DESC: FORM 2

The Patents Act, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(Section 10, Rule 13)

ORAL COMPOSITION COMPRISING OF INOSITOLS AND ANTIOXIDANT

Dr. Reddy's Laboratories Ltd.
An Indian Company having its registered office at 8-2-337, Road No. 3, Banjara Hills, Hyderabad - 500034, Telangana, India

The following specification particularly describes the invention and the manner in which it is to be performed.

ORAL COMPOSITION COMPRISING OF INOSITOLS AND ANTIOXIDANT
FIELD OF THE APPLICATION
[0001] The present application relates to a nutraceutical composition comprising inositols and antioxidants. The application further relates to a nutraceutical composition comprising inositols, antioxidant(s) and micronutrients for use in alleviating the symptoms associated with Polycystic Ovarian Syndrome (PCOS) or Polycystic Ovarian Disease (PCOD).
BACKGROUND
[0002] PCOS is a multifactorial disorder affecting women of reproductive age. The polycystic ovary denotes the plurality of cysts (fluid-filled sacs) that form in the ovaries containing immature eggs (follicles). PCOS is characterized by menstrual abnormalities, including irregular menstrual cycle (periods), hyperinsulinemia, hyperandrogenism, multiple abnormal cysts, and enlarged ovaries. It may be further accompanied by symptoms like hirsutism (i.e. abnormal hair growth of facial hair and heavy hair growth on the arms, chest, and abdomen), acne, obesity, darkening of the skin, etc.
[0003] Women with PCOS present an adverse reproductive profile and potential risk of developing Type 2 diabetes and cardiovascular diseases (such as hypertension, dyslipidemia, etc.) pertaining to the endocrine and metabolic complications associated with the same. PCOS is also associated with psychological risk factors, including mood disorders such as depression and anxiety.
[0004] Inositol is a carbocyclic sugar found abundantly in the human body tissues that mediates cell signal transduction to hormones, neurotransmitters, and growth factors. Chemically, Inositol is a six-carbon polyol with the same molecular formula as glucose, and predominantly occurs in nine stereoisomeric forms, including Myo-inositol (MI) and D-chiro-inositol (DCI). Inositols are incorporated into cell membranes as phosphatidyl-MI, which is a precursor of inositol triphosphate (InsP3). InsP3 is a second messenger for many hormones, including insulin and follicle-stimulating hormone (FSH). Defects in tissue availability or altered metabolism of inositol have been shown to cause impaired insulin signaling and can lead to insulin resistance.
[0005] In the human body, Myo-inositol (MI) is found to induce estrogen production, while D-Chiro-inositol (DCI) has a role in the synthesis of androgens. Thus, an appropriate concentration of MI is required to ensure healthy oocyte maturation in the ovary. The enzyme epimerase (stimulated by insulin) converts MI to DCI, maintaining a physiological balance between the two.
[0006] Hyperinsulinaemia i.e. elevated insulin levels associated with PCOS alter the physiological MI-DCI balance.
[0007] Insulin resistance is a pathological condition in which a cell, tissue, or organism requires above-normal quantities of insulin to respond normally. Women with PCOS are observed to have insulin resistance leading to compensatory hyperinsulinemia. As mentioned earlier, hyperinsulinemia associated with PCOS alters the physiological MI-DCI balance, leading to hyperandrogenism.
[0008] Elevated levels of androgens may have a negative impact on follicular development. Hyperinsulinemia alters the FSH (Follicle Stimulating Hormone) to LH (luteinizing hormone) shift, preventing the selection of a dominant follicle. In healthy women, the ratio between LH and FSH usually lies between 1 and 2, but in women having PCOS, this ratio becomes reversed, and it might reach as high as 2 or 3.
[0009] In a nutshell, hormonal imbalance in PCOS adversely affects follicular development and mature oocyte formation, which further can lead to infertility.
[0010] Currently available compositions intended to be used as health supplements contain MI and DCI forms of inositol, mainly as tablets and capsules.
TECHNICAL PROBLEM
[0011] PCOS is a disorder involving various metabolic, endocrine, genetic, and environmental factors; and involves multi-pronged therapy or treatment options. The drugs used to address hyperinsulinemia may ameliorate the metabolic and reproductive PCOS features, however their side effects often lead to poor compliance. Further, the alongside prescribed medications for PCOS may alter the reproductive plans and choices that a woman might have.
[0012] Moreover, studies have shown that subjects suffering from PCOS are often at risk of micronutrient deficiencies. Usually deficiencies of some common minerals like potassium and magnesium and vitamins like B12 and B9 have been observed in subjects with PCOS. The deficiency of Vitamin D is also linked with PCOS, depression and insulin resistance.
[0013] Hence there is a need to develop a composition that can help in managing the hormonal imbalance responsible for most of the PCOS symptoms, and also provide essential micronutrients in order to address the deficit of micronutrients in PCOS subjects. The ideal composition would be the one that can be administered irrespective of the reproductive plans and variable health conditions of the user and the one which can easily fit in subjects daily dietary routine.
[0014] Further, there is a need of a composition that is easy-to-ingest, conveniently dosed and has acceptable organoleptic properties. None of the currently available products for addressing the symptoms of PCOS, can be added to any food, meal or beverage in a subject’s daily diet without hampering the original taste of the food, meal or beverage.
[0015] Moreover, in available products, there is no such product which can serve both as a standalone supplement and also as an adjunct to the subject’s daily food which can ultimately useful to alleviate the symptoms associated with PCOS.
[0016] The composition of the present application thus aims to provide a composition comprising the ingredients that alleviates the symptoms associated with PCOS, along with providing necessary micronutrients, and can either be used as a standalone supplement or as an adjunct to the foods or beverages that will aid to improve the reproductive health of the subjects suffering from PCOS.
