Use of active peptides in the treatment of male erectile dysfunction

Abstract

The application provides application of an active peptide in treatment of male erectile dysfunction. Specifically, a PDE-5 inhibiting active peptide P-C-5 is provided, the active peptide can better inhibit the activity increase of PDE-5 in human primary cavernous smooth muscle cells, and can increase the cGMP concentration in the smooth muscle cells. In a mouse experiment, it is proved that the polypeptide can better improve the sexual ability of the mouse. Moreover, the polypeptide can overcome common side effects of common erectile dysfunction drugs, including headache, flushing, stomach discomfort, muscle pain, back pain and nausea. The polypeptide can also be used in combination with other drugs for ED treatment, and has a wide application prospect.

Description

Technical Field

[0001] This application relates to the field of biology, and more specifically to the application of bioactive peptides in the treatment of male erectile dysfunction. Background Technology

[0002] Erectile dysfunction (ED) refers to the inability to achieve or maintain an erection sufficient for successful sexual intercourse, which can severely impact a patient's self-confidence, ability to maintain intimate relationships, and quality of life. ED is a common urological condition, with an overall incidence rate of approximately 50% in men over 40 years of age, and the incidence increases with age. With changes in work and lifestyle, the incidence of ED is trending younger, with a prevalence rate as high as 30% in young men. Currently, the first-line treatment for ED is a phosphodiesterase type 5 inhibitor (PDE5i).

[0003] Phosphodiesterase 5 (PDE5) inhibitors prolong the action of vasodilatory mediators, including nitric oxide (NO), by blocking the breakdown of cyclic guanosine monophosphate (cGMP), thereby leading to vasodilation in the penis and lungs. PDE5 is primarily found in the corpora cavernosa of the penis and pulmonary vessels, so the main effects of its inhibitors are to prolong penile erection and reduce pulmonary vascular pressure. Currently, four PDE5 inhibitors are approved for the treatment of erectile dysfunction: sildenafil (Viagra, 1998), tadalafil (Cialis, 2003), vardenafil (Levitra, 2003), and avanafil (Standra, 2012). PDE5 is highly expressed in vascular smooth muscle; inhibiting PDE5 limits cGMP breakdown and enhances the vasodilatory effects of the NO / cGMP pathway induced by NO produced by endothelial or exogenous donors. In the mid-1980s, Pfizer developed a PDE5 inhibitor, sildenafil (a derivative of zaplastate, UK-92480), intended for vasodilation and treatment of coronary artery disease. Unexpectedly, sildenafil was found to be ineffective against angina, but it induced enhanced penile erection in many trial participants. Subsequent research 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 (SMCs) by increasing intracellular cGMP concentration. The relaxation of smooth muscle within the corpus cavernosum and the dilation of penile arteries promote the expansion of sinus tract spaces, leading to blood filling and penile erection. PDE5 is the major PDE subtype in penile SMCs; therefore, PDE5 inhibitors can enhance the erectile response by enhancing the effects of cGMP induced by NO release. In 1998, sildenafil (Viagra®; Pfizer) was approved as the first oral medication for the treatment of erectile dysfunction. PDE5 inhibitors do not cause direct or sexual stimulation; erections only occur in conjunction with natural stimuli. This characteristic gives the drug a "spontaneous" quality, which is also a psychological advantage. Currently, PDE5 inhibitors are a primary treatment for erectile dysfunction, effective and well-tolerated in over 70% of cases. There are currently seven PDE5 inhibitors on the market (sildenafil, tadalafil, vardenafil, avanafil, lodenafil, meronafil, and udenafil). Of these, sildenafil, vardenafil, tadalafil, and avanafil are approved by the U.S. Food and Drug Administration (FDA) for the treatment of erectile dysfunction in men, and there is no evidence of a difference in their efficacy.

