CN-122005540-A - Application of kaempferol in preparing medicament for promoting cilia growth

Abstract

The present disclosure relates to the field of biological medicine, and in particular relates to an application of kaempferol in preparing a medicament for promoting cilia growth, and provides an application of kaempferol or pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs or derivatives thereof in preparing a medicament for promoting cilia growth, and a pharmaceutical composition or a pharmaceutical combination containing a therapeutically effective amount of kaempferol or pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs or derivatives thereof.

Inventors

• LI NING
• XU RUODAN
• DAI XUYAO
• CAO CAN

Assignees

• 中国中医科学院中医基础理论研究所

Dates

Publication Date

20260512

Application Date

20251107

Claims (10)

1. 1. Use of a pharmaceutical composition or pharmaceutical combination for the manufacture of a medicament for the treatment of a disease or disorder associated with cilia dysfunction; wherein the pharmaceutical composition or combination comprises a therapeutically effective amount of ambroxol and kaempferol; the cilia dysfunction-related disease or disorder is selected from any one of the following (1) - (3): (1) A primary ciliated dyskinesia is associated with the primary cilia, the primary ciliated dyskinesia is KARTAGENER syndrome; (2) A fibrotic disease, which is polycystic kidney disease, barset-Biedl syndrome, joubert syndrome, meckel-Gruber syndrome or Leber congenital amaurosis; (3) Cilia injury caused by infection with a new coronavirus.
2. 2. The use according to claim 1, wherein the molar ratio of kaempferol to ambroxol in the pharmaceutical composition or pharmaceutical combination is (1-5): 50.
3. 3. The use according to claim 1 or 2, wherein the molar ratio of kaempferol to ambroxol in the pharmaceutical composition or pharmaceutical combination is 1:50, 3:50 or 5:50.
4. 4. The use according to any one of claims 1-3, wherein the concentration of kaempferol in the pharmaceutical composition or pharmaceutical combination is 0.1-100 μm.
5. 5. The use according to any one of claims 1-4, wherein the concentration of kaempferol in the pharmaceutical composition or pharmaceutical combination is 1-3 μm or 3-5 μm.
6. 6. The use of any one of claims 1-5, wherein the concentration of kaempferol in the pharmaceutical composition or pharmaceutical combination is 1 μΜ, 3 μΜ or 5 μΜ.
7. 7. The use of any one of claims 1-6, wherein the pharmaceutical composition or pharmaceutical combination is a topical, an inhaled or an oral formulation.
8. 8. The use of any one of claims 1-7, wherein the pharmaceutical composition or pharmaceutical combination is a tablet, lozenge, capsule, pill, solution, suspension, syrup, injection, suppository, inhalation solution, inhalation powder spray, aerosol or spray.
9. 9. The use of any one of claims 1-8, wherein the pharmaceutical composition or pharmaceutical combination further comprises a pharmaceutically acceptable carrier and/or an adjunctive therapeutic agent.
10. 10. The use according to claim 9, wherein the adjunctive therapeutic agent comprises an antibiotic and/or a drug for the treatment of a systemic complication.

Description

Application of kaempferol in preparing medicament for promoting cilia growth The application relates to a divisional application, the application date of the original application is 2025, 11 and 07, the application number is 2025116313108, and the name is application of kaempferol in preparing medicines for promoting cilia growth. Technical Field The invention belongs to the field of biological medicine, and in particular relates to application of kaempferol in preparation of a medicament for promoting cilia growth. Background Cilia are microtubule-based antenna-like sensory organelles that protrude from the top of most mammalian cells for sensing extracellular signals and stimuli. Cilia consist mainly of a matrix, axillary filaments, ciliated membranes and ciliated matrix. Depending on the shaft structure, it can be divided into motor cilia ("9+2" structure) and primary cilia ("9+0" structure). The matrix required for cilia formation originates from a masterbatch, and a cilia Transition Zone (TZ) exists between the matrix and the axon, regulating the passage of proteins and membrane components into and out of the cilia. After entry of the proteins required for cilia assembly into the cilia, directional transport, including anterograde transport (via kinesin 2 and IFT-B complexes) and retrograde transport (via kinesin 2 and IFT-a complexes) of the "intra-flagellin transport" (INTRAFLAGELLAR TRANSPORT, IFT) family is primarily relied upon to promote rapid cilia elongation. Once formed, the cilia remain at a particular length. Cilia in each cell type will have a normal length range, and some congenital genetic factors (IFT, transition zone proteins and signal pathway related gene mutations) and acquired environmental factors (viral infection, environmental pollution and drug toxicity etc.) will lead to cilia loss and dysfunction, which will cause a series of diseases, collectively called fibroplasia (Ciliopathies). Primary cilia are located on the surface of most eukaryotic cells and mainly participate in signal transduction, and dysfunction of primary cilia can lead to polycystic kidney disease (Polycystic KIDNEY DISEASE, PKD), leber congenital amaurosis (Leber congenital amaurosis, LCA), barset-Biedl syndrome, joubert syndrome, meckel-Gruber syndrome and the like, and motor cilia mainly exist on the respiratory tract, ventricle, reproductive system and the like, and movement is generated through coordination of swing, such as removal of mucus by the respiratory tract cilia and movement of sperm by pushing sperm by sperm flagellum, and the dysfunction of primary cilia can lead to respiratory diseases, infertility, hydrocephalus and the like. At present, western medicine mainly aims at symptomatic support for treating fibrotic diseases, cilia cannot be repaired or regenerated, and treatment aims at relieving symptoms. For example, for respiratory tract infection, the infection is often treated by antibiotics and is assisted by expectorants, but cilia regeneration cannot be promoted, cilia clearance function is restored, and drug resistance or side effects can be possibly caused, for infertility, sperm flagella function cannot be restored by assisted reproduction technology (such as test tube infants), for hydrocephalus, ventricular cilia function cannot be restored by operation treatment (such as ventricular bypass), and the application of gene editing (such as CRISPR) in cilia disease treatment is still in experimental stage, and the problems of off-target effect, low editing efficiency, poor tissue specificity and the like exist. The traditional Chinese medicine has remarkable potential advantages in the aspects of treating and recovering cilia functions, and particularly has unique pharmacological actions in the aspects of anti-inflammatory, antioxidation, cilia power recovery and the like. In terms of anti-inflammatory aspects, such as quercetin, on the one hand, nuclear factor κB (Nuclear factor kappa-B, NF- κB), inflammatory corpuscles and interleukin-6 (interleukin-6, IL-6) driven cytokine release syndrome can be inhibited, and on the other hand, the nuclear factor-erythroid factor 2 (Nuclear factor erythroid 2-related factor 2, NRF 2) pathway can be activated to alleviate cytokine release syndrome and alleviate acute lung injury. Astragalus polysaccharides can promote high level hemagglutination inhibition titer and induction of specific antibody Immunoglobulin G (IgG), and realize bidirectional immunoregulation of cellular immunity and humoral immunity. In restoring ciliated dynamics, gypsum in e.g. Ma Xin Gault decoction can accelerate ciliated beating frequency by activating vanilloid receptor type 1 receptor (TRANSIENT RECEPTOR POTENTIAL VANILLOID, TRPV 1). Naringin can inhibit intracellular Ca 2+ level to relax tracheal smooth muscle and increase cilia swing frequency, thereby accelerating virus elimination. Hesperidin can increase the airway ciliary movement capacity and enhance the function of