Aphrodisiac composition and management of male sexual dysfunction

Abstract

The present invention discloses a composition for the therapeutic management of male sexual dysfunction and related disorders. Specifically, the composition contains 60-65 w / w% Withania somnifera extract, 12-18 w / w% Mucana pruriens extract, 5-10 w / w% Coleus forskolii extract, 12-18 w / w% Kaempferia parviflora extract, and 0.1-2 w / w% Piper nigrum extract for use as an aphrodisiac.

Description

Technical Field

[0001] Cross - reference to related applications This application claims priority from Indian Patent Application No. 201941006993, filed on February 22, 2019, under the Paris Convention. Field of the Invention The present invention relates to compositions for the treatment management of male sexual dysfunction and related disorders. Specifically, the present invention relates to compositions comprising plant extracts and phytochemicals for managing disorders associated with male sexual dysfunction.

Background Art

[0002] Male sexual arousal is caused by a complex biochemical pathway, physical events, and psychological events involving the nervous system and vascular system, including the brain, neurotransmitters, second messengers, smooth muscle, blood vessels, etc. Sexual dysfunction occurs when the pathways involved in any of the above are disrupted. Common types of male sexual dysfunction include erectile dysfunction, premature ejaculation, retarded ejaculation or inhibited ejaculation, and decreased libido. A combination of physical and physiological problems can cause sexual dysfunction, especially erectile dysfunction, in males. The brain plays an important role in initiating a series of physical events that cause an erection and starting to feel sexual arousal. Depression, anxiety or other mental health conditions, stress or relationship problems due to stress, and lack of communication can cause or exacerbate erectile dysfunction.

[0003] According to the latest explanation, penile erection is a complex process involving psychogenic, hormonal, and neurovascular non-adrenergic non-cholinergic mechanisms. Nitric oxide produced by the corpus cavernosum is the main vasoactive, non-cholinergic, non-adrenergic neurotransmitter and chemical mediator of erectile function. Nitric oxide stimulates guanylate cyclase, an enzyme that converts GTP to 3',5'-cyclic guanosine monophosphate (cGMP), which relaxes arterial smooth muscle and increases blood flow to the penis. The veins that carry blood away from the penis contract, resulting in the trapping of pressurized blood in the corpus cavernosum, thereby causing an erection. Furthermore, cGMP levels play a major role in maintaining an erection for an extended period. Ideally, cGMP is converted to 5'GMP by phosphodiesterase enzymes, thereby suppressing an erection. Inhibition of phosphodiesterase enzymes can sustain penile erections that provide sexual satisfaction (please provide references).

[0004] Therefore, for the treatment of penile dysfunction and the therapeutic management of related male sexual dysfunctions, it is necessary to target all stages of the mechanism of increasing nitric oxide levels to increase penile blood flow, activating the enzyme guanylate cyclase to increase the levels of cyclic monophosphate (cGMP), and increasing the levels of cGP-specific protein kinase to increase smooth muscle relaxation. The latest chemical compositions contain one or more agents that act via various pathways in the treatment of male sexual dysfunctions. A brief mention of the prior art is made below. International Application WO2018220232 describes compositions containing botulinum toxin, mainly onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA; PDE5 inhibitors, mainly sildenafil citrate, udenafil, avanafil, milodenafil, sildenafil, tadalafil, and other derivatives, for use mainly in the treatment of erectile function, either simultaneously, consecutively, or separately.

[0005] In U.S. Patent Application No. 15 / 434,226, entitled "Composition and method for treatment of erectile dysfunction", the use of one chemically active anti-erectile dysfunction drug (AED), such as vardenafil, avanafil, and pharmaceutically acceptable salts thereof, in combination with cannabis and its extracts is disclosed. U.S. Patent No. 7,147,874 discloses that a pharmaceutical composition is provided for the prevention and treatment of premature ejaculation and / or hypersensitivity to sexual stimulation. The composition includes a purified sumsoo extract and a purified ginseng extract containing saponin as the main component, and does not include other herbal essential oil components.

[0006] U.S. Patent Application Publication No. 2006 / 0269623 teaches a herbal composition and a treatment method for preventing or treating erectile dysfunction disorder and improving its symptoms, and as a preventive means for erectile dysfunction. The method includes the step of administering a therapeutically effective composition containing the following herbs and other ingredients: Herba Cynomorii, Rhizhomnas atractylodis macrocephalae, Radix rehmannia glutinosea longui, Herba epimedii, Fructus lycii, Fructus schisandrae chinensis, Radix poloygoni multiflor, Cortex cinnamonia cassiae, Fructus amoni, and Radix ginseng. Kotta et al. (Kotta et al., Exploring scientifically proven herbal aphrodisiacs, Pharmacogn Rev. 2013 Jan-Jun; 7(13): 1-10) have reviewed various herbal aphrodisiacs used in the Ayurvedic system of medicine. Various other devices, such as vacuum devices, penile implants, etc. are also available, but they are useful only for patients with significantly impaired function. It has been recognized that bruising, skin damage, and penile pain may occur when using these devices.

