Formulation and manufacturing process of penile erecting gel

Abstract

The formulation of penile erecting gel comprises biosynthesized silver nanoparticles derived from Kaempferia parviflora extract containing 5,7-Dimethoxyflavone, in combination with sodium hyaluronate, isoprene glycol, phenoxyethanol, glycerin, propylene glycol, and ethylhexylglycerin. The manufacturing process involves blending the specified components, stirring to form a homogeneous gel, adding natural colorants and fragrances, and packaging in single-use plastic vials or aluminum foil sachets. This formulation represents an innovative application of nanotechnology in combination with Thai herbal medicine, enhancing localized vasodilation specifically at the penile region while minimizing systemic side effects such as headaches, nasal congestion, facial flushing, and blue-tinted vision associated with oral phosphodiesterase type 5 inhibitors (PDE5 inhibitors) like sildenafil (Viagra) or tadalafil (Cialis). Additionally, the gel exhibits antimicrobial and antioxidant properties.

Description

[0001] FORMULATION AND MANUFACTURING PROCESS OF PENILE ERECTING GEL

[0002] Field of the Invention

[0003] The present invention relates to the field of science and technology, specifically to the formulation and manufacturing process of penile erecting gel.

[0004] Summary of the Invention

[0005] The formulation and manufacturing process of penile erecting gel comprises biosynthesized silver nanoparticles derived from Kaempferia parviflora extract and 5,7- Dimethoxyflavone, in combination with sodium hyaluronate, isoprene glycol, phenoxyethanol, glycerin, propylene glycol, and ethylhexylglycerin. The method of preparation involves blending the specified components in precise proportions, stirring for 30 minutes to form a homogeneous gel, adding natural colorants and fragrance, and packaging the final product in single-use plastic containers or aluminum foil sachets. This gel formulation represents an innovation that integrates nanotechnology with traditional Thai herbal medicine to enhance localized vasodilation specifically in the penile and adjacent areas, thereby reducing systemic side effects commonly associated with oral phosphodiesterase type 5 (PDE-5) inhibitors such as Viagra or Cialis. These undesirable effects include headaches, nasal congestion, facial flushing, and transient, blue-tinted vision caused by systemic vasodilation.

[0006] The primary objective of this invention is to develop an innovative herbal-based erectile enhancement gel utilizing nanotechnology to promote localized blood vessel expansion while minimizing systemic side effects, such as headaches, nasal congestion, facial flushing, and transient, blue-tinted vision caused by systemic vasodilation resulting in the consumption of Viagra or Cialis. The gel is packaged in pre-measured single-use containers or aluminum foil sachets and provides noticeable effects within 6-10 minutes after application.

[0007] Background of the Invention

[0008] Erectile dysfunction (ED) is medically defined as the inability to achieve or maintain an erection sufficient for sexual intercourse. It is a condition that becomes more prevalent with age and can significantly impact quality of life and relationships. ED results from multiple factors, including hormonal imbalances (low testosterone), diabetes, hypertension, hyperlipidemia, alcohol consumption, smoking (including e-cigarettes), lack of exercise, insufficient rest, previous pelvic or prostate surgeries, urinary tract surgeries, depression, and the use of certain medications that affect the central nervous system. These include sedatives, antihypertensive drugs, antidepressants, and alcohol consumption, as well as psychological and emotional factors.

[0009] The World Health Organization (WHO) recommends a stepwise approach to treating ED, starting with pharmacological treatment. Medications can be administered orally, through injections, or as suppositories. In addition, shockwave therapy has emerged as an alternative treatment for ED rehabilitation. After a comprehensive health assessment, physicians often advise patients to discontinue medications that affect erectile function, maintain a healthy weight, exercise regularly, quit smoking and alcohol consumption, get adequate rest, and manage stress. The primary treatment remains oral medications, which function by dilating blood vessels to improve blood flow to the penile region, thereby enhancing erection quality. However, oral medications have limitations as they primarily treat the symptoms rather than the underlying cause. Erections achieved with medication may feel less natural, require continuous drug use, and depend on vascular health for optimal effectiveness. To address these limitations, the formulation of penile erecting gel has been developed as a novel nano-technology innovation utilizing Thai herbal extracts. This formulation aims to restore natural erectile function and enhance intimate relationships.

