to the aqueous phase, forming closed vesicles (vesicles) with a bilayer structure. A variety of drugs with different polarities can be encapsulated in the aqueous phase of the vesicle and the bimolecular membrane. Because the structure of liposome is similar to biological membrane, it is also called artificial biological membrane. For liposomes composed of natu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/7084A61K47/22A61P35/00A61P25/28A61P9/00A61P9/10A61P3/10
CPCA61K47/22A61K9/0002A61K9/127A61K31/7084
Inventor 谭瀛轩向道凤陆星谭相石
Owner HANGZHOU XINGAO BIOTECH CO LTD
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