[0007] Existing treatments for male sexual dysfunction do not target all aspects of sexual dysfunction, which leads to recurrence of the condition. Moreover, these existing treatments have been reported to have side effects or not be very comfortable to use. Therefore, there is an unaddressed industrial need to provide safe and efficient products in the therapeutic management of male sexual dysfunction by targeting all pathophysiological aspects of sexual dysfunction. The present invention solves the above problems by disclosing a composition comprising plant extracts and plant compounds for use as an aphrodisiac and in the therapeutic management of male sexual dysfunction and related disorders.

[0008] The principal object of the present invention is to disclose a composition comprising a 60 - 65 w / w% Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide for use as an aphrodisiac, a 12 - 18 w / w% Mucana pruriens extract standardized to contain 10 w / w% L - dopa, a 5 - 10 w / w% Coleus forskohlii extract standardized to contain 10 w / w% forskolin, a 12 - 18 w / w% Kaempferia parviflora standardized to contain 2.5 w / w% 5,7 - dimethoxyflavone and 10 w / w% or more total fand, and a 0.1 - 2 w / w% Piper nigrum extract standardized to contain 95 w / w% piperine.

[0009] Another object of the present invention is a 60 - 65 w / w% Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide, a 12 - 18 w / w% Mucana pruriens extract standardized to contain 10 w / w% L - dopa, a 5 - 10 w / w% Coleus forskohlii extract standardized to contain 10 w / w% forskolin, a 12 - 18 w / w% Kaempferia parviflora standardized to contain 2.5 w / w% 5,7 - dimethoxyflavone and 10 w / w% or more total flavonoids, and a 0.1 - 2 w / w% Piper nigrum extract standardized to contain 95 w / w% piperine, and to disclose a method for the therapeutic management of male sexual dysfunction and related disorders using the composition containing the same. The present invention solves the above - mentioned objects and provides further related advantages.

Summary of the Invention

[0010] The present invention provides a composition for the therapeutic management of male sexual dysfunction and related disorders.

[0011] More specifically, the present invention provides a standardized 60 - 65 w / w% Withania somnifera extract containing 0.25% withaferin and 7% withanolide, a standardized 12 - 18 w / w% Mucana pruriens extract containing 10 w / w% L - dopa, a standardized 5 - 10 w / w% Coleus forskohlii extract containing 10 w / w% forskolin, a standardized 12 - 18 w / w% Kaempferia parviflora containing 2.5 w / w% 5,7 - dimethoxyflavone and 10 w / w% or more total flavonoids, and a standardized 0.1 - 2 w / w% Piper nigrum extract containing 95 w / w% piperine, which composition increases the levels of nitric oxide, testosterone, and cGMP for use as an aphrodisiac. Other features and advantages of the present invention will become apparent from the following more detailed description taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention.

Brief Description of the Drawings

[0012]

Figure 1

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Figure 7

[0013] For a better understanding of the present invention and to enable a person skilled in the art to make and implement the present invention, the present invention will be described in detail by means of each preferred embodiment. In a most preferred embodiment, the present invention discloses a composition comprising 60 - 65 w / w% Withania somnifera extract, 12 - 18 w / w% Mucana pruriens extract, 5 - 10 w / w% Coleus forskohlii extract, 12 - 18 w / w% Kaempferia parviflora extract, and 0.1 - 2 w / w% Piper nigrum extract. In related aspects, the composition comprises at least one phytochemical selected from the group consisting of phosphodiesterase 5 (PDE-5) inhibitors; testosterone enhancers, nitric oxide enhancers, cGMP enhancers, antispasmodics and vasodilators, androgen receptor activators, and cGMP protein kinase activators.

[0014] In related aspects, Withania somnifera extract is standardized to contain 0.25% withaferin and 7% withanolide. In another related aspect, Mucana pruriens extract is standardized to contain 10 w / w% L-dopa. In yet another related aspect, Coleus forskohlii extract is standardized to contain 10 w / w% forskolin. In another related aspect, Kaempferia parviflora extract is standardized to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids.

