Compositions for supporting women with gynaecological syndromes

Abstract

The present invention relates to compositions for oral administration, suitable for supporting women with gyneacological syndromes, which comprise a) one or more inositol stereoisomers that contribute to the normal function of the ovaries, one of said inositol stereoisomers is necessarily myo-inositol, and when said composition also comprises D-chiro-inositol, the myo-inositol: D-chiro-inositol ratio ranges from 2:1 to 5:1, b) one or more vitamins, which are selected from one or more vitamins of the B complex, c) one or more additional active substances other than inositol stereoisomers and vitamins of the B complex, which are selected from one or more hormones involved in the normal function of the ovaries and / or one or more herbal extracts that contribute to the normal psychological function and / or one or more amino acids and d) one or more inactive excipients.

Description

[0001] Compositions for Supporting Women with Gynaecological Syndromes

[0002] Description of the Invention

[0003] The present invention relates to compositions for oral administration, suitable for supporting women with gyneacological syndromes, which comprise a) one or more inositol stereoisomers that contribute to the normal function of the ovaries, one of said inositol stereoisomers is necessarily myo-inositol, and when said composition also comprises D-chiro-inositol, the myo-inositol:D-chiro-inositol ratio ranges from 2:1 to 5:1, b) one or more vitamins, which are selected from one or more vitamins of the B complex, c) one or more additional active substances other than inositol stereoisomers and vitamins of the B complex, which are selected from one or more hormones involved in the normal function of the ovaries and / or one or more herbal extracts that contribute to the normal psychological function and / or one or more amino acids and d) one or more inactive excipients.

[0004] Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, with lifelong implications from adolescence to menopause, Moreover, another gynecological syndrome, the Premenstrual syndrome (PMS) includes clinically significant physical and psychological manifestations during the luteal phase of the menstrual cycle, leading to significant discomfort and reduced functional capacity. These symptoms disappear within a few days of the onset of menstrual flow. The cumulative prevalence of women of reproductive age who experience PMS worldwide is 47,8%. PMS symptoms include changes in appetite, weight gain, abdominal pain, headache, breast swelling and tenderness, anxiety, irritability, fatigue, worry, and mood swings.

[0005] Dysfunction in glucose metabolism and insulin resistance has been associated with PMS symptoms. Hormonal fluctuations creating estrogen dominance and progesterone deficiency are common models believed to lead to premenstrual syndrome symptoms. Another cause of PMS could be elevated prolactin levels, resulting in hormonal imbalance [Gudipally PR, Sharma GK. StatPearls Publishing; Treasure Island, FL: 2022, Premenstrual Syndrome]. The stereoisomers of inositol, myo-inositol and D-chiro-inositol are the two most abundant members of a family of nine stereoisomers and are widely found in nature. Inositols act as secondary messengers for insulin, and their deficiency contributes to the various features of both PCOS and PMS. Myo-inositol and D-chiro-inositol help regulate hormonal balance and improve insulin sensitivity, which may reduce symptoms such as mood swings and bloating. Moreover, they can reduce insulin resistance, improve ovarian function, and lower androgen levels in women with PCOS. Myo-inositol promotes glucose uptake and is also involved in pathways mediated by follicle-stimulating hormone (FSH), affecting the proliferation and maturation of follicular cells. Under the influence of insulin, myo-inositol is converted to D-chiro- inositol, which stimulates glycogen production and facilitates glucose uptake. Hyperinsulinemia in PCOS enhances the activity of ovarian epimerase, thereby increasing D-chiro-inositol synthesis. Myo-inositol is also thought to enhance aromatase synthesis in follicular cells, reducing androgen production [Singh S, Pal N, Shubham S, et al. Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics. J Clin Med. 2023, 12(4), 1454; Artini PG, Di Berardino OM, Papini F, et al. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013, 29, 375-9; Nestler JE, Vitorio U. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol. Endocrinol. 2015, 31(7), 501-5], Inositol is also involved in the progesterone pathway, whose levels are reduced in PMS [Martin BR, Woodruff J. Management of a Patient With Premenstrual Syndrome Using Acupuncture, Supplements, and Meditation: A Case Report. J Chiropr Med. 2023;22(3): 222-229].