[0010] Currently, various ED treatment products are available on the market, primarily targeting vasodilation and increased blood circulation. These include oral medications, injectable therapies, and shockwave devices. The present invention seeks to develop a penile erecting gel, formulated using biologically synthesized silver nanoparticles derived from Kaempferia parviflora as the key active ingredient in the erectile mechanism.

[0011] Studies have shown that Kaempferia parviflora extract (Kaempferia parviflora) enhances vascular relaxation in animal models by modulating the nitric oxide (NO) / (cGMP) pathway and activating potassium channels. Additionally, it inhibits calcium influx via voltage-dependent potassium channels, contributing to blood vessel relaxation. Research indicates that polymethoxyflavones, particularly 5,7-dimethoxyflavone (DMF) with a molecular weight of 282.29 g / mol, play a crucial role in penile vascular relaxation. Clinical trials have demonstrated that a daily oral dose of 90 mg of Kaempferia parviflora extract improves sexual arousal response, penile size, erection quality, ejaculation time, and overall sexual satisfaction. Notably, the effects persist for up to two months with continuous supplementation. The study also found that 50% of participants reported improved erectile function and sexual performance, with statistically significant differences compared to the placebo group.

[0012] The research team has developed silver nanoparticles derived from Kaempferia parviflora, measuring 20-40 nanometers, to enhance cellular absorption. The formulation incorporates bioactive compounds, including Kaempferia parviflora extract (KPE) and 5,7-dimethoxyflavone (DMF), which penetrate endothelial cells to stimulate nitric oxide production, leading to rapid vasodilation and smooth muscle relaxation.

[0013] Brief Description of the Drawing Figure 1 : The Role of Endothelial Cells and Smooth Muscle Cells in Vasodilation

[0014] Detailed Description of the Invention

[0015] Mechanism of Action of Kaempferia parviflora Extract in Erectile Function Enhancement

[0016] The mechanism of penile erection is primarily driven by vascular dilation, which increases blood flow to the penile tissue. The efficacy of Kaempferia parviflora extract (KPE) and its active compound, 5,7-Dimethoxyflavone (DMF), is compared to phosphodiesterase type 5 (PDE5) inhibitors such as Sildenafil and Tadalafil in Table 1. There are two primary mechanisms by which vascular dilation occurs, and both KPE and DMF exhibit their effects through both pathways, as illustrated in Figure 1 :

[0017] 1. Endothelium-Dependent Pathway

[0018] This pathway involves the activation of endothelial cells that line blood vessels. When blood pressure increases up to fourfold and blood flow rises by up to 100 times, intracellular calcium levels increase, triggering the enzyme endothelial nitric oxide synthase (eNOS) to produce nitric oxide (NO). Additionally, this process stimulates the enzyme cyclooxygenase (COX), leading to the production of prostaglandin E (PGE), a potent vasodilator. Another key factor, endothelium-derived hyperpolarizing factor (EDHF), enhances vascular relaxation by facilitating potassium ion efflux through specialized channels in smooth muscle cells.

[0019] 2. Endothelium-Independent Pathway

[0020] Kaempferia parviflora extract also exerts a direct effect on smooth muscle cells, independent of endothelial function. EDHF activates potassium channels, causing potassium ions to exit the cells. This results in hyperpolarization, reducing intracellular potassium concentration and rapidly relaxing the smooth muscle surrounding blood vessels. Additionally, PGI2, produced by endothelial cells, inhibits adenylate cyclase, which normally converts adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). This inhibition activates protein kinase A (PKA), leading to a rapid reduction in intracellular calcium ions, further promoting smooth muscle relaxation. Furthermore, during sexual arousal, non-adrenergic, non-cholinergic (NANC) nerve activity triggers NO production, which activates guanylate cyclase to convert guanylate triphosphate (GTP) into cyclic guanosine monophosphate (cGMP). This pathway induces smooth muscle relaxation via protein kinase G (PKG) activation. Overall, the cGMP -mediated pathway plays a more dominant role in penile smooth muscle relaxation than the cAMP pathway.