[0015] In another preferred embodiment, the present invention discloses a composition for use as an aphrodisiac, comprising a 60 - 65 w / w% Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide, a 12 - 18 w / w% Mucana pruriens extract standardized to contain 10 w / w% L-dopa, a 5 - 10 w / w% Coleus forskohlii extract standardized to contain 10 w / w% forskolin, a 12 - 18 w / w% Kaempferia parviflora standardized to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids, and a 0.1 - 2 w / w% Piper nigrum extract standardized to contain 95 w / w% piperine. In related aspects, the composition comprises at least one phytochemical selected from the group consisting of phosphodiesterase 5 (PDE-5) inhibitors; testosterone boosters, nitric oxide boosters, cGMP boosters, antispasmodics and vasodilators, androgen receptor activators, and cGMP protein kinase activators. In another related aspect, the composition is formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and is administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, or food products.

[0016] In another preferred embodiment, the present invention is a method for increasing libido in a mammal, comprising administering to a mammal in need of such an effect an effective dose of a composition comprising a Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide, 60-65 w / w% based on the weight of the mammal; a Mucana pruriens extract standardized to contain 10 w / w% L-dopa, 12-18 w / w%; a Coleus forskohlii extract standardized to contain 10 w / w% forskolin, 5-10 w / w%; a Kaempferia parviflora standardized to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids, 12-18 w / w%; and a Piper nigrum extract standardized to contain 95 w / w% piperine, 0.1-2 w / w%. In a related aspect, the composition comprises at least one phytochemical selected from the group consisting of a phosphodiesterase 5 (PDE-5) inhibitor; a testosterone enhancer, a nitric oxide enhancer, a cGMP enhancer, an antispasmodic and vasodilator, an androgen receptor activator, and a cGMP protein kinase activator. In a related aspect, the effective dose of the composition is 50-200 mg / kg body weight. In another related aspect, the mammal is preferably male. In another related aspect, the mammal is preferably human. In another related aspect, the composition is formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and is administered in the form of a tablet, capsule, syrup, gummy, powder, suspension, emulsion, chewable, candy, or food product.

[0017] In yet another preferred embodiment, the present invention is a method for the therapeutic management of male sexual dysfunction and related disorders in mammals, comprising administering to a mammal in need of such an effect an effective dose of a composition comprising a 60 - 65 w / w% Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide, a 12 - 18 w / w% Mucana pruriens extract standardized to contain 10 w / w% L - dopa, a 5 - 10 w / w% Coleus forskohlii extract standardized to contain 10 w / w% forskolin, a 12 - 18 w / w% Kaempferia parviflora standardized to contain 2.5 w / w% 5,7 - dimethoxyflavone and 10 w / w% or more total flavonoids, and a 0.1 - 2 w / w% Piper nigrum extract standardized to contain 95 w / w% piperine. In related aspects, the male sexual disorder is selected from the group including erectile dysfunction, premature ejaculation, retarded ejaculation or anejaculation, and decreased libido. In related embodiments, the male sexual disorder is preferably erectile dysfunction and decreased libido. In related aspects, the management of male sexual dysfunction is brought about by inhibiting phosphodiesterase 5 (PDE - 5), increasing the levels of testosterone, nitric oxide, and cGMP, and activating androgen receptors and cGMP protein kinase. In related aspects, the effective dose of the composition is 50 - 200 mg / kg body weight. In another related aspect, the mammal is preferably male. In another related aspect, the mammal is preferably human. In another related aspect, the composition is formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and is administered in the form of tablets, capsules, syrups, gums, powders, suspensions, emulsions, chewables, candies, or food products. Specific exemplary examples referring to the most preferred embodiments are included below in this specification.

Example

[0018] (Example 1) Details of the composition The present invention discloses a synergistic composition comprising 60 - 65 w / w% of Withania somnifera extract, 12 - 18 w / w% of Mucana pruriens extract, 5 - 10 w / w% of Coleus forskohlii extract, 12 - 18 w / w% of Kaempferia parviflora extract, and 0.1 - 2 w / w% of Piper nigrum extract. Details and the intended therapeutic potential in the management of male sexual dysfunction of the individual plant extracts are provided below.

[0019] Withania somnifera, commonly known as ashwagandha, Indian ginseng, poison gooseberry, or winter cherry, is a plant in the Solanaceae family. Synonyms for Withania somnifera include Physalis somnifera L., Withania kansuensis Kuang & A. M. Lu, and Withania microphysalis. The main plant compound components are withanolides, which are triterpenoid lactones, mainly withanolide, withaferin A, alkaloids, steroidal lactones, tropine, and cuscohygrine ("Ashwagandha". Drugs.com. 2009. Retrieved 27 December 2018). The alkaloids of Withania somnifera have been reported to increase the production of nitric oxide and improve vascular endothelial abnormalities. The sterols present in the extract stimulate sexual and adrenal functions (Kumar et.al., Chemistry and pharmacology of withania somnifera: An update, TANG Humanitas Medicine, 2015; 5(1):1-13), and the flavonoids help protect the cardiovascular system (Narinderpal et.al.,A Review on Pharmacological Profile of Withania somnifera (Ashwagandha), Research & Reviews: Journal of Botanical Sciences, 2013; 2(4); 1-9).