[0006] Insulin resistance in women with PCOS is associated with elevated homocysteine (Hey). Furthermore, intensive PCOS treatment may affect homocysteine levels. Hyperhomocysteinemia is strongly linked to an increased risk of cardiovascular disorders, such as atherosclerosis, thrombosis, and dyslipidaemia. The role of vitamin B12 in remethylating homocysteine to methionine is well-established, and hyperhomocysteinemia is a hallmark of vitamin B12 deficiency. Plasma homocysteine is also a sensitive biomarker of folic acid deficiency, demonstrating folic acid's critical role in preventing homocysteine accumulation. Previous studies have shown that therapy with folic acid and vitamin B12 improves insulin resistance in patients with metabolic syndrome [Mahatjan P, Hong P. The Effects of Plasma Homocysteine in PCOS Women: A Review. Open Journal of Obstetrics and Gynecology, 2018, 8, 39-50; Liu Q et al. Vitamin B12 status in metformin treated patients: systematic review. PloS One 2014, 9(6), el00379; Kilicdag EB, Bagis T, Tarim E, et al. Administration of B- group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial. Hum. Reprod. 2005, 20(6), 1521- 8].

[0007] Folic acid (vitamin B9), riboflavin (vitamin B2), and cobalamin (vitamin B12) are involved in homocysteine metabolism. Moreover, in one study, supplementation with folic acid and inositol as monotherapies increased serum progesterone levels [Martin BR, Woodruff J. Management of a Patient With Premenstrual Syndrome Using Acupuncture, Supplements, and Meditation: A Case Report. J Chiropr Med. 2023;22(3):222-229],

[0008] Pyridoxine, also known as vitamin B6, has been clinically evaluated for its potential role in managing PMS symptoms. By improving serotonin and dopamine levels in the brain, pyridoxine is effective in relieving certain emotional symptoms of PMS, such as irritability, mood swings, depression, and anxiety. As pyridoxine plays a significant role in various physiological processes in the body, its supplementation is also associated with the Improvement of certain physical symptoms of premenstrual syndrome, such as reduced abdominal bloating, breast tenderness, and edema [Kashanian M, Mazinani R, Jalalmanesh S, Babayanzad Ahari S. Pyridoxine (vitamin B6) therapy for premenstrual syndrome. Int J Gynaecol Obstet. 2007;96:43-44].

[0009] Vitamins B2, B6, and B12 are vital for the formation of red blood cells, contributing to reduced fatigue and improved energy levels. They also support normal psychological function and the nervous system, helping to manage mood swings and irritability associated with PMS. Folic acid (vitamin B9), also called folate, supports normal immune system function and reduces fatigue, which may be particularly beneficial during the premenstrual phase.

[0010] Melatonin (N-acetyl-5-methoxytryptamine) is secreted by the pineal gland, Its rhythmic secretion regulates sleep, circadian rhythms, and immune responses. Melatonin is also a potent endogenous antioxidant, and supplementation has antioxidative and anti-inflammatory effects. Emerging evidence suggests meiatonin's involvement in ovarian physiology, including ovulation, follicular development, luteal function, and oocyte maturation. Melatonin deficiency appears to play a role in the pathophysiology of PCOS [Jamiiian M, Foroozanfard F, Mirhosseini N, et al. E^ffects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress

[0011] Parameters in Women With Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2019, 10, 273].

[0012] Chasteberry (Vitex Agnus Castus) extract is known for its ability to balance hormones, particularly by affecting prolactin levels. This may help relieve symptoms such as breast tenderness, irritability, and mood swings. It acts by regulating the levels of hormones involved in the menstrual cycle, particularly by increasing progesterone levels, acting on the hypothalamic-pituitary-gonadal axis to increase luteinizing hormone (LH) secretion, which in turn stimulates progesterone production [Shaw S, Wyatt K, Campbell J, Ernst E, Thompson-Coon J. Vitex agnus castus for premenstrual syndrome.