[0004] PDE5 inhibitors have vasodilatory properties and exert systemic hemodynamic effects; their vascular effects must be considered when used in combination with other cardiovascular drugs. Extra caution is needed when used in combination with alpha-blockers, and PDE5 inhibitors should be contraindicated during nitrate (e.g., nitroglycerin or isosorbide dinitrate) treatment. The combination of these two drugs with PDE5 inhibitors can cause persistent vasodilation, which is extremely dangerous. However, in a rat model of nitrate tolerance, increased PDE5A expression in blood vessels was observed, and inhibition of PDE by zaprinast and vinpocetine, respectively, effectively reversed this tolerance, indicating that PDE upregulation is related to nitrate tolerance. The potential application of PDE5 inhibitors in limiting nitrate tolerance requires further evaluation in clinical trials. Sildenafil should not be used in patients with severe cardiovascular disease, such as angina or severe heart failure, and is contraindicated in patients with hypotension (blood pressure below 90 / 50 mmHg), severe liver damage, retinitis pigmentosa, or a history of stroke or myocardial infarction.

[0005] Therefore, given the existing side effects of PDE5 inhibitors, developing new PDE5 inhibitors with fewer toxic side effects is an important direction for new drug research. Summary of the Invention

[0006] This invention provides a specific PDE5 inhibitory peptide PC-5, the amino acid sequence of which is shown in SEQ ID NO: 1.

[0007] The active peptides described herein can be effectively used to treat male erectile dysfunction.

[0008] The active peptides described in this invention can be further modified or have amino acid substitutions performed, but the activity of the active peptides is still maintained.

[0009] Regarding amino acid sequences, those skilled in the art will recognize that individual substitutions, deletions, or additions of a single amino acid or a small number of amino acids in the encoded sequence of a polypeptide sequence are considered "conserved modification variants," wherein the change would result in the deletion, addition, or substitution of an amino acid by a chemically similar amino acid. Those skilled in the art are familiar with providing conserved representatives of functionally similar amino acids. These conserved modification variants are, in addition to being polymorphic variants (and not excluded from being), interspecific homologs and alleles of the present invention.

[0010] Those skilled in the art are aware of providing conserved substitutes for functionally similar amino acids. The following eight groups each contain amino acids that are conserved substitutes for each other: 1) Alanine (A), glycine (G); 2) Aspartic acid (D), glutamic acid (E); 3) Asparagine (N), glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), threonine (T); and 8) Cysteine ​​(C), Methionine (M).

[0011] The PC-5 peptide of the present invention can be directly administered to mammalian individuals. Administration can be performed via any route commonly used to introduce the PC-5 peptide into an individual. PC-5 peptide compositions according to embodiments of the invention comprise PC-5 peptide compositions suitable for oral, rectal, topical, inhalation (including (but not limited to) via aerosol), buccal (including (but not limited to) sublingual), vaginal, parenteral (including (but not limited to) subcutaneous, intramuscular, intradermal, intra-articular, intrapleural, intraperitoneal, intracerebral, intra-arterial, or intravenous) administration, topical (i.e., skin and mucous membrane surfaces, including tracheal surfaces), and transdermal administration, but the most suitable route in any given case will depend on the nature and severity of the condition being treated. Administration can be local or systemic. Formulations of the compounds can be presented in single-dose or multi-dose sealed containers (e.g., ampoules and vials). The PC-5 peptide of the present invention can be prepared as a mixture of a single-dose injectable form (including (but not limited to) solutions, suspensions, or emulsions) and a pharmaceutically acceptable carrier. The PC-5 peptide of the present invention can also be administered via continuous infusion (using (including but not limited to) micropumps, such as osmotic pumps), single bolus injection, or slow-release reservoir formulations.

[0012] Furthermore, the present invention provides a pharmaceutical composition for treating male erectile dysfunction, comprising a specific PDE5 inhibitory active peptide PC-5, the amino acid sequence of which is shown in SEQ ID NO: 1.

[0013] Specifically, the pharmaceutical compositions and formulations of the present invention may contain pharmaceutically acceptable carriers, excipients, or stabilizers. A pharmaceutically acceptable carrier is determined in part by the specific composition to be administered and the specific method of administering the composition. Therefore, a variety of suitable formulations of the pharmaceutical compositions of the present invention exist (including optional pharmaceutically acceptable carriers, excipients, or stabilizers).