[0020] Mucana pruriens is commonly known as velvet bean, Bengal velvet bean, Florida velvet bean, Mauritius velvet bean, yokohama velvet bean, cowage, cowitch, lacuna bean, and Lyon bean. It is a tropical leguminous plant native to Africa and tropical Asia and is widely naturalized and cultivated. The seeds of the plant contain L-Dopa, along with trace amounts of serotonin, nicotine, and bufotenine. The plant and its extracts have long been used in tribal communities as toxin antagonists against various bites. Furthermore, it has also been used in traditional Ayurvedic Indian medicine to treat diseases such as Parkinson's disease (Cilia et. al., Mucana Pruriens in Parkinson disease, Neurology, 2017 Aug 1; 89(5): 432-438). Levodopa, or L-dopa, present in the seeds of the plant is essential for the synthesis of dopamine, a neurotransmitter that plays an important role in sexual arousal. L-dopa has been reported to help prolong the duration of sexual intercourse and address premature ejaculation symptoms (Morales et. al. Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment - topical versus systemic, Canadian Urological Association Journal, 2012; 6(5) 380-385).

[0021] Piper nigrum is a flowering vine in the Piperaceae family, cultivated for its fruit, which is usually dried and used as a spice and seasoning. The fruit contains many terpenes, including germacrene, limonene, pinene, and α - and β - caryophyllene (Pund et. al. Nanoarchitectures for Neglected Tropical Protozoal Diseases: Challenges and State of the Art, Science Direct, 2016). Additionally, black pepper has been reported to contain piperine, which is used as a bioavailability enhancer (Kesarwani et. al. Bioavailability enhancers of herbal origin: An overview, Asia Pacafic Journal of Topical Biomedicine, 2013; 3(4) 253 - 266). Furthermore, piperine has been reported to increase the level of CoQ10 in the blood, causing blood flow to the whole body, including the penile veins.

[0022] Coleus forskohlii, also known as Plectranthus barbatus, is a tropical perennial plant related to typical Coleus species. It produces forskolin, an extract useful for pharmaceutical preparations. In Ayurveda, Coleus is used to treat heart diseases, spasm pain, dysuria, and spasms (Meghwal et. al. Nutritional Constituent of Black pepper as Medicinal Modules: A Review. Open Access Scientific Reports, 2012, 1(1) 1-7). Forskolin has been reported to increase cAMP, androgen receptor activity, and promote steroidogenesis. Additionally, forskolin enhances the sensitivity of androgen receptors, thereby increasing the availability of testosterone (Neto et. al. Vasodilation induced by forskolin involves cyclic GMP production. Journal of Biophysical Chemistry, 2011 2(4), 1-7).

[0023] Kaempferia parviflora, also known as Thai black ginger, Thai ginseng, or krachai dum, is a herbaceous plant of the Zingiberaceae family. Kaempferia parviflora has pharmacological activities such as anti-inflammatory activity, antioxidant activity, aphrodisiac activity, anti-ulcer effect, antiplasmodial activity, antifungal activity, and antibacterial activity. Kaempferia parviflora has been reported to contain many flavonoids, and they are responsible for its therapeutic potential. The plant is known to inhibit PDE5, activate cGMP protein kinase, resulting in a decrease in the concentration of Ca+, and promote smooth muscle relaxation in the smooth muscle of the penis (Chen et.al. Kaempferia parviflora and its methoxyflavone: Chemistry and Biological Activities. Evidence-Based Complementary and Alternative Medicine; 2018; Article ID 4057456, 1-15).

[0024] The compositions disclosed in the present invention target all mechanisms of male reproductive ability and provide a synergistic effect. The components of the composition are shown in Table 1. [Table 1]

[0025] (Example 2) Reproductive performance test The composition of the present invention was experimented on male wistar rats and observed for reproductive performance tests. Both behavioral evaluation and biochemical evaluation were carried out, and examples are used in the detailed description of the present invention to explain the findings that support the present invention described in the claims.