SUMMARY OF THE APPLICATION
[0017] The present application aims to provide an oral composition that comprises a combination of ingredients that can help in restoring the hormonal balance and thereby alleviate the symptoms of PCOS and simultaneously supplies essential micronutrients to the body, which in turn improves the overall health of the user. In that respect, in one aspect the present application provides a nutraceutical composition that contains right amount of essential micronutrients, in addition to the components addressing the symptoms of PCOS; in a single formulation.
[0018] Another aspect of the present application is to provide a nutraceutical composition comprising inositols, antioxidants and micronutrients that can help to improve reproductive health and address micronutrient deficiencies in a subject.
[0019] In yet another aspect, the present application provides an oral nutraceutical composition that comprises a mixture of inositols and alpha-lipoic acid (ALA) along with essential micronutrients having positive effects on the health of patients suffering from PCOS.
[0020] In yet another aspect, the present application provides an oral nutraceutical composition which comprises of a mixture of inositols and antioxidant(s) along with essential micronutrients in an easy-to-carry, easy-to-consume, unit dose form that is formulated as powder, granules, pellets etc. which can either be used as a standalone supplement or as an adjunct to the foods or beverages that the subject usually consumes.
[0021] In an aspect of above embodiment, present application provides an oral nutraceutical composition comprising a mixture of inositols, antioxidant(s) and essential micronutrients, as an adjunct to the foods or beverages that the subject usually consumes wherein the nutraceutical composition does not hamper with the original taste of the foodstuff or beverage to which it is added to or sprinkled over.
[0022] The various embodiments herein disclose oral nutraceutical composition as described in the above mentioned objectives and the process of preparation for the same.
[0023] Other objects and advantages of the present application will become apparent to those skilled in the art upon reading the following detailed description of the preferred embodiments.
DETAILED DESCRIPTION OF THE APPLICATION
[0024] The present application relates to a composition that is a novel blend of active ingredients that can ameliorate PCOS symptoms; fortified with crucial micronutrients, that have been observed to have positive health outcomes for a subject suffering from PCOS.
[0025] As described above, there are multiple prongs to a PCOS treatment pertaining to the diversity of symptoms associated with it. Restoration of the balance between MI and DCI is one of the approaches used to alleviate the symptoms related to PCOS.
[0026] The present application relates to a composition comprising inositols and antioxidant(s), as a nutritional supplement. In a further aspect, the composition comprises micronutrients, including, but not limited to, vitamin D, vitamin B9, selenium, chromium, zinc etc., which are crucial in ameliorating the symptoms associated with PCOS and also address micronutrient deficiencies in the PCOS subjects.
[0027] The details of one or more embodiments of the present invention are outlined in this application. Modifications to embodiments described in this document and other embodiments will be evident to those of ordinary skill in the art after studying the information provided in this application. The information in this application, particularly the specific details of the described exemplary embodiments, is provided primarily for clear understanding, and no unnecessary limitations are to be understood therefrom.
[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art.
[0029] Definitions: The terms as used herein have the following meanings:
[0030] The term “comprising” is “open-ended” and means the elements recited, or their equivalent in structure or function, plus any other elements that are not recited. The terms “having” and “including” are also to be construed as open-ended unless the context suggests otherwise. These terms are not in the exclusive sense of “consisting only of.” All ranges recited herein include the endpoints, including those that recite a range “between” two values.
[0031] The terms “a” and “the” as used herein are understood to encompass the plural as well as the singular or otherwise clearly mentioned wherever needed. For example, “an excipient” includes one or more of such excipients.
[0032] As used herein, “about” and “up to” are understood to refer to numbers in a range of numerals. Moreover, all numerical ranges herein should be understood to include all integers, wholes, or fractions within the range.
[0033] As used herein, the term “at least” refers to the presence of the recited substance in the composition in recited least amount.
[0034] The terms “excipient(s)” or “additive(s)” are used interchangeably to mention any safe food acceptable material or a component of the composition that is not having any pharmacological effect, which is acceptable for use in nutritional compositions and does not provide any therapeutic effect, and may contribute to physicochemical properties or any relevant nontherapeutic function of the composition. The excipients that are useful in preparing a nutritional composition are generally safe, non-toxic, do not interact with other components of a composition in a harmful manner, and are acceptable for human or veterinary use. As used in the specification, the term “excipient” includes both one and more than one such excipient.
[0035] Non-limiting examples of excipients are flavours, anti-caking agents, adsorbents, disintegrants, glidants, diluents, adsorbents, lubricants, pharmaceutically acceptable carriers, preservatives, anti-oxidants, stabilizers, sweeteners and texturizers.
[0036] The terms “composition” and “formulation” are used interchangeably and refer to a mixture of two or more components, elements, or fractions. Also, the terms “composition” and “formulation” may refer to a mixture of the components with or without excipients/other carriers. The nutritional compositions in the present application are selected from but are not limited to bulk powders, powder in sachet form for a single use, microparticles, nanoparticles, powder for reconstitution, dispersion, suspension, emulsion forming compositions, tablets, chewable tablets and capsules.
[0037] The term “effective amount” is an amount that prevents a deficiency, treats a disease or medical condition in an individual, or, more generally, reduces symptoms, manages the progression of the disease, or provides a nutritional, physiological, or medical benefit to the individual.
[0038] While the terms “subjects,” “individual,” “user” and “patient” are used herein to refer to human females.
[0039] The term “powder” means and includes the product containing a dry, solid substance comprising of finely divided active pharmaceutical or nutraceutical or nutritional ingredient(s) with or without suitable excipient(s).