[0013] Cochrane Database Syst Rev. 2018;2018(3):CD004632],

[0014] Rooibos extract is rich in antioxidants, helps reduce oxidative stress and inflammation, and decreases free radicals in a dose-dependent manner with a profile similar to vitamins C and E, while low doses of green rooibos demonstrated significant anxiolytic effects in a zebrafish model, acting on GABA receptors, along with proven inhibition of MAO-A (monoamine oxidase A) [Lopez V, Casedas G, Petersen-Ross K, Powrie Y, Smith C. Neuroprotective and anxiolytic potential of green rooibos (Aspalathus linearis) polyphenolic extract. Food Funct. 2022; 13(l):91-101]. This calming effect may help with anxiety and stress, which are commonly present during premenstrual syndrome.

[0015] N~acetylcysteine (NAC) is a potent antioxidant, that helps reduce inflammation by lowering levels of pro-inflammatory cytokines and oxidative stress [Ding M, Soydemir OC. Efficacy of N-acetylcysteine In reducing inflammation and oxidative stress to prevent complex regional pain syndrome type 1. Medicine (Baltimore).

[0016] 2024;103(38):39742]. It also supports liver function, aiding in hormone detoxification and reducing PMS symptoms. Document EP3178474A1 describes soft gel capsule formulations comprising inositol and at least one of folic acid, cocoa polyphenols, genistein, L-arginine, vitamin E, selenium, N-acetylcysteine, and melatonin. However, this document does not specify the mandatory triple combination of inositol stereoisomers, vitamins, and hormones, nor does it detail the exact quantities of the components, as described in the present invention.

[0017] Document WO2019166984A1 describes a composition comprising myo-inositol and D- chiro-inositol for weight reduction, improvement of metabolic and hormonal parameters, and skin condition in women with PCOS. The myo-inositol to D-chiro- inositol weight ratio is 10:1 or lower, and the composition may include additional vitamins but does not mention the presence of hormones like melatonin or ratios of myo-inositol to D-chiro-inositol above 30:1, as described herein.

[0018] Document US2022072018A1 describes a composition comprising a protein and inositol, along with folic acid, However, it does not specify the mandatory triple combination of inositol stereoisomers, vitamins, and hormones, such as melatonin, as described in the present invention.

[0019] Document US2011159123A1 refers to a composition for relieving premenstrual syndrome, which contains approximately 5% to approximately 95% by weight of Tribulus terrestris extract and approximately 5% to approximately 95% by weight of one or more herbal extracts selected from white willow biological extract, chasteberry extract, mulberry extract, Ginkgo biloba extract, and various vitamins such as A, D3, and B family. However, it nowhere mentions the presence of the remaining components of the present invention. Document EP3375439A1 refers to a use of pinitol, D-chiro-inositol, or an analog thereof for the prevention, relief, or treatment of premenstrual syndrome. However, the said document does not mention combination with any of the components of the present invention.

[0020] Document US2007253941A1 refers to a preparation for treating the symptoms of premenstrual syndrome comprising at least two of the following components: y- linolenic acid, evening primrose oil, chasteberry extract, one or more B vitamins, folic acid, biotin, calcium, and magnesium, without however mentioning the presence of Rooibos extract or inositol derivatives, as in the present invention. Document EP3758798A1 refers to compositions comprising myo-inositol and D-chiro- inositol for use in methods of weight reduction, improvement of metabolic and hormonal parameters, and improvement of skin condition in women with PCOS, characterized in that the myo-inositoi and D-chiro-inositol have a weight ratio of 10:1 or lower, preferably 9:1. The said document does not mention a myo-inositoi :D-chiro- inositol weight ratio from 2:1 to 5:1, nor the mandatory presence of specific extracts, as in the present invention.