[0021] Table 1: Comparison of Vasodilation Mechanisms Between Kaempferia parviflora Extract (KPE and 5,7-DMF) and PDE5 Inhibitors (Sildenafil, Tadalafil)

[0022] Note: Kaempferia parviflora extract (KPE) and 5, 7 -Dimethoxyflavone (DMF)

[0023] Reference:

[0024] 1. Patcharin Tep-areenan, Pattara Sawasdee, Michael Randall. Possible Mechanisms of Vasorelaxation for 5,7-Dimethoxyflavone from Kaempferia parvifl ora in the Rat Aorta. Phytother. Res. 24: 1520-1525 (2010) Published online 1 June 2010 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002 / ptr.3164.

[0025] 2. Parchorin Tep-areenan, Komkanok Ingkaninan, Michael Randall. Possible Mechanisms of Kaempferia parviflora extract (KPE)- induced vasorelaxation in the rat aorta. Asian Biomedicine Vol. 4 No. 1 February 2010; 103-111.

[0026] In conclusion, the combination of Kaempferia parviflora extracts (KPE and 5,7-DMF) promotes vasodilation, leading to penile erection through both endothelium-dependent and endothelium-independent mechanisms. Ultimately, these processes contribute to smooth muscle relaxation via the cGMP and cAMP pathways. The biologically synthesized silver nanoparticles, coated with Kaempferia parviflora extract, are 20-40 nanometers in size and formulated into a penile erecting gel. These silver nanoparticles penetrate the skin and rapidly reach the blood vessels within the corpus cavernosum, triggering a rapid erectile response.

[0027] Scientific evidence highlights the extract’s ability to stimulate nitric oxide (NO) production, which relaxes smooth muscle cells in the penile blood vessels within the corpus cavernosum. This vasodilation, contained within the tunica albuginea, compresses the venous outflow, thereby facilitating a sustained erection.

[0028] Additionally, female sexual dysfunction (FSD), often associated with menopause, results in decreased levels of sex hormones. Reduced estrogen leads to vaginal dryness, while decreased androgen levels lower sexual desire. The penile erecting gel according to the present invention is designed for both male and female use, containing silver nanoparticles infused with Kaempferia parviflora extract at a pH level of 6-7, ensuring stability and long-term efficacy. Furthermore, the antimicrobial properties of silver nanoparticles enable broad-spectrum bacterial inhibition, including antibiotic-resistant and non-resistant strains. Currently, vasodilatory treatments remain the primary approach for addressing erectile dysfunction (ED). This gel works by enhancing blood circulation to the genital area, providing a natural and effective alternative to traditional treatments.

[0029] Clinical Trial Results (Table 2)

[0030] A clinical trial (Table 2) was conducted with 29 male volunteers, each receiving five sachets of gel containing 0.68 g / L of Kaempferia parviflora extract, KPE-AgNP (Kaempferia parviflora-derived silver nanoparticles) at concentrations of 2.5, 5.0, 7.5, and 10.0 mg / L, and 5,7- Dimethoxyflavone (DMF) at 0.5 mg / L. However, only 22 participants completed the study and provided complete data, while five participants withdrew, and two submitted incomplete records. Among the 22 evaluated participants, 13 were healthy, while nine had diabetes and hyperlipidemia. Both groups had similar testosterone levels. The study found that the 10 mg / L KPE-AgNP formulation produced the fastest erection onset, occurring within 6.0 ± 3.6 minutes in the healthy group and 7.7 ± 4.1 minutes in participants with diabetes and hyperlipidemia. In both groups, the erection hardness exceeded level 3, meaning the erection was sufficient for vaginal penetration. For participants using gels with lower KPE-AgNP concentrations (<10 mg / L), only the healthy group achieved penetration-capable erections. In contrast, participants with comorbidities experienced some penile enlargement but were unable to achieve full penetration. Those using the 2.5 mg / L formulation in both groups did not achieve functional erections, with penile hardness reaching only level 2, insufficient for penetration. The clinical trial concluded that a minimum concentration of 10 mg / L KPE-AgNP is necessary for effective erectile function, showing efficacy in both healthy individuals and those with diabetes and hyperlipidemia.