[0040] “Nutritional compositions” or “Nutritional preparations” or “Nutraceutical preparation” or “Nutraceutical composition” as used herein, are understood to include one or more of the dietary nutrients as components and any number of additional optional ingredients, including but are not limited to conventional food additives, health benefit additives, ingredients used to alleviate the symptoms or health issues associated with a particular disease/disorder, one or more, acidity regulators, bulking agents, thickening/gelling agents, buffers or agents for pH adjustment, chelating agents, colorants, flavorants, emulsifiers, mineral osmotic agents, pharmaceutically acceptable carriers, preservatives, antioxidants, stabilizers, sweeteners, texturizers. The optional ingredients can be added in any suitable amount. “Nutritional composition” further means a substance or composition that helps to address at least some of the nutritional deficiencies in the subject’s daily diet.
[0041] The term “adjunct” as used herein means and donotes the composition which can be added to or spinkled over any food or meal or beverage that the subject usually consumes as a part of her daily diet.
[0042] The term “PCOS” means Polycystic Ovarian Syndrome, which is a multifactorial disorder with various genetic, metabolic, endocrine, and environmental abnormalities mainly affecting the female reproductive system occurring in women of reproductive age. It is characterized by reproductive dysfunction, hyperandrogenism, anovulation, menstrual irregularity, infertility, and pregnancy complications and has a potential risk of developing Type 2 diabetes and cardiovascular diseases.
[0043] The terms PCOD (Polycystic Ovarian Disease) and PCOS (Polycystic Ovarian Syndrome) are often used synonymously, although there is a slight difference between the two. In case of PCOD, the ovaries start releasing immature eggs that lead to hormonal imbalances and swollen ovaries. In case of PCOS, multiple endocrine issues cause the ovaries to produce excess androgens, making eggs prone to becoming cysts that may not be released, like in PCOD, rather, they build up in the ovaries themselves. Pertaining to hormonal irregularities, PCOS is considered to be more complicated than PCOD. For the purpose of this application, the term PCOS (Polycystic Ovarian Syndrome) includes PCOD (Polycystic Ovarian Disease) as well.
[0044] As per the present application, the terms “to manage” or “managing” means and includes, but not limited to, “to alter”, or “to reduce” or “ to improve” or, to bring in desired change etc.
[0045] The term “micronutrients” as used herein, is to refer the foods or the compounds which are essential compounds needed in smaller amounts for biochemical processes such as the modulation of gene transcription, catalyzing enzymatic reactions, and protection against oxidative stress. These include vitamins, minerals, and antioxidants.
[0046] The term “vitamin” includes, but are not limited to any of various fat-soluble or water-soluble organic substances essential in minute amounts for normal growth and activity of the body and obtained naturally from plants and animal foods or synthetically made, pro-vitamins, derivatives, analogs, and the like or combinations thereof.
[0047] Non-limiting examples of vitamins include, but are not limited to, vitamin A, vitamin B1(thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin or niacinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride), vitamin B7 (biotin), vitamin B9 (folic acid), and vitamin B12 (various cobalamins; commonly cyanocobalamin in vitamin supplements), vitamin C, vitamin D, vitamin E, vitamin K, and the like or combinations thereof.
[0048] “Vitamin Premix” is a mixture containing two or more of the vitamins with or without any additional excipient(s). For example, it may comprise ingredients that include, but are not limited to, retinyl acetate, cholecalciferol, D-alpha tocopheryl acetate, pyridoxine hydrochloride, folic acid, cyanocobalamin, L-ascorbic acid, and the like or combinations thereof.
[0049] The term “mineral” includes but are not limited to, one or more minerals selected from sodium, boron, calcium, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, zinc, and the like or combinations thereof.
[0050] “Mineral Premix” is the mixture containing two or more of the minerals with or without any additional excipient(s). For example, it may comprise ingredients that include, but are not limited to, Zinc Sulphate monohydrate, Ferric sodium di-phosphate, Sodium Selenite, and the like or combinations thereof.
[0051] The term “antioxidant” includes, but is not limited to, any one or more of various substances such as beta-carotene (a vitamin A precursor), vitamin C, vitamin E, alpha-lipoic acid, and the like or combinations thereof, that inhibit oxidation or reactions promoted by reactive oxygen species (“ROS”) and other radical and non-radical species. Additionally, antioxidants are molecules capable of slowing or preventing the oxidation of other molecules.
[0052] Non-limiting examples of antioxidants include, but are not limited to, carotenoids, Ascorbyl Palmitate, coenzyme Q10 (“CoQ10”), flavonoids, glutathione Goji (wolfberry), hesperidin, lactowolfberry, lignan, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, zeaxanthin, alpha-lipoic acid, and the like or combinations thereof.
[0053] The term “inositol” comprises a set of compounds that are six-carbon polyols (cyclohexane-1,2,3,4,5,6-hexyl). Inositols are carbocyclic sugars found in various human body tissues, including the kidney, brain, liver, etc., participating in signal transduction of various hormones, neurotransmitters, and growth factors. Inositols are incorporated into cell membranes as phosphatidyl-MI, which is a precursor of inositol triphosphate (InsP3). InsP3 is a second messenger for many hormones, including insulin and follicle-stimulating hormone (FSH). Inositol can be converted into nine different stereoisomers by epimerization of its hydroxyl groups, among which MI and DCI are widely found in nature. Epimerase is an enzyme responsible for the physiological conversion of MI into DCI. Defects in tissue availability or altered metabolism of inositols have been observed in PCOS.
[0054] Non-limiting examples of sources of inositol include, but are not limited to, whole wheat bread, prunes, almonds, red kidney beans, peanut butter, and the like or combinations thereof.
[0055] Alpha-lipoic acid (ALA) (also known as 1,2-dithiolane-3-pentanoic acid or thioctic acid) is a caprylic acid-derived organosulphur compound that plays an essential role as a cofactor, assisting in the enzymatic nutrient breakdown. ALA is found in vegetables like spinach, broccoli, tomato, brussels sprouts and rice bran etc. and can be synthesized by enzymatic reactions in mitochondria as well. It is used to manage and treat chronic diseases associated with oxidative stress, such as diabetic neuropathy, and slow down the onset of metabolic syndrome by acting as an antioxidant.
[0056] ALA has poor water solubility and it is not stable under thermal process. Hence, it is a challenge to incorporate this compound in products such as oral solutions or water-dispersible powders. Further ALA has unpleasant intense odour and pungent taste which makes it difficult to consume.
[0057] Encapsulation is technique, by which drugs having solubility issues, palatability issues and environment sensitivity are enclosed within a desired inert material to achieve better better solubility, better palatability and better stability when exposed to environmental factors like light, temperature and others. Encapsulation of drugs is a vital strategy for poorly soluble, fragile or bitter tasting compounds and can achieve a stronger therapeutic effect along with minimized side effects. The terms “encapsulation” and “coating” are used synonymously in the present application.
[0058] Non-limiting examples of encapsulation techniques are one or more of inclusion complexes, spray drying, electrospraying, solid lipid nanoparticles (SLN), emulsification, and liposomes and combinations thereof.
[0059] Different compounds are used to encapsulate ALA which is to be incorporated into various formulations. Non-limiting examples of encapsulating agents or materials used to encapsulate ALA include one or more of chitosan, cyclodextrins, alginic acid, soy phosphatidylcholine, egg lecithin, cholesterol, Tween 20 , Tween 60 Tween 80, poly ethylene oxide, gelatin, HPMC, povidone, colloidal silicon dioxide, calcium caseinate, sodium alginate, phytosterol ester of linseed oil, ß-sitosterol, poloxamer 188, coconut oil, jojoba oil and macadamia oil and combinations thereof.
[0060] Present application makes use of encapsulated ALA in the nutraceutical formulations to modify its chemical and biological properties and improve its palatability, solubility and stability in the aqueous medium.
[0061] The term “coated ALA” as used herein means the ALA coated with appropriate encapsulating agent (s) using suitable encapsulation technique(s) known to a person skilled in the art. In the present application, the terms “coated ALA” and “encapsulated ALA” are used interchangeably.
[0062] Some minerals, which are essential micronutrients for the human body, also have an important role in addressing the symptoms of PCOS. Chromium is a vital micronutrient for glucose and insulin homeostasis. Chromium supplementation has been shown to have beneficial effects on decreasing BMI, fasting insulin, and free testosterone in PCOS patients. Further, Selenium is an essential micronutrient that can regulate hormonal profile by improving insulin metabolism and attenuating dyslipidemia. Further, selenium also helps in lowering oxidative and inflammatory indices. Zinc has positive effect on insulin resistance. It also helps to achieve lipid balance, hormonal balance and lowers hirsutism.
[0063] Unless otherwise stated, the abbreviations used in the present application have following meanings.
Abbreviation Full form/ meaning
MI Myo-Inositol
DCI D-Chiro Inositol
ALA Alpha-lipoic acid
PCOS Polycystic Ovarian/Ovary Syndrome
PCOD Polycystic Ovarian/Ovary Disease
CFU Colony Forming Units
[0064] The present application relates to a unique composition that combines carefully chosen ingredients along with essential dietary micronutrients, which can exert a positive synergistic effect on the health of subjects suffering from PCOS.
[0065] The present application relates to a nutraceutical composition for oral use which contains a novel blend of ingredients that are compatible with each other. It relates to a unique combination of ingredients alleviating the symptoms associated with PCOS and essential micronutrients, including selenium and chromium which have a role in reducing the symptoms of PCOS as well.
[0066] The present application relates to a unique combination of actives that combines the health benefits of essential micronutrients and natural ingredients addressing the symptoms associated with PCOS to achieve a synergistic positive effect on the female reproductive health in general, thus minimizing the need to take multiple nutritional supplements for addressing different issues associated with PCOS or PCOD.
[0067] The nutraceutical composition disclosed in the present application covers powder, granules, pellets and such other formulations, which can be prepared by spray drying, dry blending of the ingredients or such other process. These formulations have a much greater shelf life and can be readily consumed. The powdered or granules formulations can be packaged in various containers, including those for bulk provision, or a single serving. The composition can be reconstituted with water or other suitable fluids as required and be used for oral administration. Further the compositions can also be used as adjunct to the foods or beverages in the subject’s daily diet.
[0068] As mentioned above, an imbalance in the levels of inositols is one of the major factors leading to PCOS. The present application relates to a composition comprising of inositols and antioxidants, fortified with micronutrients, wherein the components of the composition are found to improve the reproductive health of the subject synergistically.
[0069] In some embodiments, the nutraceutical composition of the present application comprises effective amounts of: (i) MI and DCI (ii) ALA, and (iii) one or more micronutrients comprising of vitamins and minerals; wherein said composition has ability to improve overall reproductive health of a subject suffering from PCOS.
[0070] In yet another embodiment, the nutraceutical composition of the present application comprises effective amounts of: (i) MI and DCI (ii) ALA, and (iii) one or more micronutrients comprising of vitamins and minerals; wherein said composition improves the insulin sensitivity and helps to restore the hormonal balance in a subject suffering from PCOS.
[0071] In yet another embodiment, the nutraceutical composition of the present application comprises effective amounts of: (i) MI and DCI (ii) ALA, and (iii) one or more micronutrients comprising of vitamins and minerals; wherein said composition improves the regularity of the subject’s menstrual cycle.