[0014] A pharmaceutically acceptable carrier must be "acceptable" in the sense that it is compatible with other components in the composition and harmless to its recipient. The pharmaceutically acceptable carriers used herein are selected from a variety of organic or inorganic substances that can be used as materials in pharmaceutical formulations and can be incorporated as analgesics, buffers, binders, disintegrants, diluents, emulsifiers, excipients, thickeners, glidants, solubilizers, stabilizers, suspending agents, tonicity agents, mediators, and thickeners. If necessary, pharmaceutical additives such as antioxidants, flavoring agents, coloring agents, flavoring agents, preservatives, and sweeteners may also be added. Examples of acceptable pharmaceutical carriers include carboxymethyl cellulose, microcrystalline cellulose, glycerin, gum arabic, lactose, magnesium stearate, methylcellulose, powders, saline solutions, sodium alginate, sucrose, starch, talc, and water.

[0015] Suitable carriers include (but are not limited to): buffers containing succinate, phosphate, borate, HEPES, citrate, histidine, imidazole, acetate, bicarbonate, and other organic acids; antioxidants, including (but not limited to) ascorbic acid; low molecular weight peptides, including (but not limited to) peptides with fewer than about 10 residues; proteins, including (but not limited to) serum albumin, gelatin, or immunoglobulins; hydrophilic polymers, including (but not limited to) polyvinylpyrrolidone; amino acids, including (but not limited to) glycine, glutamine, asparagine, arginine, histidine or histidine derivatives, methionine, glutamic acid, or lysine; monosaccharides, disaccharides, and other carbohydrates, including (but not limited to) trehalose, sucrose, glucose, mannose, or dextrin; and chelating agents, including (but not limited to) EDTA and disodium ethylenediaminetetraacetate. Disodium; divalent metal ions, including (but not limited to) zinc, cobalt, or copper; sugar alcohols, including (but not limited to) mannitol or sorbitol; salt-forming counterions, including (but not limited to) sodium and sodium chloride; and / or nonionic surfactants, including (but not limited to) Tween™ (including (but not limited to) Tween80 (polysorbate 80) and Tween20 (polysorbate 20)), Pluronics™ and other pluronic acids (including (but not limited to) pluronic acid F68 (poloxamer 188)) or PEG. Suitable surfactants include, for example, (but not limited to) polyethers based on poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (i.e., (PEO-PPO-PEO)) or poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (i.e., (PPO-PEO-PPO)) or combinations thereof. PEO-PPO-PEO and PPO-PEO-PPO are commercially available under the trade names Pluronics™, R-Pluronics™, Tetronics™, and R-Tetronics™ (BASF Wyandotte Corp., Wyandotte, Mich.) and are further described in U.S. Patent No. 4,820,352, which is incorporated herein by reference in its entirety. Other ethylene / polypropylene block polymers may be suitable surfactants. Surfactants or combinations of surfactants may be used to stabilize polyethylene glycol-modified PC-5 peptides against one or more stresses (including, but not limited to, stresses generated by stirring). Some of the above substances may be referred to as “bulking agents.” Some may also be referred to as “tension modifiers.”To achieve product stability and antimicrobial efficiency, antimicrobial preservatives may also be used; suitable preservatives include (but are not limited to) benzyl alcohol, bezalkonium chloride, m-cresol, methylparaben / propylparaben, cresol and phenol or combinations thereof.

[0016] Additionally, the polypeptides of the present invention can be administered to human or animal subjects using known procedures, including but not limited to oral administration, parenteral administration, and transdermal administration. Preferably, the polypeptides are administered via suprafascial, intracapsular, intracranial, intradermal, intrathecal, intramuscular, intraorbital, intraperitoneal, intravenous, parenchymatous, subcutaneous, or sublingual injection, or via catheter administration parenterally. In one embodiment, the active agent is delivered to the subject via targeted delivery to cardiomyocytes through a catheter inserted into the subject's heart.

[0017] For oral administration, the polypeptide formulation of the present invention can be formulated into capsules, tablets, powders, granules, or suspensions. The formulation may contain common additives such as lactose, mannitol, corn starch, or potato starch. The formulation can also be prepared using components such as binders, such as microcrystalline cellulose or cellulose derivatives; gum arabic, corn starch, or gelatin. Additionally, disintegrants such as corn starch, potato starch, or sodium carboxymethyl cellulose can be used. Calcium dibasic phosphate or sodium glycolate starch can also be used. Finally, lubricants such as talc or magnesium stearate can be used.