[0031] Table 2: A comparative analysis of the two participant groups, evaluating erectile response following topical application of Kaempferia parviflora-derived silver nanoparticle gel (KPE- AgNP) at different concentrations (2.5, 5.0, 7.5, and 10.0 mg / L). The control group used a gel containing only Kaempferia parviflora extract (KPE) and 5,7-Dimethoxyflavone (DMF).

[0032] *Note: Volunteers with PHS > 3 were able to penetrate (placebo effect).

[0033] Currently, there are several synthetic drugs available on the market for erectile dysfunction treatment, including sildenafil, vardenafil, and tadalafil. However, these medications often cause undesirable side effects such as headaches, facial flushing, nasal congestion, and blue-tinted vision. Additionally, they are highly expensive. In contrast, the topical gel formulation developed in this invention contains a natural herbal extract — Kaempferia parviflora-derived silver nanoparticles (KPE-AgNP) at a concentration of at least 10 mg / L. This herbal -based solution, applied directly to the glans penis, enhances male vitality and erectile function, benefiting both healthy individuals and those with diabetes or hyperlipidemia. The gel boosts sexual desire, improves penile blood circulation, and increases sensitivity to stimulation. Furthermore, it contains sodium hyaluronate, which hydrates the penile skin, giving it a plumper, healthier, and pinker appearance. This topical male enhancement gel offers a natural alternative to synthetic pharmaceutical drugs, reducing dependence on expensive imported medications. It is affordable and accessible to men regardless of financial status.

[0034] The formulation of penile erecting gel according to the present invention comprises the following components:

[0035] Deionized water 85.398 92.91 percent by weight

[0036] Biosynthesized silver nanoparticles 1.9 percent by weight containing KPE and 5,7-DMF

[0037] Sodium hyaluronate 0.01 0.012 percent by weight

[0038] Isoprene glycol 4.12 5.87 percent by weight

[0039] Phenoxyethanol 0.35 0.66 percent by weight

[0040] Glycerin 0.65 1.42 percent by weight

[0041] Propylene glycol 0.45 1.86 percent by weight Ethylhexylglycerin 0.04 - 0.21 percent by weight