[0072] Additionally, in some embodiments, the nutraceutical composition of the present application comprises effective amounts of: (i) MI and DCI (ii) ALA, and (iii) one or more micronutrients comprising of vitamins and minerals; wherein said composition improves the success rate of fertility of the subject.
[0073] In one embodiment, the nutraceutical composition of the present application comprises effective amounts of: (i) MI and DCI (ii) ALA, and (iii) one or more micronutrients comprising of vitamins and minerals; wherein said composition helps to address micronutrient deficiencies in a subject suffering from PCOS.
[0074] In an embodiment, the nutraceutical composition of the present application comprises inositol(s) or combinations thereof.
[0075] In an embodiment, the nutraceutical composition of the present application comprises inositol(s) in an amount of about 10% to 95% w/w of the composition.
[0076] In an embodiment, the nutraceutical composition of the present application comprises inositol(s) in an amount of about 20% to 85% w/w of the composition.
[0077] In an embodiment, the nutraceutical composition of the present application comprises inositol(s) in an amount of about 30% to 75% w/w of the composition.
[0078] In an embodiment, the nutraceutical composition of the present application comprises inositol(s) in an amount of about 40% to 65% w/w of the composition.
[0079] In an embodiment, the nutraceutical composition of the present application comprises inositol(s) in an amount of about 50% to 55% w/w of the composition.
[0080] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol and D-chiro inositol.
[0081] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol in an amount of about 15% to 85% w/w of the composition.
[0082] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol in an amount of about 25% to 75% w/w of the composition.
[0083] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol in an amount of about 35% to 65% w/w of the composition.
[0084] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol in an amount of about 45% to 55% w/w of the composition.
[0085] In an embodiment, the nutraceutical composition of the present application comprises D-chiro-inositol in an amount of about 0.1% to 10% w/w of the composition.
[0086] In an embodiment, the nutraceutical composition of the present application comprises D-chiro-inositol in an amount of about 0.1% to 5% w/w of the composition.
[0087] In an embodiment, the nutraceutical composition of the present application comprises D-chiro-inositol in an amount of about 0.5% to 3% w/w of the composition.
[0088] In an embodiment, the nutraceutical composition of the present application comprises D-chiro-inositol in an amount of about 1% to 2% w/w of the composition.
[0089] In an embodiment, the nutraceutical composition of the present application comprises inositols in an amount of 40 g to 90 g per 100 g of the composition.
[0090] In an embodiment, the nutraceutical composition of the present application comprises inositols in an amount of 50 g to 80 g per 100 g of the composition.
[0091] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol in an amount of 45 g to 90 g per 100 g of the composition.
[0092] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol in an amount of 50 g to 80 g per 100 g of the composition.
[0093] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol and D-chiro inositol in a ratio of 10:1 to 70:1.
[0094] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol and D-chiro inositol in a ratio of 20:1 to 60:1
[0095] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol and D-chiro inositol in a ratio of 30:1 to 50:1
[0096] In an embodiment, the nutraceutical composition of the present application comprises Myo-inositol and D-chiro inositol in a ratio of 40:1 to 45:1
[0097] In some embodiments, the nutraceutical composition of the present application provides about 1000 mg to about 4000 mg of inositol(s) per serving. In another embodiment, the nutraceutical composition provides about 2000 mg to about 3000 mg of inositol(s) per serving. In yet another embodiment, the nutraceutical composition provides about 2000 mg to about 2500 mg of inositol(s) per serving.
[0098] In some embodiments, inositol(s) may be added to the nutraceutical composition of the present application, at a concentration sufficient to deliver a target of about 1500 mg to 4000 mg of inositol(s) per day to the subject. The nutraceutical composition may be administered in one or more doses in a day to the subject, to reach the target/ required amount of inositol(s).
[0099] In an embodiment, the nutraceutical composition of the present application further comprises antioxidants.
[0100] In an aspect of above embodiment, antioxidants can be selected from, but are not limited to, carotenoids, ascorbyl palmitate, coenzyme Q10 (“CoQ10”), flavonoids, glutathione Goji (wolfberry), hesperidin, lactowolfberry, lignan, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, zeaxanthin, alpha-lipoic acid (ALA) or combinations thereof.
[0101] In an embodiment, the nutraceutical composition of the present application further comprises alpha-lipoic acid (ALA).
[0102] ALA has poor water solubility and it is not stable under thermal process. Hence, it is a challenge to incorporate this compound in products such as oral solutions or water-dispersible powders. Further ALA has unpleasant intense odour and pungent taste which makes it organoleptically less compliant.
[0103] In an embodiment, present application makes use of encapsulated ALA i.e. ALA encapsulated with suitable encapsulating agent; for better oxidative and thermal stability, better organoleptic properties, enhanced water solubility; which further may lead to better bioavailability.
[0104] In an embodiment, the nutraceutical composition of the present application comprises ALA wherein ALA is encapsulated/ coated with encapsulating agent selected from one or more of chitosan, cyclodextrins, alginic acid, soy phosphatidylcholine, egg lecithin, cholesterol, Tween 20, Tween 60 Tween 80, poly ethylene oxide, gelatin, HPMC, povidone, colloidal silicon dioxide, calcium caseinate, sodium alginate and combinations thereof.
[0105] In an embodiment, the nutraceutical composition of the present application comprises ALA coated with suitable encapsulating agent wherein ALA is present in the amount of 20% w/w to 95% w/w of the coated ALA.
[0106] In an embodiment, the nutraceutical composition of the present application comprises ALA coated with suitable encapsulating agent wherein ALA is present in the amount of 25% w/w to 90% w/w of the coated ALA.