[0021] Thus, the prior art has not disclosed a composition suitable for supporting women with gyneacological syndromes, such as PCOS or PMS, which comprises: a) one or more inositol stereoisomers that contribute to the normal function of the ovaries, one of said inositol stereoisomers is necessarily myo-inositol, and when said composition also comprises D-chiro~inositol, the myo-inositol:D-chiro-inositol ratio ranges from 2:1 to 5:1, b) one or more vitamins, which are selected from one or more vitamins of the B complex, c) one or more additional active substances other than inositol stereoisomers and vitamins of the B complex, which are selected from one or more hormones involved in the normal function of the ovaries and / or one or more herbal extracts that contribute to the normal psychological function and / or one or more amino acids and d) one or more inactive excipients.

[0022] Given the challenges in managing gynaecological issues of hormonal origin and the emerging need for natural complementary' solutions to enhance therapeutic pharmaceutical treatment, the development of a safe complementary option is today an urgent clinical need to strengthen the management of symptoms in gynaecological syndromes as PCOS and PMS. Such an option would alleviate PCOS or PMS symptoms, improve the metabolic and hormonal profiles of affected women and alleviate side effects like mastalgia. For this reason, the use of active substances with a scientifically substantiated mechanism of action without adverse effects emerges as a real need in modern medicine. At the same time, it is considered necessary to focus on an easy- to-use pharmaceutical form for increased patient compliance, as well as to increase the shelf life of the product.

[0023] Despite the beneficial properties of the individually used components mentioned above, there is a demand for dietary supplements with even more pronounced supportive action in gynaecological syndromes as PCOS and PMS. Thus there is need of compositions that are suitable to simultaneously address many different issues such as insulin resistance, improve ovarian function, reduce androgen levels, promote glucose uptake, engage FSH-mediated pathways affecting follicular cell proliferation and maturation, stimulate glycogen production, facilitate glucose uptake, remethylate homocysteine to methionine (reducing hyperhomocysteinemia), and participate in ovarian physiology, including ovulation, follicular development, luteal function, and oocyte maturation, increase progesterone levels in serum, improve of serotonin and dopamine levels in the brain, improve the immune system function and reduce of fatigue, reduce of oxidative stress and inflammation, as well as anxiolytic effect and hormone detoxification.

[0024] The present invention was found after measurements to solve all the above problems of the prior art, and indeed with unexpectedly beter results regarding the alleviating of symptoms PCOS and PMS, the improvement of the metabolic and hormonal profile of these women, and the treatment of mastalgia.

[0025] Additionally, the invention offers the advantage of addressing PCOS while simultaneously reducing fatigue, improving nervous system function (due to the vitamins), and shortening sleep onset time (due to the hormones).

[0026] Furthermore, it presents the advantage of addressing premenstrual syndrome symptoms with simultaneous reduction of fatigue, improvement of normal nervous system function (due to the specific vitamins), as well as normal psychological function (due to the specific extracts). Indeed, the advantages are clearly better than compositions without the specific vitamins and / or without the specific extracts.

[0027] Moreover, the specific composition of the present invention, comprising a) one or more inositol stereoisomers that contribute to the normal function of the ovaries, one of said inositol stereoisomers is necessarily myo-inositol, and when said composition also comprises D-chiro-inositol, the myo-inositol :D-chiro-inositol ratio ranges from 2:1 to 5:1, b) one or more vitamins, which are selected from one or more vitamins of the B complex, c) one or more additional active substances other than inositol stereoisomers and vitamins of the B complex, which are selected from one or more hormones involved in the normal function of the ovaries and / or one or more herbal extracts that contribute to the normal psychological function and / or one or more amino acids and d) one or more inactive excipients, presents the unexpected advantage of even more pronounced effects compared to compositions comprising each component individually or some but not all of them.

[0028] Moreover, the chosen dosage forms of the present invention were found to increase the patient compliance and improve product stability.

[0029] More specifically, the present invention is defined by the following definitions:

[0030] Definition 1. Composition for oral administration, suitable for supporting women with gyneacological syndromes, which comprises a) one or more inositol stereoisomers that contribute to the normal function of the ovaries, one of said inositol stereoisomers is necessarily myo-inositol, and when said composition also comprises D-chiro-inositol, the myo-inositol :D-chiro-inositol ratio ranges from 2:1 to 5:1, b) one or more vitamins, which are selected from one or more vitamins of the B complex, c) one or more additional active substances other than inositol stereoisomers and vitamins of the B complex, which are selected from one or more hormones involved in the normal function of the ovaries and / or one or more herbal extracts that contribute to the normal psychological function and / or one or more amino acids and d) one or more inactive excipients.

