阅读说明：本技术 pifithrin-α在制备放疗辐照后促进皮肤伤口愈合的药物中的应用 (Application of pifithrin-alpha in preparation of medicine for promoting skin wound healing after radiotherapy irradiation ) 是由 孙鹏 张亮 王国栋 赵云富 陈潇卿 张斌 于 2019-09-18 设计创作，主要内容包括：本发明涉及医药技术领域,具体是p53抑制剂pifithrin-α在制备放疗辐照后促进皮肤伤口愈合的药物中的应用。本发明提供了p53抑制剂pifithrin-α的一种新的应用,其可以有效地促进辐照后皮肤伤口的愈合,这对辐照后皮肤伤口的愈合具有重大意义；pifithrin-α是可以人工合成的一种生物小分子,因此成本低廉,可以大量生产。(The invention relates to the technical field of medicines, in particular to application of a p53 inhibitor pifithrin-alpha in preparation of a medicine for promoting skin wound healing after radiotherapy irradiation. The invention provides a new application of p53 inhibitor pifithrin-alpha, which can effectively promote the healing of skin wounds after irradiation and has great significance for the healing of the skin wounds after irradiation; the pifithrin-alpha is a biological small molecule which can be artificially synthesized, so the cost is low and the pifithrin-alpha can be produced in large quantities.)

application of pifithrin-alpha in preparation of medicines for promoting skin wound healing after radiotherapy irradiation.

2. The use of an inhibitor of p53 in the manufacture of a medicament for promoting healing of skin wounds following radiation therapy exposure to Co 53 wherein said radiation therapy exposure is Co⁶⁰And (4) irradiating gamma rays.

Application of pifithrin-alpha in preparation of medicine or reagent for promoting skin fibroblast proliferation after radiotherapy irradiation.

4. The use of the p53 inhibitor for the manufacture of a medicament or agent for promoting proliferation of dermal fibroblasts following radiation therapy exposure to Co, wherein said radiation therapy exposure is⁶⁰And (4) irradiating gamma rays.

5. A pharmaceutical preparation for promoting skin wound healing after radiotherapy irradiation contains pifithrin-alpha as active ingredient.

6. The pharmaceutical formulation of claim 5, wherein said radiation therapy radiation is Co⁶⁰And (4) irradiating gamma rays.

7. The pharmaceutical preparation of claim 5, wherein the pharmaceutical preparation for promoting skin wound healing after radiation treatment further comprises a pharmaceutically acceptable carrier or adjuvant.

Technical Field

The invention relates to the technical field of medicines, in particular to application of a p53 inhibitor pifithrin-alpha in preparation of a medicine for promoting skin wound healing after radiotherapy irradiation.

Background

Radiotherapy is a therapeutic method for killing tumor cells by using the effect of Ionizing Radiation (IR), and plays an important role in the treatment of head and neck malignant tumors. According to literature statistics, about 5492200 new head and neck cancer cases are increased every year worldwide, and more than 50% of patients need to receive radiotherapy during the treatment process. Clinically, besides the therapeutic effect of radiotherapy, the frequently-induced complications are acute skin damage (mainly manifested by erythema, desquamation, hair loss, ulcer and the like) and skin wound healing disorder after surgical operation. The latter is mainly manifested by delayed healing, disunion or repeated ulceration of the local operation wound, increasing the probability of infection and tissue necrosis at the wound site, and finally turning into radiation skin ulcer.

Pifithrin-alpha (p53 inhibitor) was found to have the ability to reduce p53 expression by chemical libraries based on a cell readout system. Pfta can affect the p53 pathway at multiple points, and can also act by targeting multiple factors that act synergistically with p53 function. Experiments have shown that it works by interfering with the accumulation of p53 in the nucleus. (KOMAROVAE A, NEZANOV N, KOMAROV P G, et al, p53 inhibitor Pi fisher alpha can supply shock and glucose short signaling pathways [ J ]. J Biol Chem,2003.278(18):15465-8. doi: 10.1074/jbc. C300011200).

At present, no report exists on the application of the p53 inhibitor pifithrin-alpha in the healing of skin wounds after irradiation.

Disclosure of Invention

The invention aims to provide a new application of a p53 inhibitor pifithrin-alpha.

In a first aspect of the invention, the application of pifithrin-alpha in the preparation of a medicament for promoting the healing of skin wounds after radiation treatment irradiation is provided.

Through a large number of experimental researches, the present invention surprisingly discovers that pifithrin-alpha has the effect of accelerating the recovery of the skin wound after irradiation.

In-vivo experiments prove that the pifithrin-alpha can accelerate the proliferation of long-term passage cells after irradiation after blocking a p53 channel, and has no influence on the proliferation of normal cells.

In the present invention, the pifithrin-alpha is a small biological molecule that can be artificially synthesized, and is commercially available from sigma or seleck.

Further, the radiotherapy irradiation of the cells is Co⁶⁰Gamma ray irradiation; the total radiation dose is 10Gy, and the radiation irradiation of the mice is Co⁶⁰Gamma ray irradiation; the total radiation dose was 5 Gy.

In a second aspect of the invention, the application of pifithrin-alpha in preparing a medicament or a reagent for promoting the proliferation of skin fibroblasts after radiation treatment irradiation is provided.

In a third aspect of the invention, a pharmaceutical preparation for promoting skin wound healing after radiation therapy irradiation is provided, wherein the active ingredient is pifithrin-alpha.

Furthermore, the pharmaceutical preparation for promoting skin wound healing after radiotherapy irradiation also comprises a pharmaceutically acceptable carrier or auxiliary material.

The invention has the advantages that:

1. The invention provides a new application of p53 inhibitor pifithrin-alpha, which can effectively promote the healing of skin wounds after irradiation. The method has great significance for healing of skin wounds after irradiation;

2. The pifithrin-alpha is a biological small molecule which can be artificially synthesized, so the cost is low and the pifithrin-alpha can be produced in large quantities.

drawings

FIG. 1 is a photograph of the p53 inhibitor pifithrin-alpha promoting proliferation of dermal fibroblasts in mice after long-term irradiation. A picture shows that the content of p53 pathway downstream protein p21 is obviously reduced after p53 inhibitor pifithrin-alpha acts, which indicates that p53 inhibitor pifithrin-alpha acts well; b is a p21 protein expression quantitative result after p53 inhibitor pifithrin-alpha acts; and the C picture shows that the cell proliferation rate of the 3 rd generation mouse embryo fibroblast is 1 day (24h) after the P53 inhibitor pifithrin-alpha is irradiated, and the cell proliferation rate of the pifithrin-alpha acting group is obviously changed compared with that of a control group (P is less than 0.05).

FIG. 2. A: the wound was photographed at each time point and the results were obtained; b: and comparing the results of the histogram of the wound area at each time point.

Detailed Description

The following detailed description of the present invention will be made with reference to the accompanying drawings.

The experimental procedures, for which specific conditions are not noted in the following examples, are generally carried out under conventional conditions, or under conditions recommended by the manufacturer.