[0018] Various embodiments of the present invention are anticipated to have valuable applications as components of pharmaceutical preparations for treating a variety of conditions generally defined as pathologies. Therefore, embodiments of the present invention also include pharmaceutical compositions comprising one or more compounds of the present invention and a pharmaceutically acceptable carrier. Preferably, these compositions are in unit dosage forms, such as tablets, pills, capsules, powders, granules, sterile parenteral solutions or suspensions, metered aerosols or liquid sprays, drops, ampoules, auto-injector devices, or suppositories; for oral, parenteral, intranasal, sublingual, or rectal administration, or for administration by inhalation or blowing. To prepare solid compositions such as tablets, the main active ingredient is mixed with a pharmaceutical carrier (e.g., conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate, or gum) and other pharmaceutical diluents (e.g., water) to form a solid preformed composition containing a homogeneous mixture of compounds of the present invention or pharmaceutically acceptable salts thereof. When these preformed compositions are referred to as homogeneous, it means that the active ingredient is uniformly dispersed throughout the composition, allowing it to be easily subdivided into equally effective unit dosage forms, such as tablets, pills, and capsules. The solid preformed composition is then subdivided into unit dosage forms of the type described above, containing from 0.1 to about 500 mg of the active ingredient of the present invention. Typical unit dosage forms contain 1 to 100 mg, for example 1, 2, 5, 10, 25, 50, 100 mg, or 1000 mg to a maximum of 2500 mg of the active ingredient. The novel compositions can be coated or otherwise compounded into tablets or pills to provide dosage forms with the advantage of prolonged action. For example, tablets or pills may contain an inner dose component and an outer dose component, the latter being in the form of an encapsulation of the former. These two components can be separated by an enteric coating layer, which resists disintegration in the stomach and allows the inner component to enter the duodenum intact or delay release. A variety of materials can be used for such enteric coatings or coatings, including a variety of polymeric acids and mixtures of polymeric acids with materials such as shellac, acetyl alcohol, and cellulose acetate. The composition can be contained in vials, sponges, syringes, tubes or other suitable containers.

[0019] This drug is used to cure, alleviate or prevent erectile dysfunction (MED), impotence, female sexual dysfunction (FSD), clitoral dysfunction, female hypoactive sexual desire disorder, female sexual arousal disorder, female sexual pain, female orgasmic dysfunction (FSOD), sexual dysfunction caused by spinal cord injury, and sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs).

[0020] This document describes PDE5 inhibitor peptides; however, the compositions and methods are not limited to the use of PDE5 inhibitors. In some non-limiting embodiments, other drugs may be further added, including, for example, melanocortin receptor, oxytocin and oxytocin receptor agonists, neuropeptide Y (NPY) inhibitors, dopamine receptor agonists (e.g., apomorphine), melanocortin receptor agonists, intracavitary therapy, growth hormone-releasing peptide receptor agonists, serotonin receptor agonists, alpha-adrenergic receptor antagonists, topical therapy, guanylate cyclase activators, and rho kinase antagonists.

[0021] Beneficial effects This invention provides the application of bioactive peptides in the treatment of male erectile dysfunction. Specifically, it provides a PDE-5 inhibitory bioactive peptide, PC-5, which effectively inhibits the activity of PDE-5 in human primary cavernous body smooth muscle cells, increasing the intracellular cGMP concentration. Mouse experiments have demonstrated that the peptide can significantly improve sexual function in mice. Furthermore, the peptide can overcome common side effects of common erectile dysfunction medications, including headache, hot flashes, stomach upset, muscle pain, back pain, and nausea. The peptide can also be used in combination with other drugs for ED treatment, showing broad application prospects. Attached Figure Description

[0022] Figure 1 The effect of the peptide of this invention on the expression of PDE5 protein in cells is shown in the figure; the results are based on the relative expression level of the blank group.

[0023] Figure 2 The effect of the peptides of this invention on PDE5 activity in the penis of mice in various experimental groups is shown in the figure. Detailed Implementation Those skilled in the art can refer to the content of this document and appropriately improve the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to implement and apply the technology of this invention. Unless otherwise specified, the methods, equipment, and materials in the following embodiments are all conventional methods, equipment, and materials in the art and are commercially available.