[0031] Definition 2. Composition according to definition 1, which is formulated in orodispersible granules or tablets or granules for oral suspension or granules for direct ingestion or soft capsules, hard capsules or oral solutions or oral suspensions or singledose oral solution suitable for immediate consumption from the container (’’push and drink"), preferably as orodispersible granules or single-dose oral solution suitable for immediate consumption from the container, wherein said container consists of a vial and a storage cap that seals the vial, wherein said vial comprises the liquid phase in solution form and said cap comprises the solid phase and wherein the content ingredients can be mixed shortly before administration, by getting the solid phase into contact with the liquid phase by pressing the cap, and wherein after mixing, the cap is removed, aiiowing immediate consumption of the solution created in the vial.

[0032] Definition 3. Composition according to any one of definitions 1 to 2, wherein the amount of myo-inositol ranges from 500 to 2000 mg per formulation, preferably is 1000 mg per formulation or 1100 mg per formulation.

[0033] Definition 4. Composition according to any one of definitions 1 to 3, which comprises folic acid (vitamin B9) and vitamin B12 and wherein the amount of folic acid (B9) ranges from 0,1 to 0,6 mg per formulation, preferably is 0,2 mg or 0,3 mg per formulation and the amount of vitamin B12 ranges from 0,005 to 0,05 mg per formulation, preferably is 0,025 mg or 0,01 mg per formulation.

[0034] Definition 5. Composition according to definition 4, which further comprises vitamin B2 and vitamin B6 and wherein the amount of vitamin B2 ranges from 1,0 to 8,0 mg per formulation, preferably is 4,4 mg per formulation and the amount of vitamin B6 ranges from 1,0 to 8,0 mg per formulation, preferably is 4,2 mg per formulation.

[0035] Definition 6. Composition according to any one of definitions 1 to 5, wherein melatonin is selected as the hormone involved in the normal function of the ovaries and wherein the amount of melatonin ranges from 0,5 to 2 mg per formulation, preferably is 1 mg per formulation.

[0036] Definition 7. Composition according to any one of definitions 1 to 6, wherein the herbai extract contributing to normal psychological function is selected from Vitex Agnus Castus extract and / or Rooibos extract and wherein the amount of Vitex Agnus Castus extract ranges from 20 to 100 mg per formulation, preferably is 60 mg per formulation and the amount of Rooibos extract ranges from 20 to 120 mg per formulation, preferably is 60 mg per formulation. Definition 8. Composition according to any one of definitions 1 to ltwherein the amino acid selected is N-acetylcysteine and wherein the amount of N-acetylcysteine ranges from 20 to 200 mg per formulation, preferably is 100 mg per formulation. Definition 9. Composition according to any one of definitions 1 to 8, which may comprise an additional stereoisomer of inositol that contributes to the normal function of the ovaries and said stereoisomer of inositol is D-chiro-inositol, wherein the ratio of myo-inositol:D-chiro-inositol ranges from 2:1 to 5:1 and wherein the amount of D- chiro-inositol ranges from 250 to 500 mg per formulation, preferably is 291 mg per formulation.

[0037] Definition 10. Composition according to any one of definitions 1 to 9, which additionally comprises per formulation one or more excipients, selected from one or more diluents and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more preservatives and / or one or more pH adjusting agents and / or one or more solvents and / or one or more anti-caking agents and / or one or more lubricants.

[0038] Definition 11. Composition according to definition 10, wherein the diluent is preferably mannitol DC or isomalt, the flavor enhancer is preferably berry flavor or apricot flavor, the sweetener is preferably sucralose and / or sodium saccharin and / or neohesperidin dihydrochalcone and / or steviol glycosides, the preservative is preferably sodium benzoate and / or potassium sorbate, the pH adjusting agent Is preferably citric acid, the solvent Is preferably water and the lubricant is preferably PEG 6000. Definition 12. Composition according to any one of definitions 1 to 8 and 10 to 11, which comprises myo-inositol, folic acid, vitamin 812 and melatonin.

