Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/88—Liliopsida (monocotyledons)
  • A61K36/906—Zingiberaceae (Ginger family)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
  • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration

Definitions

• compositions for the therapeutic management of male sexual dysfunction and associated disorders relate to compositions comprising plant extracts and phytochemical for the management of disorders related to male sexual dysfunction.
• the common types of male sexual dysfunction include erectile dysfunction, premature ejaculation, delayed or inhibited ejaculation, and reduced libido.
• a combination of physical and physiological issues can cause sexual dysfunction in males, particularly erectile dysfunction.
• the brain plays a key role in triggering the series of physical events that cause an erection, starting with feeling of sexual excitement. Depression, anxiety or other mental health conditions, stress or relationship problems due to stress, poor communication causes or worsens erectile dysfunction.
• Penile erection is a complex process involving psychogenic and hormonal functionality and a neurovascular non adrenergic, non cholinergic mechanism.
• Nitrous oxide, produced by Corpora cavernosa is the main vasoactive noncholinergic and non adrenergic neurotransmitter and chemical mediator of erectile function.
• Nitric oxide stimulates the enzyme guanylate cyclase that converts GTP to 3’, 5’- cyclic guanosine monophosphate (cGMP).
• cGMP causes smooth muscles in the arteries to relax which increases the blood flow to the penis.
• the veins that cany blood away from the penis constrict, thus trapping the pressurized blood in the Corpora cavernosa resulting in the erection.
• the cGMP level plays major role in maintaining the erection for longer time.
• the cGMP is converted into 5’ GMP by phospho diesterase enzyme, thus reducing the erection.
• Inhibition of Phospho diesterase enzyme can prolong the erection of the penis providing sexual satisfaction (Please provide reference)
• composition comprising botulinum toxin mainly onabotulinum toxin A, abobotulinumtoxin A and incobotulinumtoxin A: PDE5 inhibitors mainly sildenafil citrate, lodenafil, avanafil, mirodenafil, sildeafil, tadalafil and other derivatives for simultaneous, sequential or separate use in the treatment of erectile functions.
• PDE5 inhibitors mainly sildenafil citrate, lodenafil, avanafil, mirodenafil, sildeafil, tadalafil and other derivatives for simultaneous, sequential or separate use in the treatment of erectile functions.
• US patent number 7,147,874 discloses pharmaceutical composition for the prevention and treatment of premature ejaculation and/or hypersensitivity of sexual stimulation are provided.
• the composition contains purified sumsoo extract and purified ginseng extract containing saponin as the main component, without other herbal essential oil components.
• [Para 0011]US 2006/0269623 teaches about herbal compositions and methods of treatment for prevention or treatment of erectile dysfunction disorders and ameliorating symptoms thereof and as a preventative measure against erectile dysfunction.
• the methods comprise administering a therapeutically effective composition of matter comprising the following herbal and other components: 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.
• the present invention solves the above problem by disclosing a composition comprising plant extracts and phytochemical for use as an aphrodisiac and in the therapeutic management of male sexual dysfunction and related disorders.
• It is another object of the invention to disclose a method for the therapeutic management of male sexual dysfunction and related disorders using a composition comprising 60-65% w/w Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolides, 12-18% w/w Mucana pruriens extract standardized to contain 10% w/w L- dopa, 5-10% w/w Coleus forskohlii extract standardized to contain 10% w/w forskolin, 12- 18% w/w Kaempferia parviflora standardized to contain 2.5% w/w of 5,7-dimethoxyflavone and not less than 10% w/w Total flavonoids and 0.1 - 2% w/w Piper nigrum extract standardized to contain 95% w/w Piperine.
• the present invention provides a composition for the therapeutic management of male sexual dysfunction and related disorders.
• composition comprising 60-65% w/w Withania somnifera extract standardized to contain 0.25% withaferin and 7%
• Fig. 1 is a graphical representation showing the effect of the formulation on mounting behavior in male wistar rats (long term effect).
