CN-121987636-A - Application of RDB in preparation of pseudomonas aeruginosa quorum sensing inhibitor and skin wound repair drug

Abstract

The invention discloses an application of RDB in preparing pseudomonas aeruginosa quorum sensing inhibitors and skin wound repair medicines. The invention discovers and verifies that RDB can inhibit the transcriptional activity of quorum sensing regulatory factors LasR, qscR, rhlR and PqsR of pseudomonas aeruginosa while not inhibiting the growth of pseudomonas aeruginosa, inhibit the formation of a biological film, the secretion of virulence factors and the generation of virulence, and simultaneously promote the phagocytosis and the clearance of macrophages on pseudomonas aeruginosa, inhibit inflammatory reaction caused by virulence factor Lipopolysaccharide (LPS), promote the repair of skin wound surfaces of mice and inhibit the infection of wound surfaces of pseudomonas aeruginosa. RDB is used for preparing pseudomonas aeruginosa quorum sensing inhibitors and skin wound repair medicaments, and is beneficial to solving the treatment problem of pseudomonas aeruginosa infection of skin wound.

Inventors

• LI DANDAN
• LI JUNXI
• ZHENG ZHIXIN
• BAO BAOQUAN
• LI HUIYAN
• NIU WENXIN

Assignees

• 天津中医药大学

Dates

Publication Date

20260508

Application Date

20260310

Claims (10)

1. Use of rdb in the preparation of an inhibitor of quorum sensing in pseudomonas aeruginosa.
2. 2. Use of a pharmaceutical composition comprising RDB and a pharmaceutically acceptable salt, carrier or excipient thereof in the manufacture of an inhibitor of quorum sensing in pseudomonas aeruginosa.
3. 3. The use of RDB according to claim 1 for the preparation of an inhibitor of pseudomonas aeruginosa quorum sensing, wherein said inhibitor is LasR, qscR, rhlR and PqsR pathway inhibitor.
4. 4. The use of RDB according to claim 1 for the preparation of an inhibitor of quorum sensing in pseudomonas aeruginosa, wherein said inhibitor is a biofilm formation inhibitor.
5. 5. The use of RDB according to claim 1 for the preparation of a quorum sensing inhibitor of pseudomonas aeruginosa, wherein the pseudomonas aeruginosa is wild type pseudomonas aeruginosa PAO1 or multidrug resistant pseudomonas aeruginosa MDR1.
6. Application of RDB in preparing skin wound repair medicine.
7. 7. Use of a pharmaceutical composition comprising RDB and a pharmaceutically acceptable salt, carrier or excipient thereof in the manufacture of a medicament for repairing a skin wound.
8. 8. The use of RDB according to claim 6 for the preparation of a medicament for skin wound repair, wherein RDB promotes phagocytosis and clearance of pseudomonas aeruginosa by macrophages.
9. 9. The use of RDB according to claim 6 for the preparation of a medicament for skin wound repair, wherein RDB inhibits inflammatory response caused by pseudomonas aeruginosa virulence factor LPS.
10. 10. The use of RDB according to claim 6 for the preparation of a medicament for skin wound repair, wherein RDB promotes healing of a skin wound in a mouse and inhibits pseudomonas aeruginosa infection of a skin wound in a mouse.