[0026] Behavioral evaluation Mounting behavior

Table 2

[0027] Non-estrous female rats were mated with males treated with a single dose of the formulation. The sexual behavior of the animals was observed for 3 hours (acute effect) (Tajuddin et. al., Aphrodisiac activity of 50% ethanol extracts of Myristica fragrans Houtt. (Nutmeg) and Syzygium aromaticum (L.) Merr. & Perry. (Clove) in male mice: a comparative study. BMC Complement Altern Med. 2003;3:6.). The number of mounts accompanied by other courtship activities was observed and recorded for 15 minutes at the start of the first hour. The females were separated for 105 minutes. They were mated again, and the number of mounts was observed for 15 minutes (at the 3rd hour). The results are summarized in Table 2 and Figure 1. Table 2: Effect of the formulation on the mounting behavior of male Wistar rats (long-term effect) The values in parentheses indicate the percentage increase relative to the control. The formulation significantly increased the number of mounts, indicating that the formulation is a very effective aphrodisiac.

[0028] Assessment of copulation: One hour after drug administration to one male, five estrous females were placed in the cage and maintained overnight. The next morning, vaginal smears of each female rat were examined by light microscopy for the presence of sperm. The stage of the estrous cycle was determined according to the evaluation criteria described by Dewsbury DA et. al., Effect of reserpine on the copulatory behaviour of Male rats. Physiol Behav. 1970;5:1331-1333; Szechtman H, Moshe H, et.al. Sexual behaviour Pain sensitivity and stimulates endogenous opioid in male rats. Eur J Pharmacol. 1981;70:279-285. The results are listed in Table 3.

[0029]

Table 3

[0030] Observation of the Coolidge effect of the formulation in male Wistar rats The Coolidge effect is the phenomenon in which a male's sexual interest is restored when a new female is introduced, even after a period of sexual rest with a previous, but still available, sexual partner. The effect in male Wistar rats was identified by the procedures described in Reber, A. S. & Reber, E., The Penguin dictionary of psychology (3rd ed.), London: Penguin; Brown, R. E. (1974), "Sexual arousal, the Coolidge effect and dominance in the rat (Rattus norvegicus)", Animal Behaviour, 22 (3): 634-637; Lester, GL; Gorzalka, BB (1988), "Effect of novel and familiar mating partners on the duration of sexual receptivity in the female hamster", Behavioral Neural Biology, 49 (3): 398-405; Pinel, John (2007), Biopsychology (6th ed.), Boston: Pearson Allyn and Bacon. Six hours after drug treatment, all females were replaced with newly estrous females for the next six hours.

[0031] To confirm copulation and ejaculation in the first set of females and the Coolidge effect in the second set of females, vaginal smears from all females were observed under an optical microscope. Table 4 shows the percentage increase in the number of pregnant female rats relative to the control sample and the percentage rate of increase between the first set of females and the set of females they were replaced with.

[0032]

Table 4

[0033] The electrical barrier effect on sexual behavior The experimental procedure for observing the electrical barrier effect on sexual behavior was carried out as described by Graham JH et. al., Inhibitory avoidance behavior and memory assessment 2001. In Buccafusco JJ (ed.), methods of Behavior analysis in Neuroscience, p.141-151. Boca Raton: CRC Press. In this experiment, receptive (estrous) females were kept on one side of the cage and male rats treated with the test sample were kept on the opposite side of the same cage. During that time, an electrical barrier was placed. A foot shock was given through the floor grid. Observations were recorded for both the treated group and the control group regarding the tendency of male rats to cross the barrier. The results are listed as Table 5.

[0034]

Table 5

[0035] Biochemical evaluation Evaluation of testosterone Testosterone is the main male hormone produced by the interstitial (Leydig) cells of the male testes and is also produced in small amounts by the adrenal glands. Testosterone in males is responsible for maintaining the reproductive system and secondary sexual characteristics throughout the male's life. The treatment group was given the formulation and the levels were measured 1 hour and 3 hours later according to the standard protocol.

[0036] The data show an increase in serum testosterone concentration 1 hour and 3 hours after treatment in the treated animals (Figure 2). Table 6 shows the percentage of active testosterone relative to the control over 21 days.

Table 6

[0037] Androstenedione evaluation: Androstenedione is a steroid hormone that mainly acts as a precursor in the production of testosterone and estrogen in the body. Males with too little androstenedione may not be able to develop puberty-related sexual characteristics, including pubic and body hair, genital growth, and deepening of the voice. Androstenedione was evaluated according to a standard protocol.