• Fig. 2 is a graphical representation of serum testosterone levels in male wistar rats administered with different concentrations of the formulation.
• Fig. 3 is a graphical representation showing the serum androstenedione levels in male wistar rats administered with different concentrations of the formulation.
• Fig. 4 is a graphical representation showing the levels of serum cGMP in male wistar rats administered with different concentrations of the formulation.
• Fig. 5 is a graphical representation showing the levels of serum cGMP specific kinase in male wistar rats administered w ith different concentrations of the formulation.
• Fig. 6 is a graphical representation showing the comparative evaluation of the effect of formulation and individual plant actives on the levels of serum cGMP in male wistar rats
• Fig. 7 is a graphical representation showing the comparative evaluation of the effect of formulation and individual plant actives on the levels of serum cGMP specific kinase in male wistar rats.
• the present invention discloses a composition
• 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% w7w Kaempferia parviflora extract and 0.1 - 2% w/w Piper nigrum extract.
• the composition comprises at least one phytochemical selected from the group of phospho diesterase 5 (PDE-5) inhibitor; testosterone enhancer, Nitric oxide enhancer, cGMP enhancer, anti-spasmodic and vasodilator, androgen receptor activator and cGMP protein kinase activator.
• PDE-5 phospho diesterase 5
• the Withania somnifera extract is standardized to contain 0.25% withaferin and 7% withanolides.
• the Mucana pruriens extract is standardized to contain 10% w/w L-dopa.
• the Coleus forskohlii extract is standardized to contain 10% w/w forskolin.
• the Kaempferia parviflora extract is standardized to contain 2.5% w/w of 5,7-dimethoxyflavone and not less than 10% w/w Total flavonoids.
• the invention discloses a composition
• a composition comprising 60-65% w/w Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolides, 12-18% w/w Mucana pruriens extract standardized to contain 10% w/w L-dopa, 5-10% w/w Coleus forskohlii extract standardized to contain 10% w/w forskolin, 12-18% w/w Kaempferia parviflora standardized to contain 2.5% w/w of 5,7- dimethoxyflavone and not less than 10% w/w Total flavonoids and 0.1 - 2% w/w Piper nigrum extract standardized to contain 95% w/w Piperine for use as an aphrodisiac.
• the composition comprises at least one phytochemical selected from the group of phospho diesterase 5 (PDE-5) inhibitor; testosterone enhancer, Nitric oxide enhancer, cGMP enhancer, anti-spasmodic and vasodilator, androgen receptor activator and cGMP protein kinase activator.
• PDE-5 phospho diesterase 5
• the composition is formulated with pharmaceutically/nutraceutically acceptable excipients, adjuvant, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewable, candies or eatables.
• the invention discloses a method for increasing libido in mammals, said method comprising step of administering an effective dose of a composition, based on the body weight of the mammal, comprising 60-65% w/w Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolides, 12-18% w/w Mucana pruriens extract standardized to contain 10% w/w L-dopa, 5-10% w/w Coleus forskohlii extract standardized to contain 10% w/w forskolin, 12-18% w/w Kaempferia parviflora standardized to contain 2.5% w/w of 5,7-dimethoxyflavone and not less than 10% w/w Total flavonoids and 0.1 - 2% w/w Piper nigrum extract standardized to contain 95% w/w Piperine to mammals in need of such effect.
• a composition based on the body weight of the mammal, comprising 60-65% w/w With
• the composition comprises at least one phytochemical selected from the group of phospho diesterase 5 (PDE- 5) inhibitor; testosterone enhancer, Nitric oxide enhancer, cGMP enhancer, anti-spasmodic and vasodilator, androgen receptor activator and cGMP protein kinase activator.
• PDE-5 phospho diesterase 5
• the effect dose of the composition is 50-200 mg/kg body weight.
• the mammal is preferably male.
• the mammal is preferably human.
• composition is formulated with pharmaceutical ly/nutraceutically acceptable excipients, adjuvant, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewable, candies or eatables.