Description

Application of RDB in preparation of pseudomonas aeruginosa quorum sensing inhibitor and skin wound repair drug Technical Field The invention relates to the technical field of biological medicines, in particular to application of (R) -6' -debromination Ma Kaxin B (abbreviated as RDB) in preparation of pseudomonas aeruginosa quorum sensing inhibitor and skin wound repair medicine. Background Skin is the organ with the largest surface area of the human body, and skin injury caused by burns, scalds, wounds and the like seriously breaks the integrity of the skin, so that the bottom tissues are exposed to microbial contamination, thereby causing wound infection and causing delayed healing and deep damage of the integrity of tissue and organs. If the treatment is not in time, local wound infection can develop into systemic infection, sepsis, multiple organ failure and even death, and is a serious public health problem facing the clinic at present. Pseudomonas aeruginosa (Pseudomonas aeruginosa, PA) is one of the most common pathogenic bacteria for skin wound infection, and can affect various stages of inflammation, proliferation, remodeling and the like of wound repair process. At present, the treatment of wound surface pseudomonas aeruginosa infection is mainly based on local and systemic antibiotic treatment and is assisted with debridement and various tissue regeneration therapies in clinic. However, due to the generalization and overuse of antibiotics, pseudomonas aeruginosa can rapidly develop resistance to various types of antibiotics. Research shows that the quorum sensing inhibitor for pseudomonas aeruginosa does not directly kill bacteria, but is a strategy for reducing bacterial virulence by inhibiting the quorum sensing system to block communication among bacteria under the condition of not interfering with bacterial growth, has smaller selective pressure on bacterial growth, and can inhibit pseudomonas aeruginosa infection and simultaneously has smaller drug resistance. However, up to now, quorum sensing inhibitors have not been marketed as single drug batches. The application of the RDB in pseudomonas aeruginosa quorum sensing inhibitors and skin wound repair drugs is not reported. Disclosure of Invention In order to overcome the defects of the prior art, the main purpose of the invention is to provide the application of RDB in the preparation of pseudomonas aeruginosa quorum sensing inhibitor and skin wound repair drugs, and solve the problem of the pseudomonas aeruginosa drug resistance to various antibiotics. In order to achieve the purpose of the invention, the technical scheme adopted by the invention comprises the following steps: use of RDB in the preparation of an inhibitor of quorum sensing in pseudomonas aeruginosa. Use of a pharmaceutical composition comprising RDB and pharmaceutically acceptable salts, carriers or excipients thereof in the manufacture of an inhibitor of quorum sensing in pseudomonas aeruginosa. The inhibitors are LasR, qscR, rhlR and PqsR pathway inhibitors. The inhibitor is a biofilm formation inhibitor. The pseudomonas aeruginosa is wild pseudomonas aeruginosa PAO1 or multidrug resistant pseudomonas aeruginosa MDR1. Application of RDB in preparing skin wound repair medicine is provided. Use of a pharmaceutical composition comprising RDB and pharmaceutically acceptable salts, carriers or excipients thereof in the manufacture of a medicament for the repair of skin wounds. RDB promotes phagocytosis and clearance of pseudomonas aeruginosa by macrophages. RDB inhibits inflammatory response by the pseudomonas aeruginosa virulence factor LPS. RDB promotes healing of the skin wound surface of the mice and inhibits pseudomonas aeruginosa infection of the skin wound surface of the mice. Compared with the prior art, the invention has the beneficial effects that: the invention discovers and verifies that RDB can inhibit the transcriptional activity of quorum sensing regulatory factors LasR, qscR, rhlR and PqsR of pseudomonas aeruginosa while not inhibiting the growth of pseudomonas aeruginosa, inhibit the formation of a biological film, the secretion of virulence factors and the generation of virulence, and simultaneously promote the phagocytosis and the clearance of macrophages on pseudomonas aeruginosa, inhibit inflammatory reaction caused by virulence factor Lipopolysaccharide (LPS), promote the repair of skin wound surfaces of mice and inhibit the infection of wound surfaces of pseudomonas aeruginosa. RDB is used for preparing pseudomonas aeruginosa quorum sensing inhibitors and skin wound repair medicaments, and is beneficial to solving the treatment problem of pseudomonas aeruginosa infection of skin wound. Drawings FIG. 1.10. Mu.M RDB effect on Pseudomonas aeruginosa production; FIG. 2 shows that RDB inhibits quorum sensing activity of Pseudomonas aeruginosa at low concentration, (A) patterns of interaction of 3OC12-HSL and (B) RDB with LasR, (C) patterns of interaction of H