piRNA antisense nucleotide pharmaceutical composition and application thereof

A technology of antisense nucleotides and compositions, which is applied in the direction of drug combinations, pharmaceutical formulations, genetic material components, etc., can solve the problem that the pathogenesis of heart disease is not completely clear, and the prevention, diagnosis and treatment of heart disease cannot achieve satisfactory results. Effects and other issues, to achieve the effect of wide range of use, safe and reliable use, and friendly application environment

Active Publication Date: 2015-05-27
QINGDAO UNIV
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  • Abstract
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Problems solved by technology

At present, the pathogenesis of heart disease is not completely clear, and the prevention, diagnosis and treatment of heart...

Method used

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  • piRNA antisense nucleotide pharmaceutical composition and application thereof
  • piRNA antisense nucleotide pharmaceutical composition and application thereof
  • piRNA antisense nucleotide pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The piRNA antisense nucleotide pharmaceutical composition includes piRNA antisense nucleotides and a pharmaceutically acceptable carrier; the piRNA antisense nucleotide sequence used is shown in SEQ ID NO: 1 in the sequence listing: 5'-CCUUGGCACAUGCGCAGAUUAUUUGUUUA- 3'; the carrier is one or more of chitosan, cholesterol, nanoparticles and liposomes, preferably liposome nanoparticles. The content of the piRNA antisense nucleotide in the pharmaceutical composition is 0.5-1 gram.

Embodiment 2

[0021] Example 2, detection of piRNA expression in myocardial ischemia and cardiomyocyte apoptosis induced by hypoxia

[0022] In this embodiment, the experimental model of cardiomyocyte apoptosis is cultivated by conventional methods to cultivate the primary cardiomyocytes of rat suckling rats, cultured in a hypoxic incubator (oxygen concentration lower than 1%) for different times, extracting RNA, and detecting by real-time fluorescent quantitative PCR technology piRNA expression levels, figure 1 It is a diagram of the change of piRNA expression level in myocardial cell apoptosis process of myocardial ischemia injury and hypoxia treatment (Anoxia), wherein figure 1 A shows the expression level of piRNA in primary cardiomyocytes under hypoxia treatment; figure 1 B shows the expression level of piRNA in myocardial ischemia injury in mice; it was significantly up-regulated within 4h-8h of hypoxia treatment ( figure 1 A); The myocardial ischemia model was established by ligati...

Embodiment 3

[0023] Embodiment 3, the experiment that piRNA antisense nucleotide inhibits cardiomyocyte apoptosis

[0024] In this example, primary cultured cardiomyocytes were used as a model to transfect piRNA antisense nucleotides (the piRNA antisense nucleotide sequence is a completely reverse complementary sequence to the piRNA sequence, 5'-CCUUGGCACAUGCGCAGAUUAUUUGUUUA-3', combined with piRNA to inhibit the expression of piRNA), the transfection experiment method can be found in the aforementioned literature, after 24 hours of transfection, the treated cells were cultured in a hypoxic incubator for 3 hours to induce cell apoptosis, and trypan blue staining method was used to detect cardiomyocyte apoptosis death, see figure 2 ,in figure 2 A represents primary cardiomyocytes transfected with piRNA antisense nucleotides (anta-piRNA) to inhibit the expression of endogenous piRNA; figure 2 B represents the effect on hypoxia-induced cardiomyocyte apoptosis, and NC was transfected as a...

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PUM

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Abstract

The invention relates to a piRNA antisense nucleotide pharmaceutical composition and an application thereof. The pharmaceutical composition comprises a piRNA antisense nucleotide and a carrier, wherein the sequence of the piRNA antisense nucleotide is 5'-CCUUGGCACAUGCGCAGAUUAUUUGUUUA-3'; and the carrier is one or more of chitosan, cholesterol, nano-particles and lipidosome. The pharmaceutical composition is applied to treatment and prevention of myocardial infarction, myocardial ischemial injury and myocardial fibrosis, and is scientific and reasonable in raw material, simple in preparation technology, obvious in medicine effect, wide in application range, safe, reliable and friendly to application environment.

Description

Technical field: [0001] The invention belongs to the technical field of biomedicine, and relates to a new drug and application of endogenous non-coding small RNAs, especially a pharmaceutical composition containing piRNA antisense nucleotides and its application in preventing or treating heart disease . Background technique: [0002] Cardiovascular disease is the main threat to human health and life, and is the number one killer of human health. More than 17 million people die from cardiovascular disease in the world every year, and its mortality rate is close to the sum of all cancer mortality rates. With the improvement of human living standards and the change of diet structure, the mortality rate of cardiovascular disease is on the rise, surpassing cancer as the number one cause of death. According to the latest statistical results released recently, the prevalence of hypertension among residents aged 18 and above is 18.8%, and it is estimated that the number of patients...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P9/10A61P9/00
Inventor 王昆李培峰周露玙赵文科赵兵
Owner QINGDAO UNIV
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