[0042] Hydroxyethyl cellulose 1.14 - 2.31 percent by weight

[0043] Glyceryl trinitrate 0.01 - 0.24 percent by weight

[0044] Phentolamine 0.01 - 0.24 percent by weight

[0045] Natural colorants and fragrance 0.18 - 0.36 percent by weight

[0046] The method for manufacturing the penile erecting gel comprises the steps of: a. Preparing an aqueous extract of Kaempferia parviflora containing 5,7- Dimethoxyflavone at a concentration of no less than 150 mg%, by boiling the extract in distilled water at 60°C on a heated magnetic stirrer for 30 minutes; filtering the extract to remove solid residues using Whatman No.1 filter paper; storing the filtered extract at 4°C in a refrigerated system; and analyzing the protein content in the extract by measuring its absorbance at 230 nm using a UV-Vis spectrophotometer. b. Mixing 900 mL of a 10 mM silver nitrate (AgNO3) solution (Sigma-Aldrich, USA) with 100 mL of a reducing agent obtained from Step a.; heating the mixture at 50 - 60°C for 6 - 8 hours; observing the color change from a clear, colorless solution to a reddish-brown solution, indicating the formation of silver nanoparticles; allowing the solution to cool to room temperature; centrifuging the solution to precipitate the silver nanoparticles; washing the precipitate twice with deionized water; analyzing the supernatant from the second wash for nitrate ions by adding 1 mL of a saturated ferric sulfate solution, followed by the gradual addition of concentrated sulfuric acid, resulting in the formation of a brown ring at the interface; dissolving the silver nanoparticle precipitate in aqueous Kaempferia parviflora extract, yielding silver nanoparticles infused with 5,7-Dimethoxyflavone (5,7-DMF) at a concentration of 4,000 - 5,000 ppm, with 5,7-DMF content ranging from 32 - 68 mg%. c. Measuring the absorbance of silver nanoparticles using a UV-Vis spectrophotometer with a resolution of 1 nanometer over a wavelength range of 300 - 800 nm to study nanoparticle formation; analyzing the morphology and size of silver nanoparticles (AgNPs) using Transmission Electron Microscopy (TEM) at an accelerating voltage of 200 kV, with the sample being sonicated for 5 minutes, deposited onto a carbon-coated copper grid, and vacuum-dried before imaging; characterizing the crystalline structure of silver nanoparticles using X-ray diffraction (XRD) at a 29 range of 10 - 60 degrees to determine crystallinity; identifying organic compounds, proteins, and phytochemicals responsible for nanoparticle stabilization using a Fourier Transform Infrared Spectrometer (FTIR), recording spectra in the 400 - 4000 cm1range; evaluating the stability of synthesized silver nanoparticles by measuring absorbance changes and particle size at various time intervals (1, 7, 14, 30, 60, and 120 days) using UV-Vis spectrophotometry and TEM analysis. d. Dissolving Kaempferia parviflora-derived silver nanoparticles (containing KPE and 5,7 DMF-AgNP) at a concentration of 0.15 - 1.9% by weight, sodium hyaluronate at 0.01 - 0.012% by weight, isoprene glycol at 4.12 - 5.87% by weight, phenoxyethanol at 0.35 - 0.66% by weight, glycerin at 0.65 - 1.42% by weight, propylene glycol at 0.45 - 1.86% by weight, ethylhexylglycerin at 0.04 - 0.21% by weight, glyceryl trinitrate at 0.01 - 0.24% by weight, and phentolamine at 0.01 - 0.24% by weight, using a solvent to achieve homogeneity; and homogenizing the mixture by stirring at a speed of SOO- SOO RPM for 5-10 minutes. e. Mixing 1.14 - 2.31% by weight of hydroxy ethyl cellulose in deionized water, allowing it to hydrate and act as a binder, then stirring at 300 - 500 RPM for 30 minutes until fully dissolved into a clear solution, followed by cooling to obtain a slightly viscous, transparent liquid. f. Mixing the solution from Step d. with the solution from Step e., then stirring at 300 - 500 RPM for 20 - 25 minutes until fully homogenized, resulting in a clear, viscous liquid. g. Adding preservatives, colorants, and fragrance (as desired) to the solution from Step f., followed by deionized water to achieve a total composition of 100% by weight; mixing the solution at a speed of 300 - 500 rpm for 5 - 10 minutes until a smooth, transparent gel with a uniform texture and viscosity is formed; adjusting the pH to approximately 6 - 7, measured using universal indicator paper; allowing the gel to stand at room temperature below 40°C. h. Filling the gel into single-use aluminum sachets in quantities of 1.5 - 2.0 mF, ensuring suitability for topical application to the glans penis.

[0047] The penile erecting gel enhances erection firmness, with effects observable within 6 - 10 minutes and lasting temporarily for 30 - 60 minutes. The formulation of the gel contains a carefully balanced composition of Kaempferia parviflora-derived silver nanoparticles, Kaempferia parviflora extract, and 5,7-Dimethoxyflavone, ensuring optimal efficacy. The pH is adjusted to approximately 6 - 7, which enhances the stability of the silver nanoparticles, allowing them to remain active for an extended period. Additionally, the formulation exhibits broad-spectrum antibacterial properties, effectively targeting both antibiotic-resistant and non-resistant bacteria, as demonstrated in Table 3.