[0024] Example 1: Screening and preparation of PDE5 inhibitory active peptides Crystal structure data of PDE5 from humans, mice, and rats were downloaded from the PDB (Protein Data Bank) database. The common active site of PDE5 in the three species was predicted using Discovery Studio software, and the coordinates and amino acid types of the active site were determined. Virtual screening was performed using the Maybridge database, selecting 11 candidate inhibitory peptides. Molecular docking of the candidate inhibitory peptides was performed using Autodock Vina software to predict their binding positions and energies with PDE5. The candidate inhibitory peptides were evaluated and screened by calculating parameters such as intermolecular affinity, energy, and activity. Finally, the most active PDE5 inhibitory peptide, PC-5, was identified, and its amino acid sequence is shown in SEQ ID NO: 1. The peptide was artificially synthesized by Nanjing GenScript Biotech Co., Ltd. The peptide was water-soluble and its concentration was adjusted to 5 mg / mL for later use.

[0025] Example 2 Cellular Experiments with PDE5 Inhibitory Peptide PC-5 Human primary corpus cavernosum smooth muscle cells (catalog number: HUM-YJ-f038, Shanghai Yanjin Biotechnology Co., Ltd.) were seeded into DMEM medium containing 1% fetal bovine serum and cultured statically at 37°C. The cells were then passaged into 24-well plates at a cell density of 1.5 × 10⁶ cells / well. 4 The wells of the plate were divided into 6 groups: PDE5 inhibitory peptide PC-5 at final concentrations of 10 μg / mL (A), 50 μg / mL (B), 100 μg / mL (C), and 200 μg / mL (D). The blank group received no peptide. The positive control group received 50 μg / mL sildenafil tablets. All groups were cultured for 4 h. Cells were digested with trypsin, resuspended in PBS, centrifuged to remove PBS, and then resuspended in 100 μl of PBS. 100 μl of PBS containing 20% ​​trichloroacetic acid (V / V) was added. The cells were extracted three times with ether at 70℃ for 5 min, after which the ether evaporated automatically. After sample purification, the cGMP assay kit was followed, and the maximum binding number (B0) and sample reading (B) were measured. The results are expressed as B / B0 (%). The results are shown in Table 1.

[0026] Table 1. cGMP content results for each group As shown in Table 1, both the peptide and the positive control significantly improved the B / B ratio, and the intracellular cGMP content was significantly increased compared to the blank group. This indicates that the PDE5 inhibitory active peptide PC-5 of the present invention can inhibit the expression of PDE5 in corpus cavernosum smooth muscle cells, thereby increasing the intracellular cGMP concentration in smooth muscle cells.

[0027] Total protein was extracted from cells in each group, and protein concentration was measured. Protein samples (50 μg) were separated using 100 g / L SDS-PAGE, and transferred to a PVDF membrane after constant current at 250 mA for 100 min. The membrane was blocked with skim milk at room temperature for 1 h, and incubated overnight at 4 ℃ with primary antibody (1:1000) PDE5. After incubation with secondary antibody (1:3000) horseradish peroxidase-labeled goat anti-rabbit IgG at room temperature for 2 h, the immunoblot was detected using an ECL chemiluminescence system. Band intensity was quantified using Quantity One software. The relative expression level of PDE5 in each group was expressed as 100% with the blank group as the control group. The results are shown below. Figure 1 As shown.

[0028] from Figure 1 It can be seen that with the increase of the concentration of the PDE5 inhibitory peptide PC-5, the expression level of PDE5 protein gradually decreased. At 200 μg / mL, the relative expression level of PDE5 protein decreased to (10.9±1.8), and from... Figure 1 It can also be seen that, at the same concentration, the polypeptide of the present invention has a stronger inhibitory effect on PDE5 protein expression than the positive control group.

[0029] Example 3: Mouse experiment with PDE5 inhibitory active peptide PC-5 SPF-grade ICR mice [(25±2) g], half male and half female, were purchased from Hunan Slack Jingda Experimental Animal Co., Ltd. The animals were housed in a sterile environment at a temperature of 22–26 °C and a humidity of 50%–60%, with alternating light and dark conditions for 12 hours, and free access to food and water.

[0030] After 7 days of acclimatization, male ICR mice were randomly divided into 5 groups, with 10 mice in each group: a control group (equal volume of distilled water); a model group (paroxetine, 14 mg / kg); and a model group (paroxetine, 14 mg / kg). -1 PRX); Positive group: (14 mg·kg) -1 PRX + 5mg·kg -1 Sildenafil); Low-dose group of PDE5 inhibitory active peptide PC-5: (14 mg·kg) -1 PRX + 5mg·kg -1 (peptide); High-dose group of PDE5 inhibitory active peptide PC-5: (14 mg·kg -1 PRX + 10 mg / kg -1 (Polypeptide); mice in all experimental groups were administered oral gavage for 28 consecutive days.

