Application of MAPK/ERK pathway inhibitor in antagonism of skin aging and radiation-induced skin premature senility

An inhibitor, skin aging technology, applied in the medical field, can solve the problems of lack of skin anti-aging methods and no special treatment.

Pending Publication Date: 2021-07-23
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is currently a lack of satisfactory skin anti-aging methods, and there is no specific therapy that has entered the clinical stage.

Method used

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  • Application of MAPK/ERK pathway inhibitor in antagonism of skin aging and radiation-induced skin premature senility
  • Application of MAPK/ERK pathway inhibitor in antagonism of skin aging and radiation-induced skin premature senility
  • Application of MAPK/ERK pathway inhibitor in antagonism of skin aging and radiation-induced skin premature senility

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0195] Establishment of research model of premature skin aging

[0196] In this example, a premature skin aging research model was established in mice induced by local ionizing radiation. Here's how: see figure 1 A, A region of approximately 2 cm in diameter on the upper back of an adult mouse around 7 weeks old was subjected to one-time partial irradiation of γ-rays, and hair regrowth was initiated by waxing 5 days later.

[0197] Specifically, mice received partial irradiation at around 7 weeks of age (P50). Waxing (Wax) was performed five days later to induce hair regrowth. Observe the skin phenotype after the first round of hair regeneration (one round phenotype) about 28 days (4 weeks) after that, or induce the second round of hair regeneration by waxing hair removal again, and observe the second round of hair regeneration about 4 weeks later. Skin phenotype after round hair regeneration is complete (second round phenotype).

[0198] The results showed that the irradi...

Embodiment 2

[0204] Oral MAPK / ERK signaling pathway inhibitor (Trametinib) antagonizes skin aging and radiation-induced premature skin aging in vivo

[0205] In order to verify that inhibiting the MAPK / ERK signaling pathway is an effective means to antagonize skin aging and radiation-induced premature skin aging in vivo, Trametinib, an FDA-approved small molecule inhibitor of MEK1 / 2, was used as an example.

[0206] In this example, a short-term drug treatment was introduced into a skin irradiation premature aging model in order to verify the effectiveness of inhibiting the MAPK / ERK signaling pathway in antagonizing skin aging.

[0207] Test methods such as figure 2 As shown in A. Mice received one-time partial irradiation at about 7 weeks old (P50). Oral treatment with drug (Trametinib or control vehicle) was started simultaneously on the day of irradiation. The way of drug treatment is oral administration once every 3 days, a total of 5 times for a total of 15 days. Waxing was perfo...

Embodiment 3

[0216] Example 3 Applying MAPK / ERK signaling pathway inhibitor (Trametinib) to antagonize skin aging and radiation-induced premature skin aging in vivo

[0217] Repeat the method and steps of Example 2, the difference is that only oral administration is replaced by skin surface application administration, the experimental procedure outline is as follows image 3 As shown in A.

[0218] The results showed that the irradiated skin of the topical application of Trametinib group showed a significantly alleviated skin aging phenotype compared with the irradiated skin of the vehicle control treatment group, similar to the effect of the aforementioned oral administration.

[0219] Specifically include:

[0220] 1) The phenotype of decreased skin healing ability was significantly relieved ( image 3 B,3C);

[0221] 2) The depletion of skin hair follicle stem cells was significantly alleviated ( image 3 D);

[0222] 3) The phenotypes of skin and hair bleaching and hair thinning w...

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Abstract

The invention relates to an application of an MAPK / ERK pathway inhibitor in antagonism of skin aging and radiation-induced skin premature senility. The invention provides application of an MAPK / ERK pathway inhibitor, which is used for preparing a composition or a preparation for preventing or treating skin aging (or resisting skin aging). The invention also provides a method for preventing, antagonizing or delaying skin aging / premature senility by inhibiting the MAPK / ERK pathway, and a composition and a preparation for resisting skin aging.

Description

technical field [0001] The invention relates to the medical field, in particular to the application of a MAPK / ERK pathway inhibitor in antagonizing skin aging and radiation-induced premature skin aging. Background technique [0002] The aging of skin epithelial tissue (including epidermis, hair follicles, sebaceous glands, sweat glands, etc.) is the most prominent feature of human aging. The main manifestations of skin aging include wrinkle formation, decreased healing / regeneration ability, whitening / thinning hair, and atrophy of hair follicles. Epithelial stem cells (mainly including hair follicle stem cells and epidermal stem cells) in the skin are the basis for homeostasis maintenance of skin epithelial tissue and wound repair. [0003] As a lifelong self-renewing tissue, the aging of skin epithelial tissue is closely related to the exhaustion of its stem cells, but the specific molecular mechanism leading to this stem cell exhaustion is not fully understood. [0004] D...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/277A61K31/519A61K31/4184A61K31/506A61P17/18A61P17/16A61P17/00A61P17/02A61P17/14A61K8/46A61K8/49A61Q19/08A61Q17/04A61Q7/00C12Q1/6883G01N33/573
CPCA61K45/00A61K31/277A61K31/519A61K31/4184A61K31/506A61K9/0014A61P17/18A61P17/16A61P17/00A61P17/02A61P17/14A61K8/46A61K8/4953A61K8/4946A61Q19/08A61Q17/04A61Q7/00C12Q1/6883G01N33/573C12Q2600/136C12Q2600/158C12Q2600/178A61K8/49
Inventor张亮于瑶
OwnerSHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI