Claims:I/We Claim:
1. A synergistic nutraceutical composition comprising, as active compounds: L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol and L-tryptophan for treating a symptom associated with erectile dysfunction and premature ejaculation in a subject suffering symptoms associated with Male Sexual Dysfunction.
2. The synergistic nutraceutical composition of claim 1 wherein said the composition further comprising Vitamin B6 for treating, preventing or improving male premature ejaculation and erectile dysfunction.
3. The synergistic nutraceutical composition of claim 1 wherein said the composition selected from solid and liquid oral pharmaceutical composition comprising L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, Vitamin B6 and L-tryptophan and one or more pharmaceutically acceptable excipients.
4. The synergistic nutraceutical composition of claim 3 wherein said the composition selected from tablet, hard gelatin capsule, soft gelatin capsule, pellets, microspheres, granules and powders.
5. The synergistic nutraceutical composition of claim 3 wherein said the liquid pharmaceutical composition selected from syrup, reconstitutable suspensions, syrups, elixirs and emulsions.
6. The synergistic nutraceutical composition of claim 3 wherein said the solid pharmaceutical composition with the pharmaceutically acceptable excipients may include one or more diluents, binders, disintegrants, glidants, lubricants, sweeteners/taste masking agents, compression aids, colorants and flavours and the like.
7. The synergistic nutraceutical composition of claim 5 wherein a liquid pharmaceutical composition with the pharmaceutically acceptable excipients may include one or more viscosity controlling agent, suspending agents, emulsifiers, solubilizers, buffers, sweeteners/taste masking agents, colorants and flavours and the like.
8. A sachet dosage form of nutraceutical composition comprising granules of active compounds selected from the L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol and L-tryptophan for treating, preventing or improving male premature ejaculation and erectile dysfunction wherein a combination of said active compounds exhibits synergy.
9. A sachet dosage form of claim 8 wherein said the composition further comprising Vitamin B6 for treating, preventing or improving male premature ejaculation and erectile dysfunction.
10. A sachet dosage form of claim 9 wherein said the composition prepared by a process comprising the steps of preparing a homogeneous mass by mixing L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, Vitamin B6 and L-tryptophan with a suitable binder, milling the mass and sizing to obtain granules, blending the granules of active ingredients and one or more pharmaceutically acceptable excipients; and filling into sachet dosage form.

, Description:FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

1. Title of the Invention
Nutraceutical supplement for Premature Ejaculation associated with Erectile Dysfunction

2. Applicant (s)
(a) Name: MMC Pharmaceuticals Ltd
(b) Nationality: Indian
(c) Address:
113, Visalakshi Street, Devi Karumariamman Nagar,
Valasaravakkam, Chennai,
India - 600 087
3. Preamble to the Description
The following specification particularly describes the invention and the manner in which it is to be performed.

Technical Field of the Invention
The present invention relates to a nutraceutical composition for prophylaxis and treatment of premature ejaculation and erectile dysfunction. More particularly, the present invention relates to synergistic nutraceutical composition comprising the combination of active ingredients such as L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6.
Background of the Invention
Sexual dysfunction can have a profound impact on an individual’s life and general well-being and has been associated with low self-esteem, mental health problems, interpersonal and intimacy problems, diminished sexual functioning and satisfaction and decreased quality of life.
The term premature ejaculation (PE) describes the phenomenon which occurs when ejaculation happens sooner (< 2 minutes) than a man or his partner would like during at least 50% of coital episodes; as also defined similarly by Masters and Johnson (Strassberg DS, Mahoney JM, Schaugaard M et al. The role of anxiety in premature ejaculation: A psychophysiological model. Arch Sex Behav 1990; 19(3): 251-257).
The World Health Organization (WHO, 1993) describes the PE as "the inability to delay ejaculation sufficient to enjoy lovemaking, which is manifested by either an occurrence of ejaculation before or very soon after the beginning of intercourse or ejaculation occurring in the absence of sufficient erection to make intercourse possible (El-Hamd MA, Saleh R & Majzoub A. Premature ejaculation: An update on definition and pathophysiology. Asian J Androl 2019; 21(5): 425-432).
PE has been documented to be the most common type of sexual disorders in men of all age groups. About 30% of men are affected but possibly up to 75%, as per some reviews, suffer from PE.
Organs and anatomical structures of the urogenital tract involved in ejaculation can be divided in two categories. Those that take part in emission include Seminal vesicles, prostate and bulbourethral glands, which produce ~99% of the seminal fluid and pour the same into the posterior urethra; and Vas or ductus deferens, which conducts spermatozoa from epididymis to urethra. Components that participate for expulsion include Pelvi-perineal striated muscles, with a major role for the bulbospongiosus muscle, which rhythmically contracts to powerfully propel sperm and semen from the posterior urethra to the urethral meatus. The contractions are under more or less voluntary control and occur at about 0.8 seconds interval. Considerable initial voluntary control of emission progressively decreases until the point of ejaculatory inevitability and Bladder neck sphincter, which intensely contracts to prevent sperm from flowing backward into the bladder (retrograde ejaculation).
Ejaculation is under the control of spinal ejaculatory generator (SEG) centre, located at L1-L2 level in lumbar spine. This centre receives sensory as well as parasympathetic and sympathetic inputs from the penile nerves and communicates via motor and autonomic nerves to thereby coordinate emission and ejaculation. The sympathetic as well as parasympathetic nerves innervate epididymis, vas deferens, seminal vesicle, prostate, bladder neck and urethra. They stimulate in a synchronized manner to cause pulsatile ejection of semen. Both sympathetic and parasympathetic neural supply stimulate semen secretion which is synchronized by sympathetic stimulated contraction of muscles of epididymis, ejaculatory ducts, seminal vesicles and prostate to propel its outflow into the urethra.
Ejaculation is strongly mingled with other sexual and behavioural responses (e.g., desire, motivation, erection, orgasm and even social relationships). In addition, the ejaculatory response being a short-lasting phenomenon there are rapid neurochemical changes in CNS. Dopamine and 5-HT receptors are involved in the ejaculatory process. Dopamine causes excitation of the ejaculatory neuroaxis whilst 5-HT is inhibitory. The speed of ejaculation is determined by a tilt in balance of 5-HT action on 5- HT2C and 5-HT1A receptors. Stimulation of 5-HT2C receptors delays ejaculation whereas agonism of 5-HT1A by 5-HT results in shorter ejaculation latency.
The sequence of events in the ejaculatory process is as follows: 5-HT is liberated from the neuronal terminals into the synaptic cleft. The liberated 5-HT binds with postsynaptic 5-HT receptors, namely, 5- HT1A, 5-HT2A & 5-HT2C. When 5-HT combines with postsynaptic 5-HT2C as well as 5-HT2A receptors, the ejection is delayed. The stimulation of postsynaptic 5-HT1A receptors mediates ejaculation. The Ejaculatory Latency Time (ELT) is the outcome of the action of 5-HT on postsynaptic 5-HT2C & 5-HT2A – delaying and 5-HT1A receptors – mediating ejaculation. The 5-HT in the synapse also combines with presynaptic 5-HT receptors, namely, 5-HT1A & 5-HT1B. 5-HT in synapse also stimulates the presynaptic 5-HT1B receptors which facilitate further release of 5-HT into the synapse as required. Besides postsynaptic 5-HT1A, 5-HT also combines with presynaptic 5- HT1A receptors to stop 5-HT release and thereby facilitate ejaculation. Depending on the ELT adequacy achieved by stimulating postsynaptic 5-HT receptors, 5-HT either combines more powerfully with either presynaptic receptors – 5HT1B to delay or 5-HTT to rapidly remove 5-HT from the synapse (and push it back into the pre-synaptic neuron). Following emission, the ejaculation process needs to be terminated by reducing 5-HT availability in the synapse. This is achieved by the synaptic 5-HT, following ejaculation, stimulating the inhibitory presynaptic 5-HT1A receptors. Activation of the 5-HT1A receptor has a proejaculatory effect; however, activation of the 5-HT1B, 5-HT2A and 5-HT2C receptors delays ejaculation.
Hyposensitivity of the 5-HT2C and/or hypersensitivity of the 5-HT1A receptors have been suggested as a possible explanation of lifelong PE. Men with low 5-HT neurotransmission and probable 5-HT2C receptor hyposensitivity may have their ejaculatory threshold genetically “set” at a lower point so as to ejaculate quickly, and with minimal stimulation.
Current interventions include pharmacologic therapy, surgical treatments (penile prosthesis), topical therapy, hormonal treatment, psychosocial interventions (behavioural interventions, cognitive behavioural therapy, hypnosis, and mindfulness-based interventions), and complementary and alternative medicine (CAM) treatments (such as physical activity yoga, herbals, nutraceuticals), with varying use and effectiveness.
Pharmacological treatment is the form of therapy most employed for premature ejaculation (Mohee A., Eardley I. Medical therapy for premature ejaculation. Ther. Adv. Urol. 2011. 3(5) 211-222). Lifelong PE is a genetically determined biological variable related to the inherited sensitivity of central 5-HT receptors. Moreover, traditional SSRIs (selective serotonin re-uptake inhibitors) were used off-label in the past for the treatment of PE following the observation that their use in the therapy of depression frequently caused, as a side effect, ejaculation delay (Waldinger MD. Premature ejaculation definition and drug treatment. Drugs 2007; 67(4): 547-568). It should be pointed out that no conventional SSRI is approved for therapy of PE. Their use therefore remains still today off-label (Waldinger MD, Zwinderman AH et al. Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: A systematic review and meta-analysis. Int J Impot Res. 2004. 16:369-81). SSRIs for PE include five drugs: citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline with a similar pharmacological mechanism of action. To date, dapoxetine is the sole drug approved for PE.
However, treatment with the above-indicated drugs, i.e. SSRIs and dapoxetine, is associated with a set of side effects, among which fatigue, drowsiness, postural hypotension, nausea, dizziness, anxiety, vomiting, diarrhoea, dry mouth, excessive perspiration, effects which cause a high rate of patients dropout (patients having poor compliance to the therapy (Mondaini N, Fusco F et al. Dapoxetine treatment in patients with lifelong premature ejaculation: the reason of a "Waterloo". Urology. 2013; 82(3):620-4).
Several authors have reported their experience with PDE-5 inhibitors in combination with SSRIs as a treatment for PE. However, the side effects of these agents is a challenge to their efficacious use especially since “ED-PE men had a significantly higher prevalence of hypertension, diabetes, and cardiovascular (CV) diseases. Hence, the drugs given must not only be effective but also safe. Concomitant intake of PDE-5i with SSRI can blunt the erectile process, but even potentially cause an ejaculation. Moreover, as PE and ED share a vicious cycle, it is paradoxical that where a man trying to control his ejaculation, he instinctively reduces his level of excitation (which can lead to ED); and a man trying to achieve an erection basically attempts to increase his excitation (which can lead to PE).
Thus, a need exists to provide effective treatment for PE and ED with higher efficacy and safety. Present inventors develop a nutraceutical composition which is a natural approach for PE especially with those experiencing concomitant ED. The present invention is safer than drug options available for ED & PE since it has well documented natural ingredients having synergistic effect for normalizing the sexual act in PE with or without associated ED.

Summary of the Invention
In order to solve the side effects associated with drugs for the treatment of PE, the present invention contain nutraceutical composition comprising L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 as active ingredients, on as-needed basis, on demand . It provides a nutraceutical composition for treating, preventing or improving male premature ejaculation, characterized in that taking.
In one general aspect, there is provided a nutraceutical composition comprising herbal active ingredients and essential vitamins in a patient comprising administering to said subject a solid or liquid oral nutraceutical composition wherein herbal active ingredients and essential vitamins selected from L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6, respectively.
In another general aspect there is provided a tablet or hard gelatin capsule or soft gelatin capsule composition comprising L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 for the treatment of Premature Ejaculation and Erectile dysfunction.

In another general aspect there is provided a powder composition comprising L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 for the treatment of Premature Ejaculation and Erectile dysfunction in a patient comprising administering to said subject.

In another general aspect there is provided a sachet dosage form comprising L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 for the treatment of Premature Ejaculation and Erectile dysfunction in a patient comprising administering to said subject which is easy to take.

Embodiments of the nutraceutical composition may include one or more of the following features. For example, the nutraceutical composition may further include one or more nutraceutically acceptable excipients. For solid oral dosage forms like tablets, capsules (hard gelatin and soft gelatin capsules), powders and sachets, the nutraceutically acceptable excipients may include one or more diluents, binders, disintegrants, glidants, lubricants, sweeteners/taste masking agents, compression aids, colorants and flavors and the like.

For liquid oral dosage forms like syrups or suspensions, the nutraceutically acceptable excipients may include one or more viscosity controlling agent, suspending agents, emulsifiers, solubilizers, buffers, sweeteners/taste masking agents, colorants and flavors and the like.

In still another aspect, there is provided a process for preparing a nutraceutical composition of herbal active ingredients including L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 comprising the steps of preparing a homogeneous mass by mixing herbal active ingredients with a suitable binder, milling the mass and sizing to obtain granules, blending the granules of active ingredients and one or more nutraceutically acceptable excipients; and filling into sachet dosage form or compressing the blend to obtain tablets.

In still another aspect, there is provided a process for preparing a nutraceutical composition of herbal active ingredients including L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 comprising the steps of preparing a homogeneous mass by mixing herbal active ingredients and a suitable binder, milling the mass and sizing to obtain granules, blending the granules of active ingredients and one or more nutraceutically acceptable excipients; and filling the blend to obtain capsules (both hard gelatin and soft gelatin capsules).

In still another aspect, there is provided a process for preparing a nutraceutical composition of herbal active ingredients including L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 comprising the steps of preparing a homogeneous mass by mixing herbal active ingredients and essential vitamins, and dispersing with a liquid and one or more nutraceutically acceptable excipients; and providing a dosage form in the form of syrup.

The details of one or more embodiments of the present invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description.

Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention can be modified in many different forms; the scope of the invention should not be construed as limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
Detailed Description of the Invention
The present invention will be described in detail below.
Where weight percentages are used they are based on total product weight unless otherwise is indicated.
The expression "Oral" as used herein refers to routes of administration through the gastrointestinal tract or lungs, and to formulations for use in administering drugs by such routes. The expression "Oral" as used herein includes, for example, enteral administration, which also includes Buccal, Sub-labial, Sublingual administration, routes and formulations. The words "Oral" and "enteral" are used interchangeably herein. The expression "Enteral Medications" as used herein includes various forms, which also includes Tablets, Capsules, Chewable capsules, Powders or Granules, Teas, Drops and Liquid medications or Syrups.
The solid oral nutraceutical composition of the present invention may be developed in the form of tablets, capsules, powders, pellets, granules, microspheres, mini tablets or any suitable solid unit dosage forms known to person skilled in the art; mouth dissolving tablets; dispersible tablets; effervescent tablets; trilayer tablets; in-lay tablets. The preferred dosage forms are tablets and capsules filled with pellets, granules or mini tablets as these are more convenient and easier to administer.
The term “tablet” comprises tablets without a coating and tablets with one or more coatings. Furthermore the “term” tablet comprises tablets having one, two, three or even more layers and press-coated tablets, wherein each of the before mentioned types of tablets may be without or with one or more coatings. The term “tablet” also comprises mini, melt, chewable, effervescent and orally disintegrating tablets.
A “nutraceutical dosage form” of the invention herein refers to a solid dosage form. The preferred solid dosage form is an oral dosage form. The most preferred solid dosage form is a sachet dosage form.
The sachet according to the invention may also be referred to as bag or infusion package or pouch or the like, all suitably referred to as “sachet” in the context of this invention. The term sachet includes powder or granules or pellets or microspheres or coated microspheres filled in a bag or pouch and the like.
This sachet may have any 3 dimensional forms such as round, square, rectangular, triangular.
The present invention relates to nutraceutical solid and liquid oral nutraceutical compositions of herbal active ingredients and essential vitamins for treating, preventing or improving male premature ejaculation.
The solid and liquid oral nutraceutical compositions comprising herbal active ingredients selected from L-arginine, Safed Musli, Grape seed extract, Myo-inositol, D-chiro-inositol, L-tryptophan and vitamin B6 a combination thereof.
The solid and liquid oral nutraceutical compositions comprising essential vitamins selected from vitamin B6 or a combination of other vitamins thereof.
The L-arginine used in the inventive oral nutraceutical composition are employed in an amount ranging from 50% to 60% w/w, preferably from 50% to 55% w/w and more preferably from 50% to 53 % w/w for solid oral composition.
The Safed musli (Chlorophytum borivilianum) used in the inventive oral nutraceutical composition are employed in an amount ranging from 30% to 40% w/w, preferably 30% to 35 % w/w and more preferably 30% to 32 % w/w for solid oral composition.
The Myo-Inositol used in the inventive oral nutraceutical composition are employed in an amount ranging from 10% to 20% w/w, preferably 10 to 15 % w/w and more preferably 10 to 12 % w/w for solid oral composition.
The L-tryptophan used in the inventive oral nutraceutical composition are employed in an amount ranging from 1% to 10% w/w, preferably to 2% to 5% w/w and more preferably 1 to 3 % w/w for solid oral composition.
The Grape seed extract used in the inventive oral nutraceutical composition are employed in an amount ranging from 1% to 10% w/w, preferably to 1% to 5% w/w and more preferably 1% to 2% w/w for solid oral composition.
The D-chiro-inositol used in the inventive oral nutraceutical composition are employed in an amount ranging from 0.1% to 1% w/w, preferably to 0.1% to 0.5% w/w and more preferably 0.25% to 0.5% w/w for solid oral composition.
The vitamin B6 used in the inventive oral nutraceutical composition are employed in an amount ranging from 0.01% to 0.05% w/w, preferably to 0.01% to 0.03% w/w and more preferably 0.01% to 0.02 % w/w for solid oral composition.
Nutraceutically acceptable excipients for use in the oral solid nutraceutical composition may comprise one or more diluents or bulking agents, binders, disintegrants, glidants, lubricants, sweeteners/taste masking agents, compression aids, colorants, preservatives and flavours or a combination thereof.
Suitable diluents or bulking agents which include, but are not limited to, saccharides, including monosaccharides, disaccharides, polysaccharides and sugar alcohols such as arabinose, lactose, dextrose, sucrose, fructose, maltose, mannitol, erythritol, sorbitol, xylitol, lactitol, and other bulking agents, such as powdered cellulose, microcrystalline cellulose, starch, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, dextrose, kaolin, magnesium carbonate, magnesium oxide, purified sugar and derivatives thereof.
Suitable binders, which include, but are not limited to, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carbomers, dextrin, ethyl cellulose, methylcellulose, shellac, zein, gelatin, polymethacrylates, polyvinyl pyrrolidone, starch, pregelatinized starch, polyvinyl alcohol, tragacanth, sodium alginate, gums, synthetic resins, silicic acid, hydrophilic polymers and the like.
The bulking agents or diluents used in the inventive oral nutraceutical composition are employed in an amount ranging from 50% to 60% w/w%, preferably from 50 to 55 w/w% and more preferably from 50 to 53 w/w% for solid oral composition.
Suitable disintegrants which include, but are not limited to, croscarmellose sodium, crospovidone, sodium starch glycolate, corn starch, potato starch, maize starch and modified starches like pregelatinized starch, calcium silicates, and low-substituted hydroxypropylcellulose.
Suitable lubricants and glidants which include, but are not limited to, talc, metallic stearates such as magnesium stearate, calcium stearate, zinc stearate; colloidal silicon dioxide, finely divided silicon dioxide, stearic acid, hydrogenated vegetable oil, glyceryl palmitostearate, glyceryl monostearate, glyceryl behenate, polyethylene glycols, powdered cellulose, starch, sodium stearyl fumarate, sodium benzoate, mineral oil, magnesium trisilicate, kaolin; and the like. It would be appreciated that a person skilled in the art is cognizant of the fact that lubricant, glidant or anti-tacking agent may be used interchangeably.
Suitable taste masking agents may include one or more of polymers, sweeteners and flavours. Most preferred polymers include one or more of cellulose acetate, polymethacrylates, hydroxyl propyl methyl cellulose, hydroxypropyl cellulose, hydroxylethyl cellulose; and the like.
Suitable sweeteners that may be used, comprises saccharides such as sucrose, dextrose, glucose, maltose, dextrins, D-tagatose, trehalose, dried invert sugar, fructose, levulose, galactose, sucralose 955, corn syrup solids, and the like, alone or in combination. Other examples of sweeteners comprise sodium saccharin; aspartame; sugarless sweeteners including polyhydric alcohols such as sorbitol, mannitol, xylitol, glycerol, hydrogenated starch hydrolysates, maltitol, isomaltitol, erythritol, lactitol and the like, alone or in combination.
Suitable flavours that may be used, comprise cinnamon, wintergreen, eucalyptus, spearmint, peppermint, menthol, anise as well as fruit flavours such as apple, pear, peach, strawberry, cherry, apricot, orange, watermelon, banana and the like; bean-derived flavors, such as coffee, cocoa and the like or mixtures thereof.
Suitable “surfactants” used for preparing a nutraceutical composition of Acetaminophen may include one or more of anionic, cationic, non-ionic or zwitter ionic surfactants or mixtures thereof.
Suitable cationic surfactants may include one or more of quaternary ammonium compounds, such as benzalkonium chloride, cetyl trimethyl ammonium bromide and dodecyl dimethyl ammonium bromide, hexadecyl (cetyl) trimethyl ammonium bromide, dodecyl pyridinium chloride, lauryl dimethyl benzyl ammonium chloride, acyl carnitine hydrochlorides, alkyl pyridinium halides and dodecylamine hydrochloride and the like.
Suitable anionic surfactants may include one or more of salts of aliphatic monoesters of sulfuric acid and soaps, such as potassium laurate; sodium dodecyl sulphate; alkyl polyoxyethylene sulfates; sodium alginates; sodium lauryl sulphate and sodium heptadecyl sulphate; sulfonated aromatic agents such as alkyl benzene sulfonic acids and salts thereof, such as tridecylbenzene sulphonic acid and the sodium and amino salts of dodecylbenzene sulphonic acid; alkyl naphthalene sulfonates, such as sodium butylnaphthalene sulphonate, sulphosuccinates such as sodium dioctyl sulphosuccinate and N-acyl-N-alkyl fatty acid taurates; sulfated polyoxyethylated alcohols; sulfated oils; dioctyl sodium sulfosuccinate, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl inosine, phosphatidylserine, phosphatidic acid and their salts, glyceryl esters, sodium carboxymethylcellulose, cholic acid and other bile acids (e.g., cholic acid, deoxycholic acid, glycocholic acid, taurocholic acid, glycodeoxycholic acid) and salts thereof and the like.
Suitable non-ionic surfactants may include one or more of polyoxyethylene fatty alcohol ethers (Macrogol and Brij), polyoxyethylene sorbitan fatty acid esters (Polysorbates), polyoxyethylene fatty acid esters (Myrj), sorbitan esters (Span), glycerol monostearate, polyethylene glycols, polypropylene glycols, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, aryl alkyl polyether alcohols, polyoxyethylene-polyoxypropylene copolymers (poloxomers), polaxamines, methylcellulose, hydroxycellulose, hydroxy propylcellulose, hydroxy propylmethylcellulose, noncrystalline cellulose, polyvinyl alcohol, and polyvinylpyrrolidone. In a preferred form of the invention the nonionic surfactant is a polyoxyethylene and polyoxypropylene copolymer and preferably a block copolymer of propylene glycol and ethylene glycol. Such polymers are sold under the tradename Poloxamer also sometimes referred to as Pluronic.