[0039] Definition 13. Composition according to definition 12, which comprises myo-inositol in an amount of 1000 mg per formulation, folic acid in an amount of 0,2 mg per formulation, vitamin B12 in an amount of 0,025 mg per formulation and melatonin in an amount of 1 mg per formulation. Definition 14, Composition according to definition 13, which is in the formulation of a single-dose oral solution suitable for immediate consumption from the container ("push and drink") comprising i) in the liquid phase into the vial, myo-inositol in the form of solution in an amount of 1000 mg per formulation and II) in the solid form into the vial cap, folic add in an amount of 0,2 mg per formulation, vitamin 812 in an amount of 0,025 mg per formulation and melatonin in an amount of 1 mg per formulation, said formulation is suitable for direct consumption from its container after mixing the solid and liquid forms.

[0040] Definition 15. Composition according to any one of definitions 1 to 11, which comprises myo-inositol, D-chiro-inositol, folic acid, vitamin B12, vitamin 82, vitamin 86, Vitex agnus-castus extract, Rooibos extract and N-acetylcysteine.

[0041] Definition 16. Composition according to definition 15, which is in the form of orodispersible granules and comprises myo-inositol in an amount of 1100 mg per formulation, D-chiro-inositol in an amount of 291 mg per formulation, folic acid in an amount of 0,3 mg per formulation, vitamin B2 in an amount of 4,4 mg per formulation, vitamin 86 in an amount of 4,2 mg per formulation, vitamin 812 in an amount of 0,01 mg per formulation, Vitex agnus-castus extract in an amount of 60 mg per formulation, Rooibos extract in an amount of 60 mg per formulation and N-acetylcysteine in an amount of 100 mg per formulation.

[0042] Definition 17. Dietary supplement comprising the composition according to any one of definitions 1 to 16.

[0043] The present invention solves previously unmet needs and problems of the prior art, delivering stronger support for alleviating PCOS symptoms and improving metabolic and hormonal profiles through reducing insulin resistance, improving ovarian function, decreasing androgen levels, enhancing glucose uptake, engagement in FSH-mediated pathways affecting follicular cell proliferation and maturation stimulating glycogen production, remethylating homocysteine to methionine that leads to reduce of hyperhomocysteinemia and participation in ovarian physiology, including ovulation, follicular development, luteal function, and oocyte maturation.

[0044] The present invention solves problems and needs not covered by the prior art and indeed with even more pronounced supportive action in the treatment of RMS with simultaneous actions in reducing insulin resistance, improving ovarian function, promoting glucose uptake, involvement in pathways mediated by follicle-stimulating hormone (FSH) that affect the proliferation and maturation of follicular cells, stimulation of glycogen production, remethylation of homocysteine to methionine leading to reduction of hyperhomocysteinemia, participation in ovarian physiology, increase in serum progesterone levels, improvement of serotonin and dopamine levels in the brain, improvement of immune system function and reduction of fatigue, reduction of oxidative stress and inflammation, anxiolytic effect, hormone detoxification and mitigation of mastalgia.

[0045] It was surprisingly found that the specific composition of the present invention, as defined by the above definitions, demonstrated the above effects more pronouncedly compared to compositions comprising each component individually or some but not all components without the exact combination.

[0046] Additionally, it was surprisingly found that the specific composition of the present invention, as defined by the above definitions, demonstrated synergy, compared to compositions comprising each component individually or some but not all components without the exact combination.