[0038] The results showed an increase in serum androstenedione concentration in the treated animals 1 hour after administration of the formulation (Figure 3). Table 7 shows the percentage of androstenedione activity relative to the control over 21 days. [Table 7]

[0039] Nitric oxide evaluation: The signaling molecule nitric oxide (NO) is released from nerve endings or endothelial cells and activates a cascade reaction that ultimately causes an increase in the intracellular concentration of cGMP (cyclic guanosine monophosphate). This secondary messenger molecule causes a series of events leading to smooth muscle relaxation due to a decrease in intracellular calcium ion concentration. Clinically important inhibitors (sildenafil, vardenafil, and tadalafil) all act to promote smooth muscle relaxation by their ability to accumulate cGMP when nitric oxide is released, similar to the presence of sexual stimulation.

[0040] Nitric oxide in the serum of male Wistar rats was evaluated by ELISA. The method used was as per the procedure described by Miles et. al. Determination of nitric oxide using fluorescence spectroscopy. Methods Enzymol.1996; 268:105-20. The results showed an increase in serum nitric oxide concentration in the treated animals 1 hour after administration of the formulation (Figure 8).

Table 8

[0041] Evaluation of cGMP and cGMP-specific protein kinase The levels of cGMP and cGMP-specific protein kinase in the serum of male Wistar rats were also evaluated. The results showed an increase in serum cGMP concentration (Figure 4) and cGMP-PK1 concentration (Figure 5) in the treated animals 1 hour after administration of the formulation.

[0042] The comparative effects of individual components and formulations on cGMP and cGMP-specific protein kinase were evaluated. The results showed a synergistic effect on serum cGMP concentration (Figure 6) and cGMP-PK1 concentration (Figure 7) in the treated animals 1 hour after administration of the test drug, when compared with the expression of cGMP in the groups treated with individual components.

[0043] (Example 3) Cardiovascular function test The purpose of this test in rats was to identify the effect of the test substance on the cardiovascular system in experimental rats when administered duodenally. When administered duodenally to male Wistar rats under anesthesia with normal blood pressure at three different doses (50, 100, and 200 mg / kg), the formulation showed no effect (increase or decrease) on blood pressure, heart rate, and respiration. Observations were made at 1-hour intervals for up to 3 hours after drug administration. No changes were observed at any time interval for all three parameters at the stepwise doses.

[0044] The results are summarized in Tables 9 - 11.

Table 9

[0045]

Table 10

[0046]

Table 11

[0047] Other changes and modifications to the present invention will be apparent to those skilled in the art from the foregoing disclosure and teachings. Accordingly, while only certain specific embodiments of the present invention have been specifically described herein, it is obvious that numerous changes may be made without departing from the spirit and scope of the present invention. The scope of the present invention should be construed only in connection with the appended claims. Preferred embodiments of the present invention are as follows. 〔1〕A composition for use as an aphrodisiac, comprising a Withania somnifera extract standardized to contain 60 - 65 w / w% so as to contain 0.25% withaferin and 7% withanolide, a Mucana pruriens extract standardized to contain 12 - 18 w / w% so as to contain 10 w / w% L-dopa, a Coleus forskolii extract standardized to contain 5 - 10 w / w% so as to contain 10 w / w% forskolin, a Kaempferia parviflora standardized to contain 12 - 18 w / w% so as to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids, and a Piper nigrum extract standardized to contain 0.1 - ~2 w / w% so as to contain 95 w / w% piperine. 〔2〕The composition according to 〔1〕above, comprising at least one plant compound selected from the group consisting of phosphodiesterase 5 (PDE-5) inhibitors, testosterone enhancers, nitric oxide enhancers, cGMP enhancers, antispasmodics and vasodilators, androgen receptor activators, and cGMP protein kinase activators. 〔3〕The composition according to 〔1〕above, formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, or food products. 〔4〕A method for enhancing the sexual desire of a mammal, comprising administering to a mammal in need of an effect of enhancing sexual desire an effective dose of a composition comprising a Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide at 60 - 65 w / w% based on the weight of the mammal, a Mucana pruriens extract standardized to contain 10 w / w% L-dopa at 12 - 18 w / w%, a Coleus forskolii extract standardized to contain 10 w / w% forskolin at 5 - 10 w / w%, a Kaempferia parviflora standardized to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids at 12 - 18 w / w%, and a Piper nigrum extract standardized to contain 95 w / w% piperine at 0.1 - 2 w / w%. 〔5〕The method according to 〔4〕 above, wherein the composition comprises at least one plant compound selected from the group consisting of phosphodiesterase 5 (PDE-5) inhibitors; testosterone enhancers, nitric oxide enhancers, cGMP enhancers, antispasmodics and vasodilators, androgen receptor activators, and cGMP protein kinase activators. 〔6〕The method according to 〔4〕 above, wherein the effective dose of the composition is 50 - 200 mg / kg body weight. 〔7〕The method according to 〔4〕 above, wherein the mammal is preferably male. 〔8〕The method according to 〔4〕 above, wherein the mammal is preferably human. 〔9〕The method according to 〔4〕 above, wherein the composition is formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and is administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, or food products. 〔10〕A method for the therapeutic management of male sexual dysfunction and related disorders in mammals, comprising administering to a mammal in need of a therapeutic management effect for male sexual dysfunction and related disorders an effective dose of a composition comprising a 60 - 65 w / w% Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide based on the body weight of the mammal, a 12 - 18 w / w% Mucana pruriens extract standardized to contain 10 w / w% L - dopa, a 5 - 10 w / w% Coleus forskolii extract standardized to contain 10 w / w% forskolin, a 12 - 18 w / w% Kaempferia parviflora standardized to contain 2.5 w / w% 5,7 - dimethoxyflavone and 10 w / w% or more total flavonoids, and a 0.1 - 2 w / w% Piper nigrum extract standardized to contain 95 w / w% piperine. 〔11〕The method according to 〔10〕 above, wherein the male sexual disorder is selected from the group including erectile dysfunction, premature ejaculation, retarded ejaculation or ejaculatory difficulty, and hypoactive sexual desire. 〔12〕The method according to 〔10〕 above, wherein the male sexual disorder is preferably erectile dysfunction and hypoactive sexual desire. 〔13〕The method according to 〔10〕 above, wherein the management of the male sexual dysfunction is brought about by inhibiting phosphodiesterase 5 (PDE - 5), increasing the levels of testosterone, nitric oxide, and cGMP, and activating androgen receptors and cGMP protein kinase. 〔14〕The method according to 〔10〕 above, wherein the effective dose of the composition is 50 - 200 mg / kg body weight. 〔15〕The method according to 〔10〕 above, wherein the mammal is preferably male. 〔16〕The method according to 〔10〕 above, wherein the mammal is preferably human. 〔17〕The method according to 〔10〕 above, wherein the composition is formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and is administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, or food products.