Suitable zwitter ionic surfactants may include one or more of alkyl betaines, alkyl amidopropyl betaines, alkyl sulphobetaines, alkyl glycinates, alkyl carboxyglycinates, alkyl amphopropionates, alkyl amidopropyl hydroxysultaines, acyl taurates and acyl glutamates wherein the alkyl and acyl groups have from 8 to 18 carbon atoms such as cocamidopropyl betaine, sodium cocoamphoacetate, cocamidopropyl hydroxysultaine, and sodium cocamphopropionate and the like.
The solid oral nutraceutical composition of the present invention can be manufactured by using various granulation techniques known to the person skilled in the art, but not limited to direct compression, wet granulation, dry granulation, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion, and solvent evaporation.
In an embodiment, the solid oral nutraceutical composition of the present invention may be prepared by granulating the admixture of herbal active ingredients and essential vitamins optionally with one or more nutraceutical excipients. The resulting granules may be compressed to form tablets or filled in hard gelatin or soft gelatin capsules. Alternatively, the process of manufacturing the solid oral nutraceutical composition of the present invention may comprise a step of granulating mixture of herbal active ingredients and essential vitamins with one or more nutraceutical excipients followed by complete or partial coating of the resulting granules with mixture of active ingredients. The coated granules may be compressed to form tablets or filled in hard gelatin or soft gelatin capsules.
In another embodiment, the solid oral nutraceutical composition of the present invention may be developed in the form of pellets, which can be prepared by coating one or more layers of mixture of herbal active ingredients and essential vitamins on non-pareil sugar seeds or inert core. The resulting pellets may be admixed with nutraceutical excipients and filled into hard gelatin capsules or soft gelatin capsules or may be compressed with nutraceutical excipients to form tablets.
Alternatively, the pellets can be prepared by completely or partially coating particles of the solid oral nutraceutical composition of the present invention. The resulting pellets may be admixed with nutraceutical excipients and filled into hard gelatin or soft gelatin capsules or may be compressed with nutraceutical excipients to form tablets.
The solid oral nutraceutical composition of the present invention may be seal coated. Preferably, the composition is seal coated and finally film coated. The composition can be coated with ready colour mix systems (such as opadry colour mix systems).
The components of the solid oral nutraceutical composition of the present invention defined hereinbefore can be brought together into a suitable composition for oral administration according to standard practice and procedures well known in the art of nutraceutical science using conventional formulation and manufacturing techniques.
Nutraceutically acceptable excipients for use in the oral liquid nutraceutical composition or a syrup composition may comprise an excipient such as a viscosity controlling agent, a sweetener, a suspending agent, an emulsifier, a pH controlling agent, a preservative, a colorant, a flavouring agent and a solvent.
Suitable preservatives which include, citric acid, sodium citrate but are not limited to and the like Benzoates, Sorbates including potassium sorbate, calcium sorbate and sodium sorbate, Propionates, Nitrites, Sulfites, including sodium sulfite, sodium bisulfite, sodium metabisulfite, potassium bisulfite and potassium metabisulfite and Vitamin E (tocopherol).
Suitable colorants which include, Titanium Dioxide, Iron Oxide Red, Iron Oxide Yellow, Iron Oxide Black (tocopherol)., Tartrazine, Annatto extract Dehydrated beets (beet powder) Caramel [beta]-Apo-8'-carotenal [beta]-Carotene Cochineal extract; carmine Toasted partially defatted cooked cottonseed flour Grape color extract, Paprika Paprika oleoresin Mica-based pearlescent pigments Riboflavin Saffron Tomato lycopene extract; tomato lycopene concentrate Turmeric Turmeric oleoresin, FD&C Blue # 2 (Indigo Carmine), FD&C Blue # 1 (Brilliant Blue), FD&C Yellow # 6 (Sunset Yellow).
The following examples are provided to enable one skilled in the art to practice the invention and are merely illustrative of the present invention. The examples should not be read as limiting the scope of the present invention.

EXAMPLES:
COMPOSITION
Each Sachet of Granules contains:
1 L-tryptophan 260 mg
2 Myo-Inositol 1.1 g
3 D-chiro-inositol 27.6 mg
4 Vitamin B6 2 mg
5 L-arginine 5 g
6 Grape seed extract 120 mg
7 Safed musli (Chlorophytum borivilianum) 3 g
Other ingredients: Sucralose (955), Citric acid (330), Starch, Polyethylene glycol (1521), Polyvinyl pyrrolidone (1201)
Colour: Tartrazine

Binder and the herbal Active ingredients were dissolved in suitable solvents therein by means of a high-shear homogenizer. The mixture was then wet granulated and the resultant moist, coherent, non-pasty granulate was screened through a 4-mesh sieve, and dried in a fluidized bed drier at a temperature of about 50°-60° C. until a moisture-content of less than 2% had been achieved. The resulting dried granules were re-screened through a 16-mesh sieve to eliminate agglomerates and further mixed with colorants, preservatives and sweeteners.
All citations are incorporated in their entirety by reference.