[0047] Furthermore, it was surprisingly found that the specific composition of the present invention as defined by the above definitions, demonstrated effective treatment of polycystic ovary syndrome with simultaneous reduction of fatigue, improvement of normal nervous system function, as well as concurrent reduction in sleep onset time. Additionally, it was surprisingly found that the specific composition of the present invention, as defined by the above definitions, demonstrated treatment of premenstrual syndrome with simultaneous reduction of fatigue, improvement of normal nervous system function, mitigation of mastalgia, as well as normal psychological function. Moreover, it was surprisingly found that the formulation in single-dose oral solution suitable for immediate consumption from the container (’’push and drink”) presented easier patient compliance, especially in patients with swallowing problems, as well as increased stability, as it maintains the active ingredients in separate compartments of the container, cap and vial, avoiding incompatibilities that create stability problems.

[0048] Finally, it was surprisingly found that the more is restricted the scope of the claims, the more intense are the effects and the advantages of the present invention.

[0049] The compositions of the present invention can be prepared by methods already known in the state of art.

[0050] The present invention is further described by the following indicative, but non-limiting examples. Example 1: In a preferred embodiment, the composition of the present invention comprises the following:

[0051] The composition of the present Example 1 is formulated as a single-dose oral solution suitable for immediate consumption from the container ("push and drink") of 10 mL, which consists of a vial and a storage cap that seals the vial. For administration, the cap is pressed with force until the powder falls into the solution, followed by shaking until complete dissolution of the powder. After mixing, the cap is removed, allowing immediate consumption of the solution created within the vial. Said formulation of "push and drink" increases the patient compliance and improves product stability.

[0052] One vial is administered daily before sleep or as advised by the doctor. The composition of the present Example 1 is suitable for supporting women with Polycystic ovary syndrome (PCOS).

[0053] The composition of the present Example 1 exhibits all the advantages of the present invention.

[0054] Example 2; In a preferred embodiment, the composition of the present invention comprises tine following:

[0055] The composition of the present Exampie 2 is formulated as o redispersible granules. Said formulation of orodispersibie granules increases the patient compliance and improves product stability.

[0056] The composition of the present Example 2 is suitable for supporting women with Premenstrual syndrome (PMS).

[0057] The composition of the present Example 2 presents all the advantages of the present Invention.

Claims

Claims1. Composition for oral administration, suitable for supporting women with gyneacological syndromes, which comprises a) one or more inositol stereoisomers that contribute to the normal function of the ovaries, one of said inositol stereoisomers is necessarily myo-inositol, and when said composition also comprises D-chiro-inositol, the myo-inositol: D-chiro-inositol ratio ranges from 2:1 to 5:1, b) one or more vitamins, which are selected from one or more vitamins of the B complex, c) one or more additional active substances other than inositol stereoisomers and vitamins of the B complex, which are selected from one or more hormones involved in the normal function of the ovaries and / or one or more herbal extracts that contribute to the normal psychological function and / or one or more amino acids and d) one or more inactive excipients.

2. Composition according to claim 1, which is formulated In orodisperslble granules or tablets or granules for oral suspension or granules for direct ingestion or soft capsules, hard capsules or oral solutions or oral suspensions or single-dose oral solution suitable for immediate consumption from the container (’’push and drink"), preferably as orodisperslble granules or single-dose oral solution suitable for immediate consumption from the container, wherein said container consists of a vial and a storage cap that seals the vial, wherein said vial comprises the liquid phase in solution form and said cap comprises the solid phase and wherein the content ingredients can be mixed shortly before administration, by getting the solid phase into contact with the liquid phase by pressing the cap, and wherein after mixing, the cap is removed, allowing immediate consumption of the solution created in the vial.

3. Composition according to any one of claims 1 to 2, wherein the amount of myoinositol ranges from 500 to 2000 mg per formulation, preferably is 1000 mg per formulation or 1100 mg per formulation.

4. Composition according to any one of claims 1 to 3, which comprises folic add (vitamin B9) and vitamin B12 and wherein the amount of folic add (B9) ranges from 0,1 to 0,6 mg per formulation, preferably is 0,2 mg or 0,3 mg per formulation and the amount of vitamin B12 ranges from 0,005 to 0,05 mg per formulation, preferably is 0,025 mg or 0,01 mg per formulation.