[0031] Mating experiments were conducted 1 hour after the last administration of the drug.

[0032] Forty-eight hours before mating, female mice were intramuscularly injected with 0.2 mg / mouse of estradiol benzoate solution, and four hours prior, they were injected with 1 mg / kg of progesterone solution to induce estrus. The experiment was recorded using a high-definition camera, starting from when the female mice were placed in the cages. Mating behavior parameters for the first 30 minutes were observed and recorded, including mounting latency (ML), mounting frequency (MF), penetration latency (IL), penetration frequency (IF), ejaculation latency (EL), and post-ejaculation interval (PEL). The results are shown in Table 2.

[0033] Table 2. Effects of peptides on sexual function in mice. As shown in Table 2, compared with the blank group, the peptide significantly prolonged ML, IL, EL, and PEL in mice, demonstrating a good effect on improving sexual function. At the same concentration, the peptide exhibited better therapeutic effects than the positive control group, indicating broad application prospects.

[0034] The penises of mice in each group were removed, and penile tissue homogenates were prepared according to the instructions of the kit (Mouse Phosphodiesterase 5 (PDE5) ELISA Kit purchased from Dixintai Detection Technology (Beijing) Co., Ltd.), and the PDE5 activity in the homogenates was measured. The results are as follows: Figure 2 As shown.

[0035] Depend on Figure 2 It was found that, compared with the blank group, the model group showed significantly increased PDE5 activity due to erectile dysfunction in male mice caused by PRX administration (P<0.01). Compared with the model group, the positive control group, as well as the low-dose and high-dose peptide groups, all significantly reduced PDE5 activity in mouse penile tissue (P<0.01, compared with the model group). The reduction was particularly pronounced in the high-dose peptide group.

[0036] In addition, the heart, spleen, liver, kidneys and lungs of mice in each group were tested and no obvious drug toxicity was found. The visceral coefficients of the low-dose peptide group and the high-dose peptide group of the present invention were not significantly different compared with the blank group (P>0.05), which also shows that the peptides of the present invention have good safety.

[0037] Finally, the left and right epididymis of each group of mice were minced in EP tubes containing physiological saline, shaken well, and incubated in a 37°C water bath for 15 minutes. A drop of the diluted solution was taken and smeared onto a slide. 300 sperm cells were observed, and the number of motile sperm cells was counted to calculate sperm viability. Sperm viability = (number of motile sperm / 300) × 100%. The results are shown in Table 3.

[0038] Table 3. Sperm viability (%) in each group As shown in Table 3, the sperm motility of mice in the model group was significantly lower than that in the control group (P<0.01); while compared with the model group, both the positive control group and the high- and low-dose peptide groups effectively improved sperm motility (P<0.01). These results indicate that peptide intervention significantly improves the sexual function of male mice, making it an effective treatment for erectile dysfunction with broad application prospects.

[0039] It should be understood that the examples and embodiments described herein are for illustrative purposes only and are intended to indicate to those skilled in the art various modifications and variations that may be made thereto, and such modifications and variations are included within the spirit and scope of this application and the appended claims. All publications, patents, patent applications and / or other documents cited in this application are incorporated herein by reference in their entirety for all purposes, as if each publication, patent, patent application and / or other document were individually incorporated herein by reference for all purposes.

Claims

1. A specific PDE5 inhibitory peptide PC-5, characterized in that... The amino acid sequence is shown in SEQ ID NO:

1.

2. Use of the specific PDE5 inhibitory active peptide PC-5 as described in claim 1 in the preparation of a pharmaceutical composition for treating erectile dysfunction in men.

3. Use according to claim 2, characterized in that The pharmaceutical composition contains a pharmaceutically acceptable carrier.

4. The use as described in claim 2, wherein the pharmaceutical composition is in the form of a capsule, tablet, granule or suspension.

5. Use according to any one of claims 2 to 4, characterized in that The active peptide PC-5 is used in combination with a second therapeutic agent, which is an antioxidant.

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