Study on the Effectiveness of Tranilast in the Treatment of Medium to Large Volume Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is one of the most common urinary and reproductive system diseases in elderly men. The incidence of histological BPH in males aged 60 and above is over 50%, reaching as high as 83% at the age of 80. About 50% of BPH cases can lead to moderate to severe lower urinary tract symptoms (LUTS), and even serious complications such as hydronephrosis, which greatly affects the quality of life and health of patients, and also brings heavy social and medical burdens.

One of the important risk factors for the clinical progression of BPH is prostate volume. The risk of acute urinary retention and surgical intervention in BPH patients increased significantly with the increase of prostate volume. Medium to large volume prostate (prostate volume ≥ 60mL) is more likely to cause bladder outlet obstruction and severe hematuria, and surgical treatment is relatively difficult, with significantly increased surgical difficulty and complications. Therefore, controlling prostate volume is crucial in the treatment of benign prostatic hyperplasia.

At present, the commonly used drugs for the treatment of large volume prostate hyperplasia in clinical practice are 5 α - reductase inhibitors and α - receptor antagonists. The mechanism of action of 5 α - reductase inhibitors (such as finasteride, aprepit, etc.) is to inhibit the production of dihydrotestosterone to reduce prostate volume. However, about 40% of patients have poor reactions to these drugs, and long-term use of these drugs can lead to adverse reactions such as impaired sexual function (erectile dysfunction, decreased libido, etc.), breast discomfort, and rash. The mechanism of action of alpha receptor antagonists (such as doxazosin, tamsulosin, etc.) is to reduce urethral smooth muscle pressure and alleviate LUTS symptoms caused by BPH, but they cannot intervene in the continuous increase of prostate volume.

Quinilast is a highly effective and safe stabilizer for mast cells, TGF - β pathway inhibitor, and anti-inflammatory agent. It has a stabilizing effect on the cell membrane of mast cells and eosinophils, preventing their degranulation and inhibiting the release of histamine and 5-hydroxytryptamine allergens. It has a significant inhibitory effect on IgE antibody induced skin allergies and experimental asthma in rats. Quinilast can also inhibit collagen synthesis in fibroblasts and is currently widely used to treat allergic diseases and scars. After oral administration, the drug is rapidly absorbed in the gastrointestinal tract, with a peak plasma concentration time of 2-3 hours. It is widely distributed in all organs and tissues, with the highest concentration in the bronchi and lungs, followed by the liver, kidneys, and small intestine. The plasma half-life is 5-8.6 hours, and the blood drug concentration significantly decreases by 24 hours, making it difficult to detect after 48 hours. Metabolized in the liver, after administration, it is mainly excreted from the urine. Metabolites in the body include the demethylation product of tranilast at position 4, as well as the combination of sulfuric acid and glucuronic acid. Previous studies have confirmed that the TGF - β pathway is one of the important pathways that promote the occurrence and development of BPH. Our research confirms that the phenomenon of endothelial mesenchymal transition is an important factor in promoting the progression of BPH.

TGF - β 1 and VEGFA secreted by mast cells are important cytokines that promote endothelial mesenchymal transition in BPH, and stabilizing mast cells can inhibit endothelial cell to mesenchymal transition. The investigators confirmed through animal experiments that oral administration of tranilast (100mg/kg/d, n=10) to BPH mice for 30 consecutive days resulted in a decrease in endothelial mesenchymal transition and degree of BPH in the prostate of the mice. There was no statistically significant difference in body weight compared to the control group, and no mice died. Therefore, the investigators believe that tranilast has a promising application prospect in the treatment of BPH.