• the invention discloses a method for therapeutic management of male sexual dysfunction and related disorders in mammals, said method comprising step of administering an effective dose of a composition, based on the body weight of the mammal, comprising 60-65% w/w Withania somnifera extract standardized to contain 0.25% withaferin and 7% withanolides, 12-18% w/w Mucana pruriens extract standardized to contain 10% w/w L-dopa, 5-10% w/w Coleus forskohlii extract standardized to contain 10% w/w forskolin, 12-18% w/w Kaempferia parviflora standardized to contain 2.5% w/w of 5,7-dimethoxyfIavone and not less than 10% w/w Total flavonoids and 0.1 - 2% w/w Piper nigrum extract standardized to contain 95% w/w Piperine to mammals in need of such effect.
• the male sexual dysfunction is selected from the group comprising erectile dysfunction, premature ejaculation, Delayed or inhibited ejaculation, and reduced libido.
• the male sexual dysfunction is preferably erectile dysfunction and reduced libido.
• the management of male sexual dysfunction is brought about by inhibiting phospho diesterase 5 (PDE-5), enhancing testosterone, Nitric oxide and cGMP levels and activating androgen receptor and cGMP protein kinase.
• the effect dose of the composition is 50-200 mg/kg body weight.
• the mammal is preferably male.
• the mammal is preferably human.
• composition is formulated with pharmaceutically/nutraceutically acceptable excipients, adjuvant, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewable, candies or eatables.
• the present invention discloses a synergistic 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.
• the details and the intended therapeutic potential in the management of male sexual dysfunction of the individual plant extracts are provided below:
• Withania somnifera commonly known as ashwagandha, Indian ginseng, poison gooseberry or winter cherry is a plant in the Solanacea family.
• Synonyms for Withania somnifera are Physalis somnifera L., Withania kansuensis Kuang & A. M. Ln and Withania microphysalis .
• the main phytochemical component constitutes withanolides which are triterpene lactones mainly withanolides, withaferin A, alkaloids, steroidal lactones, tropine and cuscohygrine. (Ashwagandha”. Drugs.com. 2009. Retrieved 27 December 2018).
• the alkaloids of Withania somnifera are reported to increase 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 flavonoids aids in the protections of 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)
• Mucana pruriens commonly known as velvet bean, Bengal velvet bean, Florida velvet bean, Mauritius velvet bean, yokohama velvet bean, cowage co witch, lacuna bean and Lyon bean. It is a tropical legume native to Africa and tropical Asia and widely naturalizes and cultivated. Tire seeds of the plant contain L-Dopa, with trace amount of serotonin, nicotine and bufotenine. The plant and its extracts have been long used in tribal communities as a toxin antagonist for various snakebites. It has also been used in traditional ayurveda Indian medicine to treat diseases including 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 seed of the plant is vital for the synthesis of dopamine, a neurotransmitter that plays a important function in sexual arousal.
• L-dopa helps to prolong time of intercourse and is reported to address the symptoms of premature ejaculation.
• [Para 0041 ]Piper nigrum is a flowering vine in the family Piperaceae, cultivated for its fruit, which is usually dried and used as a spice and seasoning agent, the fruit contains many terpenes, including germacrene, limoline, pipene and alpha- phellandrene and beta- caryophyllene.
• Black pepper is also reported to contain Piperine which is used as a bioavailability enhancer.
• Piperine is also reported to increase the levels of CoQIO in the blood which triggers blood flow to the entire body including penile vein.
• Coleus for skohlii also known as Plectranthus barbatus is a tropical perennial plant related to the typical coleus species. It produces forskolin, an extract useful for pharmaceutical preparations. In ayurveda, Coleus is used to treat heart disease, spasmodic pain, painful urination and convulsions (Meghwal et. al. Nutritional Constituent of Black pepper as Medicinal Modules: A Review. Open Access Scientific Reports, 2012, 1(1) 1-7). Forskolin is reported to increase cAMP, androgen receptor activity and promote steroidogensis. Forskolin also increases androgen receptor sensitivity thereby increasing the utilization of testosterone (Neto et. al. Vasodilation induced by forskolin involves cyclic GMP production. Journal of Biophysical Chemistry, 2011 2(4), 1-7)
• Kaempferia parviflora also known as Thai black ginger, Thai ginseng or krachai dum, is an herbaceous plant in the family Zingiberaceae.