[0048] Table 3: Antibacterial Efficacy of Silver Nanoparticles, Kaempferia parviflora Extract

[0049] (KPE), and Kaempferia parviflora-Derived Silver Nanoparticles Against General and

[0050] 5 Antibiotic-Resistant Bacteria in Hospital Settings.

[0051] Note: ND = Not detected

[0052] Best Mode of the Invention

[0053] As described in the Detailed Description of the Invention section.

Claims

Claims1. The formulation of penile erecting gel, comprising:Deionized water 85.398 92.91 percent by weightBiosynthesized silver nanoparticles0.15 1.9 percent by weight containing KPE and 5,7-DMFSodium hyaluronate 0.01 0.012 percent by weightIsoprene glycol 4.12 5.87 percent by weightPhenoxyethanol 0.35 0.66 percent by weightGlycerin 0.65 1.42 percent by weightPropylene glycol 0.45 1.86 percent by weightEthylhexylglycerin 0.04 0.21 percent by weightHydroxyethyl cellulose 1.14 2.31 percent by weightNatural colorants and fragrance 0.18 0.36 percent by weight2. The method for manufacturing the penile erecting gel according to Claim 1, comprising the steps of: a. Synthesizing silver nanoparticles using an aqueous extract of Kaempferia parviflora containing at least 150 mg% of 5 -Dimethoxy flavone as a reducing and stabilizing agent, wherein the extract is prepared by boiling at 60°C for 30 minutes, filtering through Whatman No. 1 filter paper, and storing at 4°C; mixing 900 mL of a 10 mM silver nitrate (AgNO3) solution with 100 mL of the Kaempferia parviflora extract, followed by heating at 50 - 60°C for 6 - 8 hours until the solution develops a reddish- brown color; centrifuging the solution and washing the precipitate twice, followed by nitrate ion analysis in the supernatant; dissolving the obtained precipitate in the Kaempferia parviflora extract, yielding silver nanoparticles containing 5,7- Dimethoxyflavone at a concentration of 0.88 - 1.97 mM; characterizing the nanoparticles using UV-Vis spectrophotometry to measure absorption in the range of 300-800 nm, Transmission Electron Microscopy (TEM) to analyze particle morphology and size after 5 minutes of sonication and vacuum drying, X-ray Diffraction (XRD) to examine crystal structures at 29 = 10-60°, and Fourier Transform Infrared Spectroscopy (FTIR) to analyze protein components and phytochemicals responsible for nanoparticle stabilization in the range of 400-4000 cm evaluating nanoparticle stability by monitoring absorption changes and particle size variations at 1, 7, 14, 30, 60, and 120 days.b. Incorporating Kaempferia parviflora-derived silver nanoparticles containing 5,7- Dimethoxyflavone at concentrations of 0.88 - 1.97 mM in an amount of 0.15 - 1.9% by weight, sodium hyaluronate at 0.01 - 0.012% by weight, isoprene glycol at 4.12 - 5.87% by weight, phenoxyethanol at 0.35 - 0.66% by weight, glycerin at 0.65 - 1.42% by weight, propylene glycol at 0.45 - 1.86% by weight, ethylhexylglycerin at 0.04 - 0.21% by weight, hydroxyethylcellulose at 1.14 - 2.31% by weight, and natural colorants and fragrances at 0.18 - 0.36% by weight, followed by the addition of deionized water to achieve a total composition of 100% by weight; thoroughly mixing the ingredients and stirring for 30 minutes to obtain a smooth, transparent gel with uniform viscosity; adjusting the pH to approximately 6 - 7, as measured using universal indicator paper; allowing the gel to stand at room temperature below 40°C before packaging into aluminum sachets.

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