5. Composition according to claim 4, which further comprises vitamin B2 and vitamin B6 and wherein the amount of vitamin B2 ranges from 1,0 to 8,0 mg per formulation, preferably is 4,4 mg per formulation and the amount of vitamin B6 ranges from 1,0 to 8,0 mg per formulation, preferably is 4,2 mg per formulation.

6. Composition according to any one of claims 1 to 5, wherein melatonin is selected as the hormone involved in the normal function of the ovaries and wherein the amount of melatonin ranges from 0,5 to 2 mg per formulation, preferably is 1 mg per formulation.

7. Composition according to any one of claims 1 to 6, wherein the herbal extract contributing to normal psychological function is selected from Vitex Agnus Castus extract and / or Rooibos extract and wherein the amount of Vitex Agnus Castus extract ranges from 20 to 100 mg per formulation, preferably is 60 mg per formulation and the amount of Rooibos extract ranges from 20 to 120 mg per formulation, preferably is 60 mg per formulation.

8. Composition according to any one of claims 1 to 7, wherein the amino add selected is N-acetylcysteine and wherein the amount of N-acetylcysteine ranges from 20 to 200 mg per formulation, preferably is 100 mg per formulation.

9. Composition according to any one of claims 1 to 8, which may comprise an additional stereoisomer of inositol that contributes to the normal function of the ovaries and said stereoisomer of inositol is D-chiro-inositol, wherein the ratio of myo-inositol: D-chiro-inositol ranges from 2:1 to 5:1 and wherein the amount of D-chiro-inositoi ranges from 250 to 500 mg per formulation, preferably is 291 mg per formulation.

10. Composition according to any one of claims 1 to 9, which additionally comprises per formulation one or more excipients, selected from one or more diluents and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more preservatives and / or one or more pH adjusting agents and / or one or more solvents and / or one or more anti-caking agents and / or one or more lubricants.

11. Composition according to claim 10, wherein the diluent is preferably mannitol DC or isomalt, the flavor enhancer is preferably berry flavor or apricot flavor, the sweetener is preferably sucralose and / or sodium saccharin and / or neohesperidin dihydrochalcone and / or steviol glycosides, the preservative is preferably sodium benzoate and / or potassium sorbate, the pH adjusting agent is preferably citric acid, the solvent is preferably water and the lubricant is preferably PEG 6000.12, Composition according to any one of claims 1 to 8 and 10 to 11, which comprises myo-inositol, folic acid, vitamin B12 and melatonin.

13. Composition according to claim 12, which comprises myo-inositol in an amount of1000 mg per formulation, folic acid in an amount of 0,2 mg per formulation, vitamin B.12 in an amount of 0,025 mg per formulation and melatonin in an amount of 1 mg per formulation.

14. Composition according to claim 13, which is in the formulation of a single-dose oral solution suitable for immediate consumption from the container ("push and drink") comprising i) in the liquid phase into the vial, myo-inositol in the form of solution in an amount of 1000 mg per formulation and ii) in the solid form into the vial cap, folic acid in an amount of 0,2 mg per formulation, vitamin B12 in an amount of 0,025 mg per formulation and melatonin in an amount of 1 mg per formulation, said formulation issuitable for direct consumption from its container after mixing the solid and liquid forms.

15. Composition according to any one of claims 1 to 11, which comprises myo-inositol, D-chiro-inositol, folic acid, vitamin B12, vitamin B2, vitamin B6, Vitex agnus-castus extract, Rooibos extract and N-acetylcysteine.

16. Composition according to claim 15, which is in the form of orodispersible granules and comprises myo-inositol in an amount of 1100 mg per formulation, D-chiro-inositol in an amount of 291 mg per formulation, folic acid in an amount of 0,3 mg per formulation, vitamin B2 in an amount of 4,4 mg per formulation, vitamin B6 in an amount of 4,2 mg per formulation, vitamin B12 in an amount of 0,01 mg per formulation, Vitex agnus-castus extract in an amount of 60 mg per formulation, Rooibos extract in an amount, of 60 mg per formulation and N-acetylcysteine in an amount of 100 mg per formulation.

17. Dietary supplement comprising the composition according to any one of claims 1 to 16.