CN-121991179-A - Use of active peptides for the treatment of male erectile dysfunction

Abstract

The invention provides the use of an active peptide in the treatment of male erectile dysfunction. In particular, a PDE-5 inhibitory active peptide P-C-5 is provided, which can better inhibit PDE-5 activity in human primary cavernous smooth muscle cells and increase cGMP concentration in smooth muscle cells. The mouse experiment proves that the polypeptide can better improve the capability of mice. And the polypeptide can overcome common side effects of common erectile dysfunction drugs including headache, flushing, gastric discomfort, muscle pain, back pain and nausea. The polypeptide can also be used for ED treatment in combination with other medicines, and has wide application prospect.

Inventors

• Request for anonymity
• Request for anonymity

Assignees

• 北京诺赛国际医学研究院

Dates

Publication Date

20260508

Application Date

20260331

Claims (5)

1. 1. A specific PDE5 inhibitory active peptide P-C-5 is characterized in that the amino acid sequence is shown in SEQ ID NO. 1.
2. 2. Use of the specific PDE5 inhibiting active peptide P-C-5 according to claim 1 for the preparation of a pharmaceutical composition for the treatment of male erectile dysfunction.
3. 3. The use according to claim 2, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier or excipient.
4. 4. The use according to claim 2, wherein the pharmaceutical composition is in the form of a capsule, tablet, powder, granule or suspension.
5. 5. The use of claims 2-4, further in combination with a second therapeutic agent, said second therapeutic agent being an antioxidant.

Description

Use of active peptides for the treatment of male erectile dysfunction Technical Field The present application relates to the field of biology, and more particularly to the use of active peptides in the treatment of male erectile dysfunction. Background Erectile Dysfunction (ED) refers to the inability to achieve or maintain sufficient penile erection to successfully complete intercourse, and can have a serious impact on patient confidence, ability to maintain intimate relationship, and quality of life. ED is a common disorder in men, with an overall incidence of about 50% in men over 40 years old, and with an increase in incidence with age. With changes in work and lifestyle, the pathogenic population of ED has a tendency to younger, with prevalence of up to 30% in young men. Currently, the first-line therapeutic drug for ED is a phosphodiesterase type 5 inhibitor (PDE 5 i). Phosphodiesterase 5 (PDE 5) inhibitors prolong the vasodilation mediator effect, including Nitric Oxide (NO), by blocking the breakdown of cyclic guanosine monophosphate (cGMP), resulting in vasodilation of the penis and lungs. PDE5 is mainly found in the corpora cavernosa and pulmonary blood vessels, so its main role of inhibitors is to prolong penile erection and reduce pulmonary blood vessel pressure. There are currently 4 PDE5 inhibitors approved for the treatment of erectile dysfunction, including sildenafil (vickers, 1998), tadalafil (sillisi, 2003), vardenafil (Ai Lida, 2003) and avanafil (standela, 2012). PDE5 is expressed in vascular smooth muscle in very abundant quantities, and inhibition of PDE5 limits cGMP breakdown, enhancing the vasodilation effect of the NO/cGMP pathway initiated by NO produced by endothelial or exogenous donors. During the mid 80 s of the 20 th century, the company of pyroxene developed an inhibitor of PDE5, sildenafil (derivative UK-92480 of zapst), intended for vasodilation, treatment of coronary heart disease, unexpectedly found that sildenafil was ineffective in angina pectoris, but induced penile erection enhancement in many volunteers participating in the trial. Thereafter, a great deal of research has focused on this unexpected side effect. Penile erection depends on the NO/cGMP pathway. Following sexual stimulation, NO released by non-cholinergic/non-adrenergic neurons and endothelial cells in the corpus cavernosum promotes relaxation of peripheral Smooth Muscle Cells (SMC) by increasing intracellular cGMP concentration, relaxation of smooth muscle in the corpus cavernosum and dilation of the penile artery promote dilation of sinus space, leading to blood filling and penile erection. PDE5 is the major PDE subtype in penile SMC, and therefore PDE5 inhibitors can enhance the erectile response by enhancing the effect of cGMP initiated by NO release. Sildenafil (Viagra; pyroxene) was obtained in 1998 as the first drug for oral treatment of erectile dysfunction. PDE5 inhibitors do not cause direct and sexual stimulation and only erection occurs in the case of natural stimulation, a feature which makes the drug "spontaneous" in meaning, which is also an advantage from the psychological point of view of the drug. PDE5 inhibitors are now the primary means of treating erectile dysfunction, being effective and well tolerated in more than 70% of cases. Currently, there are 7 PDE5 inhibitors (sildenafil, tadalafil, vardenafil, atorvastatin, lodinafil, me Luo Na f and udenafil) on the market, where sildenafil, vardenafil, tadalafil and atorvastatin approved by the U.S. Food and Drug Administration (FDA) are all useful in the treatment of male erectile dysfunction and there is no evidence that there is a difference in their efficacy. PDE5 inhibitors have vasodilatory properties and exert systemic hemodynamic effects, which need to be considered for vascular use in combination with other cardiovascular drugs. Among these, special care is required when combining with alpha receptor blockers, and PDE5 inhibitors are required to be disabled for nitrate (e.g., nitroglycerin or isosorbide nitrate) treatment. The combination of these 2 drugs with PDE5 inhibitors can cause sustained vasodilation and are extremely dangerous. However, increased PDE5A expression in blood vessels was observed in the rat nitrate tolerance model, and inhibition of PDE with zaprinast and vinpocetine, respectively, was effective in reversing this tolerance, indicating that up-regulation of PDE is associated with nitrate tolerance. The potential use of PDE5 inhibitors to limit nitrate tolerance remains to be evaluated in clinical trials. Sildenafil is not used in patients with severe cardiovascular diseases, such as angina or severe heart failure, and hypotension (blood pressure below 90/50 mmHg), severe liver damage, retinitis pigmentosa, and patients with history of stroke or myocardial infarction are forbidden. Therefore, based on the side effects of the existing PDE5 inhibitors, the development of new PDE5 inhibitors with little toxic sid