[0107] In an embodiment, the nutraceutical composition of the present application comprises ALA coated with suitable encapsulating agent wherein ALA is present in the amount of 30% w/w to 85% w/w of the coated ALA.
[0108] In an embodiment, the nutraceutical composition of the present application comprises ALA coated with suitable encapsulating agent wherein ALA is present in the amount of 40% w/w to 80% w/w of the coated ALA.
[0109] In an embodiment, the nutraceutical composition of the present application comprises ALA coated with suitable encapsulating agent wherein ALA is present in the amount of 50% w/w to 70% w/w of the coated ALA.
[0110] In an embodiment, the nutraceutical composition of the present application comprises coated ALA in an amount of about 5% w/w to 40% w/w of the composition.
[0111] In an embodiment, the nutraceutical composition of the present application comprises coated ALA in an amount of about 10% w/w to 35% w/w of the composition.
[0112] In an embodiment, the nutraceutical composition of the present application comprises coated ALA in an amount of about 15% w/w to 30% w/w of the composition.
[0113] In an embodiment, the nutraceutical composition of the present application comprises coated ALA in an amount of about 20% w/w to 25% w/w of the composition.
[0114] In an embodiment, the nutraceutical composition of the present application comprises ALA in an amount of 2 g to 25 g per 100 g of the composition.
[0115] In an embodiment, the nutraceutical composition of the present application comprises ALA in an amount of 4 g to 20 g per 100 g of the composition.
[0116] In an embodiment, the nutraceutical composition of the present application comprises ALA in an amount of 6 g to 15 g per 100 g of the composition.
[0117] In an embodiment, the nutraceutical composition of the present application is sufficient to deliver a target of about 75 mg to 750 mg of ALA per day to a subject. The nutraceutical composition may be administered in multiple doses in a day to the subject, to reach the target/ required amount of ALA.
[0118] In an embodiment, the nutraceutical composition of the present application further comprises micronutrient portion comprising one or more vitamins, minerals, and additives.
[0119] In an embodiment, the nutraceutical composition of the present application comprises one or more vitamins selected from vitamin A (retinol), vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 (folic acid), vitamin B12 (cyanocobalamin), vitamin C (ascorbic acid), vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), vitamin E (alpha-tocopherol), vitamin K etc., and the like or combinations thereof.
[0120] In an embodiment, the nutraceutical composition of the present application comprises one or more minerals selected from boron, calcium, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, zinc etc., and the like or combinations thereof.
[0121] In an embodiment, the nutraceutical composition of the present application comprises zinc in an amount of about 50 mg to about 150 mg per 100g of the composition.
[0122] In an embodiment, the nutraceutical composition of the present application is sufficient to deliver a target of about 2 mg to 15 mg of zinc per day to a subject. The nutraceutical composition may be administered in multiple doses in a day to the subject, to reach the target/ required amount of zinc.
[0123] In an embodiment, the nutraceutical composition of the present application comprises selenium in an amount of about 250 µg to about 1200 µg per 100g of the composition.
[0124] In an embodiment, the nutraceutical composition of the present application is sufficient to deliver a target of about 10µg to 70 µg of selenium per day to a subject. The nutraceutical composition may be administered in multiple doses in a day to the subject, to reach a target/ required amount of selenium.
[0125] In an embodiment, the nutraceutical composition of the present application comprises chromium in an amount of about 250 µg to about 1200 µg per 100g of the composition.
[0126] In an embodiment, the nutraceutical composition of the present application is sufficient to deliver a target of about 10µg to 50µg of chromium per day to a subject. The nutraceutical composition may be administered in multiple doses in a day to the subject, to reach a target/ required amount of chromium.
[0127] In an embodiment, the nutraceutical composition of the present application comprises a micronutrient portion which comprises a vitamin premix and a mineral premix comprising one or more vitamins and one or more minerals, respectively.
[0128] In an embodiment, the nutraceutical composition of the present application comprises a micronutrient portion comprising of a vitamin premix and mineral premix in a ratio of 1:6 to 6:1
[0129] In an embodiment, the nutraceutical composition of the present application comprises a micronutrient portion comprising of a vitamin premix and mineral premix in a ratio of 1:4 to 4:1
[0130] In an embodiment, the nutraceutical composition of the present application comprises a micronutrient portion comprising of a vitamin premix and mineral premix in a ratio of 1:2 to 2:1
[0131] In an embodiment, the nutraceutical composition of the present application comprises micronutrients and inositols in the ratio of 1:10 to 1:30.
[0132] In an embodiment, the nutraceutical composition of the present application comprises micronutrients and inositols in the ratio of 1:15 to 1:25.
[0133] In an embodiment, the nutraceutical composition of the present application comprises micronutrients and inositols in the ratio of 1:18 to 1:22.
[0134] In an embodiment, the nutraceutical composition of the present application comprises micronutrients and coated ALA in the ratio of 1:1 to 1:10.
[0135] In an embodiment, the nutraceutical composition of the present application comprises micronutrients and coated ALA in the ratio of 1:3 to 1:8.
[0136] In an embodiment, the nutraceutical composition of the present application comprises micronutrients and coated ALA in the ratio of 1:5 to 1:6.
[0137] In an embodiment, the nutraceutical composition of the present application comprises coated ALA and inositols in the ratio of 1:1 to 1:10.
[0138] In an embodiment, the nutraceutical composition of the present application comprises coated ALA and inositols in the ratio of 1:3 to 1:8.
[0139] In an embodiment, the nutraceutical composition of the present application comprises coated ALA and inositols in the ratio of 1:5 to 1:6.
[0140] In an embodiment, the nutraceutical composition of the present application has no added sugar.