Claims

1. A composition for use as an aphrodisiac in male mammals, comprising: a 60 - 65 w / w% Withania somnifera extract containing 0.25% withaferin and 7% withanolide; a 12 - 18 w / w% Mucuna pruriens extract containing 10 w / w% L - dopa; a 5 - 10 w / w% Coleus forskolii extract containing 10 w / w% forskolin; a 12 - 18 w / w% Kaempferia parviflora extract containing 2.5 w / w% 5,7 - dimethoxyflavone and 10 w / w% or more total flavonoids; and a 0.1 - 2 w / w% Piper nigrum extract containing 95 w / w% piperine.

2. The composition according to claim 1, comprising at least one plant compound selected from the group consisting of phosphodiesterase 5 (PDE - 5) inhibitors, testosterone enhancers, nitric oxide enhancers, cGMP enhancers, antispasmodics and vasodilators, androgen receptor activators, and cGMP protein kinase activators.

3. The composition according to claim 1, formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and administered in the form of tablets, capsules, syrups, gums, powders, suspensions, emulsions, chewables, candies, or food products. **Claim 4**: A composition for enhancing the sexual desire of male mammals, wherein the composition comprises a 60 - 65 w / w% Withania somnifera extract containing 0.25% withaferin and 7% withanolide, a 12 - 18 w / w% Mucuna pruriens extract containing 10 w / w% L - dopa, a 5 - 10 w / w% Coleus forskolii extract containing 10 w / w% forskolin, a 12 - 18 w / w% Kaempferia parviflora extract containing 2.5 w / w% 5,7 - dimethoxyflavone and 10 w / w% or more total flavonoids, and a 0.1 - 2 w / w% Piper nigrum extract containing 95 w / w% piperine, and based on the body weight of the mammal, the effective dose of the composition is administered to a mammal in need of an effect of enhancing sexual desire. **Claim 5** The composition according to claim 4, wherein the composition comprises at least one plant compound selected from the group consisting of phosphodiesterase 5 (PDE - 5) inhibitors, testosterone enhancers, nitric oxide enhancers, cGMP enhancers, antispasmodics and vasodilators, androgen receptor activators, and cGMP protein kinase activators. **Claim 6** The composition according to claim 4, wherein the effective dose of the composition is 50 - 200 mg / kg body weight. **Claim 7** The composition according to claim 4, wherein the mammal is a human. **Claim 8** The composition according to claim 4, wherein the composition is formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and is administered in the form of tablets, capsules, syrups, gums, powders, suspensions, emulsions, chewables, candies, or food products. **Claim 9** A composition for the therapeutic management of male sexual dysfunction and related disorders in mammals, said composition comprising a 60-65 w / w% Withania somnifera extract containing 0.25% withaferin and 7% withanolide, a 12-18 w / w% Mucuna pruriens extract containing 10 w / w% L-dopa, a 5-10 w / w% Coleus forskolii extract containing 10 w / w% forskolin, a 12-18 w / w% Kaempferia parviflora extract containing 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids, and a 0.1-2 w / w% Piper nigrum extract containing 95 w / w% piperine, wherein, based on the body weight of the mammal, an effective dose of said composition is administered to a mammal in need of therapeutic management of male sexual dysfunction and related disorders.