• K. parviflora has pharmacological activities such as anti-inflammatory, antioxidant, and aphrodisiac, anti gastric ulcer effect, antiplasmodial, antifungal, and antibacterial activities.
• K. parviflora is reported to contain many flavonoids which is responsible for its therapeutic potential. The plant is known for its PDE5 inhibition and activation of cGMP protein kinase which in turn decrease the concentration of Ca+ and accelerates smooth muscles relaxation in the penile smooth muscles (Chen et.al. Kaempferia parviflora and its methoxyflavone: Chemistry and Biological Activities. Evidence-Based Complementary and Alternative Medicine; 2018; Article ID 4057456, 1-15)
• composition disclosed in the invention targets all the mechanisms of male fertility and provides synergistic effects.
• the constituent of the composition is mentioned in table 1.
• Non- estrous female rats were paired with males treated with single dose of the formulation. Animals were observed for 3h (acute effect) for their sexual behavior (Tajuddin et. ah, Aphrodisiac activity of 50% ethanol extracts of Myristica ffagrans Houtt. (Nutmeg) and Syzygium aromaticum (L.) Merr. & Perry. (Clove) in male mice: a comparative study. BMC Complement Altern Med. 2003 ;3:6.). Number of mounts along with other courtship activities recorded during 15 min observation period at the start of 1st hour. Female separated for 105 minutes. Again introduced and number of mounts observed for 15 minutes (3rd h). The results are tabulated in Table 2 and Fig. 1.
• Coolidge effect is a phenomenon wherein males exhibit renewed sexual interest when a new female is introduced, even after cessation of sex with prior but still available sexual partners.
• the effect in male wistar rats was determined by the procedures laid down by Reber, A. S. & Reber, E., The Penguin dictionary of psychology (3rd ed.), London: Penguin: Brown, R. E.
• Testosterone is the principal male hormone produced by the interstitial ( Leydig ) cells of the male testes and in smaller amounts by the adrenals . Testosterone in males is responsible for maintenance of reproductive system and secondary sexual characters throughout the life of the male. The treated groups were given the formulation and levels were measured after lhr and 3 hr as per standard protocol.
• Androstenedione is a steroid hormone that mainly acts as a stepping stone in the manufacture of testosterone and estrogen within the body. Males with too little androstenedione may fail to develop the sexual characteristics associated with puberty, including pubic and body hair, growth of the sexual organs and deepening of the voice. Androstenedione was estimated as per standard protocol. [Para 0073] The results indicated an increase in androstenedione concentration in serum of treated animals after lhr of administration of the formulation (Fig. 3). Table 7 shows the Percentage activity of androstenedione against control over a period of 21 days.
• nitric oxide NO is released from nerve endings or from endothelial cells and activates a cascade reaction, which ultimately leads to an increased cellular concentration of cGMP (cyclic guanosine monophosphate).
• cGMP cyclic guanosine monophosphate
• This second messenger molecule induces a series of events that lead to smooth-muscle relaxation through a reduction in the intracellular calcium ion concentration.
• the clinically important inhibitors (sildenafil, vardenafil and tadalafil) all act to promote smooth-muscle relaxation by their ability to allow cGMP to accumulate when nitric oxide is released, as is the case when sexual stimulation is present.
• Nitric oxide was estimated in the serum of male wistar rats by ELISA. The method employed is as per the procedure described by Miles et. al. Determination of nitric oxide using fluorescence spectroscopy. Methods Enzymol.1996; 268: 105-20. The results indicated an increase in Nitric oxide concentration in serum of treated animals after lhr of administration of the formulation (Table 8). Table 8: Nitric oxide estimation in serum of male wistar rats by ELISA

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