[0141] In an embodiment, the nutraceutical composition of the present application is meant for oral administration.
[0142] In another aspect of the present application, the oral nutraceutical composition can be formulated as powder, granules, pellets, minitablets, sachet, tablets, chewable tablets or capsules for suitable oral consumption.
[0143] In an embodiment, the nutraceutical composition of the present application may be consumed in an amount of 2 g to 10 g per day.
[0144] In an embodiment, the nutraceutical composition provides an energy between 10 kcal to 40 kcal per serve.
[0145] In another embodiment the application relates to the process of preparation of the nutraceutical composition.
[0146] In an embodiment, the application relates to the process for the preparation of the nutraceutical composition comprising, ingredients alleviating the symptoms associated with PCOS and essential micronutrients, including selenium , chromium.and zinc.
[0147] In another aspect of the above embodiments, the application relates to a process of preparation of the nutraceutical composition in the form of powder/granules comprising the steps of:
a) weighing, and mixing the ingredients comprising of one or more inositols and antioxidants;
b) adding and blending essential micronutrients comprising one or more vitamins and minerals, essentially including selenium and chromium to the mixture obtained in step (a).
[0148] In an aspect of the above embodiments, the application further relates to a process of preparation of the oral nutraceutical powder/granules composition.
[0149] In an aspect of the above embodiments, the application relates to a process of preparation of the nutraceutical composition in the form of powder/granules comprising dry blending of inositol, and ALA with micronutrient portion.
[0150] In an embodiment, the nutraceutical composition of the present application can be added to or sprinkled over any food, meal or drink in the subject’s daily diet.
[0151] According to one or more embodiments herein, the powder/granules prepared by one or more processes known in the art, including the teachings of the present application, can be further used in various products/ preparations including, but are not limited to, oral preparations like health supplements, fitness supplements, vitamin/ mineral formulas/ multivitamin preparations, smoothies, fruit juices, powdered drinks, breakfast cereals, cereal bars, ice creams, yogurts, dairy products, and the like or combinations thereof.
[0152] In an embodiment of the present application, the composition of the present application can be subjected to physicochemical tests and methods of evaluation including, but not limited to, particle size, particle shape, surface area, density (bulk density, true density, and granular density), granule strength, friability, flow properties (angle of repose, Hausner ratio, % compressibility index), moisture content, % fines, and dissolution etc. in order to ensure its physicochemical properties and bioavailability. Further, necessary modifications can be made to the compositions and process by the person skilled in the art in order to comply with the necessary standards with respect to the pharmacokinetic parameters.
[0153] In an embodment, the flow properties of the composition of the present invention are assessed using Hausner ratio and Carr’s index and such other tests. The flow properties are of the composition are categorized as follows:
Carr’s Index Flow Properties Hausner ratio
?10 Excellent 1.00-1.11
11-15 Good 1.12-1.18
16-20 Fair 1.19-1.25
21-25 Passable 1.26-1.34
26-31 Poor 1.35-1.45
32-37 Very poor 1.46-1.59
?38 Very very poor ?1.60
[0154] In an embodiment, the composition of the present application has Hausner ratio in the range of 1.00 to 1.30.
[0155] In an embodiment, the composition of the present application has Hausner ratio in the range of 1.00 to 1.25.
[0156] In an embodiment, the composition of the present application has Hausner ratio in the range of 1.00 to 1.15.
[0157] In an embodiment, the composition of the present application has Carr’s index in the range of 2.00 to 18.00.
[0158] In an embodiment, the composition of the present application has Carr’s index in the range of 4.00 to 15.00.
[0159] In an embodiment, the composition of the present application has Carr’s index in the range of 8.00 to 12.00.
[0160] In an embodiment, the composition of the present application has bulk density in the range of 0.1 to 1.0 g/mL.
[0161] In an embodiment, the composition of the present application has bulk density in the range of 0.3 to 0.8 g/mL.
[0162] In an embodiment, the composition of the present application has tapped density in the range of 0.1 to 1.0 g/mL.
[0163] In an embodiment, the composition of the present application has tapped density in the range of 0.3 to 0.8 g/mL.
[0164] In an embodiment, the composition of the present application has moisture content in the range of 1% to 12 %.
[0165] In an embodiment, the composition of the present application has moisture content in the range of 2% to 10%.
[0166] In an embodiment, the composition of the present application has moisture content in the range of 4% to 8%.
[0167] In an embodiment, the composition of the present application has particle size (d90) in the range of 250 microns to 1000 microns.
[0168] In an embodiment, the composition of the present application has particle size (d90) in the range of 400 microns to 750 microns.
[0169] In an embodiment, the composition of the present application has particle size (d90) in the range of 450 microns to 700 microns.
[0170] In an embodiment, the composition of the present application has particle size (d90) in the range of 500 microns to 650 microns.
[0171] In another embodiment, the composition of the present application is stable for a period of at least 12 months when subjected to stability testing under 25ºC/ 60% RH.
[0172] In another embodiment, the composition of the present application is stable for a period of at least 12 months when subjected to stability testing under 30ºC/ 65% RH.
[0173] In another embodiment, the composition of the present application is stable for a period of at least 12 months when subjected to stability testing under 40ºC/ 75% RH.
[0174] The present application is further illustrated by the examples provided merely to be exemplary of the nutraceutical composition described above and do not limit the scope of the application. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present application.
[0175] The present invention is illustrated below by reference to the following examples. However, the one skilled in the art will appreciate that the specific methods and results discussed are merely illustrative of the present invention and not to be construed as limiting the application. The following examples may include compilations of data that are representative of data gathered at various times during development and experimentation related to the present invention.
[0176] Different compositions are prepared as given in the tables below.