10. The composition according to claim 9, wherein the male sexual dysfunction is selected from the group comprising erectile dysfunction, premature ejaculation, retarded ejaculation, or ejaculation difficulty, and decreased libido.

11. The composition according to claim 9, wherein the male sexual dysfunction is erectile dysfunction and decreased libido.

12. The composition according to claim 9, wherein the management of the male sexual dysfunction is brought about by inhibiting phosphodiesterase 5 (PDE-5), increasing the levels of testosterone, nitric oxide, and cGMP, and activating androgen receptors and cGMP protein kinase.

13. The composition according to claim 9, wherein the effective dose of said composition is 50-200 mg / kg body weight.

14. The composition according to claim 9, wherein the mammal is a human.

15. The composition according to claim 9, wherein the composition is formulated with a pharmaceutically / nutritionally acceptable excipient, adjuvant, diluent, or carrier and is administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, or food products. Use of Withania somnifera extract, Mucuna pruriens extract, Coleus forskolii extract, Kaempferia parviflora extract and Piper nigrum extract in the manufacture of a composition for enhancing the sexual desire of male mammals, wherein the composition comprises 60 - 65 w / w% of Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide, 12 - 18 w / w% of Mucuna pruriens extract standardized to contain 10 w / w% L-dopa, 5 - 10 w / w% of Coleus forskolii extract standardized to contain 10 w / w% forskolin, 12 - 18 w / w% of Kaempferia parviflora extract standardized to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids, and 0.1 - 2 w / w% of Piper nigrum extract standardized to contain 95 w / w% piperine, and based on the body weight of the mammal, the effective dose of the composition is administered to a mammal in need of an effect of enhancing sexual desire. A method for enhancing the sexual desire of male non-human mammals, comprising administering to a non-human mammal in need of an effect of enhancing sexual desire an effective dose of a composition comprising: a Withania somnifera extract standardized to contain 60-65 w / w% of withaferin A and 7% of withanolide based on the body weight of the non-human mammal; a Mucuna pruriens extract standardized to contain 12-18 w / w% of L-dopa; a Coleus forskolii extract standardized to contain 5-10 w / w% of forskolin; a Kaempferia parviflora extract standardized to contain 2.5 w / w% of 5,7-dimethoxyflavone and 10 w / w% or more of total flavonoids; and a Piper nigrum extract standardized to contain 95 w / w% of piperine in an amount of 0.1-2 w / w%. Claim 18 Use of Withania somnifera extract, Mucuna pruriens extract, Coleus forskolii extract, Kaempferia parviflora extract and Piper nigrum extract in the manufacture of a composition for the therapeutic management of male sexual dysfunction and related disorders, wherein the composition comprises a 60-65 w / w% Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide, a 12-18 w / w% Mucuna pruriens extract standardized to contain 10 w / w% L-dopa, a 5-10 w / w% Coleus forskolii extract standardized to contain 10 w / w% forskolin, a 12-18 w / w% Kaempferia parviflora extract standardized to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids, and a 0.1-2 w / w% Piper nigrum extract standardized to contain 95 w / w% piperine, and wherein the effective dose of the composition is administered to a mammal in need of a therapeutic management effect for male sexual dysfunction and related disorders, based on the body weight of the mammal.

19. A method for the therapeutic management of male sexual dysfunction and related disorders in non-human mammals, comprising administering to a non-human mammal in need of therapeutic management of male sexual dysfunction and related disorders an effective dose of a composition comprising: a 60-65 w / w% Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolide, based on the body weight of the non-human mammal; a 12-18 w / w% Mucuna pruriens extract standardized to contain 10 w / w% L-dopa; a 5-10 w / w% Coleus forskolii extract standardized to contain 10 w / w% forskolin; a 12-18 w / w% Kaempferia parviflora extract standardized to contain 2.5 w / w% 5,7-dimethoxyflavone and 10 w / w% or more total flavonoids; and a 0.1-2 w / w% Piper nigrum extract standardized to contain 95 w / w% piperine.

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