Applications of cyclic dinucleotide cGAMP in preparation of health products

A health food and application technology, applied in the field of biomedicine, can solve the problem of unclear mechanism of identification and clearing number, etc.

Active Publication Date: 2017-01-04

HANGZHOU XINGAO BIOTECH CO LTD

1 Cites 1 Cited by

AI-Extracted Technical Summary

Problems solved by technology

[0003] Cell-free DNA in the cytoplasm has been regarded as a potential danger signal by the host's natural immune...

Abstract

The invention belongs to the technical field of medicine, and specifically relates to applications of cyclic dinucleotide cGAMP in preparation of health products. According to the present invention, the research results show that the cyclic dinucleotide cGAMP as the human body natural immune signal pathway activator and the natural immune system enhancer can achieve the important disease preventing and body building immune defense effects of multiple virus infection prevention, tumor occurrence and development inhibition, Alzheimer disease prevention and the like by enhancing the immunity of the innate immune system; the acute animal toxicity test results show that the cGAMP does not present the significant acute toxicity, such that the cGAMP used as the endogenous second messenger capable of regulating the natural immune reaction has potential applications of virus infection prevention, virus infection resistance and tumor resistance; and the cGAMP can be used for preparing the additive of health products or special dietary.

Application Domain

Organic active ingredientsNervous disorder +3

Technology Topic

Immune defenseDisease +14

Examples

Experimental program(4)

Example Embodiment

[0007] Example 1: Preparation of cGAMP

[0008] cGAMP (cyclized-GMP-AMP) is synthesized by cyclized cGMP-AMP dinucleotide synthetase (cGAS) under the activation conditions after binding dsDNA according to the literature method. The purity is above 98%. (Pingwei Li, et al., Immunity, 2013, 39(6), 1019-1031.)

Example Embodiment

[0009] Example 2: Acute toxicity study of cGAMP

[0010] Experimental Materials

[0011] 20 ICR mice (purchased from Shanghai Slack Laboratory Animal Co., Ltd. [Experimental Animal Quality Certificate No.: SCXK (Shanghai) 2007-0005]), half male and half, weighing 18-22g, the animals are fed with pellet feed, free Eat and drink. cGAMP was prepared in Example 1, and formulated into a solution with a concentration of 200 mg/mL with physiological saline.

[0012] experimental method

[0013] ICR mice were given a single injection of 5 mg/kg cGAMP in the tail vein according to their body weight, and the toxicity and death of the mice within 14 days after administration were observed. It was found that after a single tail vein injection, the mice moved normally. Within 14 days after intravenous injection of cGAMP, the mice did not die. On the 15th day, all mice were sacrificed, dissected, and examined all organs. No obvious lesions were found.

[0014] Experimental results

[0015] The above acute toxicity test results show that the maximum tolerated dose of intravenous cGAMP MTD is not less than 5g/Kg, indicating that cGAMP has no obvious acute toxicity.

Example Embodiment

[0016] Example 3: cGAMP has the effect of immunological prevention of tumor

[0017] Experimental Materials

[0018] cGAMP was prepared in Example 1, and formulated into a solution with a concentration of 200 mg/mL with physiological saline. 20 ICR mice (purchased from Shanghai Slack Laboratory Animal Co., Ltd. [Experimental Animal Quality Certificate No.: SCXK (Shanghai) 2007-0005]), male, weighing 18-22g, the animals were fed pelleted feed, freely ingested and Drinking water. Tumor cell lines: human gastric cancer cell line MNK-45, human lung adenocarcinoma cell line A549, human colon cancer cell line Lovo, human liver cancer cell line SMMC-7721, human prostate cancer cell line PC-3, human pancreatic cancer cell line SW1990, All were purchased from the Cell Bank of the Chinese Academy of Sciences.

[0019] experimental method

[0020] Negative control, physiological saline solution; positive control, 5-fluorouracil (5-FU) anticancer reagent (dose 5mg/kg). cGAMP was injected intraperitoneally (dose 5mg/kg) for 7 days, once a day, with 8 animals in each group. Cancer cells are cultured and passaged. Cells are collected in the logarithmic phase to make the concentration 1.0×10 6 /ml cell suspension. After mice were injected with cGAMP for 7 consecutive days, 50 microliters of cancer cell suspension was injected into the armpit of the right forelimb. The negative control group (intraperitoneal injection of normal saline group), positive control group (intraperitoneal injection of 5-FU), and cGAMP group (intraperitoneal injection of cGAMP) were injected once a day for 14 consecutive days to observe the anti-tumor immune defense effects of cGAMP.

[0021] Experimental results: mice injected with cGAMP can effectively defend against tumor development. Compared with mice without cGAMP injection, the time of tumor emergence was significantly later than the control group by 3-5 days. Moreover, both 5-FU and cGAMP can significantly inhibit tumor growth, and the tumor weight 14 days after injection of cGAMP is significantly lower than that of the negative control group, indicating that cGAMP has the effect of immune prevention and anti-tumor.

PUM

Property	Measurement	Unit
Maximum tolerated dose	<= 5.0	g/kg

Description & Claims & Application Information

We can also present the details of the Description, Claims and Application information to help users get a comprehensive understanding of the technical details of the patent, such as background art, summary of invention, brief description of drawings, description of embodiments, and other original content. On the other hand, users can also determine the specific scope of protection of the technology through the list of claims; as well as understand the changes in the life cycle of the technology with the presentation of the patent timeline. Login to view more.