[0177] Examples 1- 7: Compositions comprising inositols, antioxidants and micronutrients
Some compositions contain coated ALA whereas some compositions contain non-coated ALA. Examples of combinations are given below in Table 1.
Table 1: Exemplary compositions comprising micronutrients, inositols and antioxidants
Sr. No. Ingredient Composition (% w/w)
Example 1 Example 2 Example 3 Example 4 Example 5
1. Coated ALA 12 15 18 24 -
2. Non-coated ALA 12 - - - 24
3. Myo-inositol 40 50 60 80 80
4. D-Chiro-inositol 1.5 1.5 1.5 1.5 1.5
5. Vitamin Premix 0.2 0.3 0.5 0.9 0.9
6. Mineral Premix 1.0 1.8 2.5 3.6 3.6
7. Excipients q.s. q.s. q.s. q.s. q.s.
Manufacturing process for above powder compositions:
The composition of the present application is prepared by a process comprising of the following steps:
Step I: Weigh and dispense all the materials including coated ALA and non-coated ALA in appropriate quantities and sift through suitable sieve;
Step II: Prepare a blend of vitamin premix, mineral premix and excipients;
Step III: Prepare a blend of MI and DCI
Step IV: Dry blend coated ALA or non-coated ALA with the blends mentioned in steps II and III.
Step V: Pack the powder composition prepared in the Step IV in a suitable container.
[0178] Experimental details: Evaluation of compositions.
Example 1, 3, 4 and 5 were subjected to organoleptic evaluation and other qualititative analysis tests. Results of this evaluation are as summarized in Table 2 below:
I. Evaluation for organoleptic parameters
Table 2: Evaluation of compositions for organoleptic parameters
Test Example 1 Example 3 Example 4 Example 5
Appearance White to off white free flowing powder White to off white free flowing powder White to off white free flowing powder White to off white free flowing powder
Odour Pungent odour Slight aroma Slight aroma Strong pungent odour
Taste Moderate pungeny on base of tongue Palatable and mild sweet taste. Very mild sweetness Burning sensation in throat and unpleasant after taste.
After taste Unpleasant after taste in mouth. No after taste. Slight pungent after taste Burning sensation in throat and unpleasant after taste.
Moisture content (%) 2.24 1.57 1.41 2.33
The compositions comprising of coated ALA had better palatability, and showed no discomfort or after taste. Hence, the compsotions with coated ALA were subjected to further tests and evaluation.
II. Results of stability studies
Example 3 was subjected to stability studies at room temperature (under 25ºC/ 60% RH) and accelerated conditions (under 40ºC/ 75% RH). Also, the compsotion was subjected to organoleptic and sensorial evaluation throughout the 6 months period. Results of stability studies are as summarized in Table 3 below:
Table 3:
Parameter Unit Specification Control 6 months - 25ºC/ 60% RH 6 months-
40ºC/ 75% RH
MI g/100g NLT 50 55.23 53.85 53.1
ALA mg/100g NLT 5506 6118 5883.29 4457.87
Moisture g/100g NMT 5% 1.57 1.53 1.47
Total plate count CFU/g 1x104 -1x105 - 130 480
Yeast and mould CFU/g 1x102 -1x103 - <10 <10
Enterobacteriaceae CFU/g 1x102 -1x103 - <10 <10
Salmonella CFU/g Absent/25g - Absent Absent
Listeria CFU/g Absent/25g - Absent Absent
The composition of example 3, comprising the coated ALA was found to comply with standard specifications and when subjected to sensorial evaluation tests throughout the 6 months, was unexpectedly found to retain superior sensorial qualities even with increased amount of ALA.
As an overall conclusion throughout the 6 months real time and 6 months accelerated shelf-life study of the composition, there was decrease in pungency observed in the product when compared against the reference & was found to be compliant with the standard sensory specification.
,CLAIMS:CLAIMS
We claim,
1. An oral composition for alleviating the symptoms associated with PCOS comprising,
i) one or more inositols;
ii) one or more antioxidants;
iii) micronutrients;
and nutraceutically acceptable excipients.
2. The composition as claimed in claim 1, wherein inositols are selected from Myo-inositol, D-chiro-inositol or combination thereof.

3. The composition as claimed in claim 1, wherein the antioxidants are selected from vitamin C, vitamin E, lipoic acid, alpha-lipoic acid, beta-carotene, and carotenoids or combinations thereof.

4. The composition as claimed in claim 3, wherein the antioxidant is encapsulated or non-encpasulated alpha-lipoic acid.

5. The composition as claimed in claim 1, wherein micronutrients are selected from vitamins, minerals and combinations thereof.

6. The composition as claimed in claim 1, wherein the composition comprises inositols in an amount of 40% w/w to 65% w/w and coated ALA in an amount of 10% w/w to 35% w/w of the total weight of the composition.

7. The composition as claimed in claim 1, wherein micronutrients and inositols are present in the ratio of 1:10 to 1:30.

8. The composition as claimed in claim 1, wherein micronutrients and antioxidants are present in the ratio of 1:1 to 1:10.

9. The composition as claimed in claim 1, wherein antioxidants and inositols are present in the ratio of 1:1 to 1:10.

10. The composition as claimed in claim 1, wherein said composition exhibits a Hausner ratio from 1.00 to 1.30 and Carr’s index from 2.00 to 18.00.

11. The process of preparation of composition as claimed in claim 1 comprising:
a) preparing a blend of inositiols, coated ALA with one or more excipients;
b) preparing a blend of essential micronutrients with one or more excipients;
c) dry mixing the blends in obtained in step (a) and step (b)
d) filling the powder composition prepared in the step (c) in a suitable packaging.