PHARMACEUTICAL OR NUTRACEUTIC COMPOSITION FOR THE PREVENTION AND / OR TREATMENT OF URO-GYNECOLOGICAL DISORDERS

Description

Our Ref.: I0207545 Description of the industrial invention entitled: “Pharmaceutical or nutraceutical composition for the prevention and / or treatment of uro- gynecological” By: ERBOZETA SPA, nationality of the Republic of San Marino, Strada delle Seriole 41 / 43, 47894 Chiesanuova, Republic of San Marino Designated inventors: Chiara PASTORELLI, Roberto ZA- MONEY ORDERS. Filed on: June 28, 2024 * * * DESCRIPTION Field of invention The present invention relates to a composition pharmaceutical or nutraceutical for prevention and / or the treatment of uro-gynecological disorders, in a particular pharmaceutical or nutritional composition ceutical, in the form of dosage units for administration oral extraction, including collagen peptides, astragalus powder, gotu kola extract- ca, mononucleotides, hyaluronic acid, for the pre- the treatment and / or the diagnosis of uro- gynecological. State of the art Urogynecology is a branch of gynecology which focuses on diagnosis and treatment problems related to the urinary and genital systems the feminine. This specialization deals mainly with mainly urinary incontinence and prolapse female genitalia, providing solutions for improving to improve the quality of life of patients. The pro- uro-gynecological problems can manifest themselves with a series of symptoms, among the most common are the in- urinary continence, the sensation of heaviness at the level the genitals, urinary and fecal retention, and the difficulty in sexual intercourse. Uro- gynecological therefore represent a broad category of conditions, among the main uro- gynecological ones include: genitourinary syndrome ria, vulvovaginal atrophy, lichen sclerosus atrophic, vulvovaginal itching and dryness vulvovaginal. Among these, genitourinary syndrome naria, when it appears in association with menopause you know, it's called genitourinary syndrome menopause (GSM, from the English “Genitourinary Syndro- me of Menopause”). This term includes a wide range of clinical manifestations, attribu- susceptible to estrogen deficiency, which affects the uro-gynecological tract of postmenopausal women break. In addition to menopause, other conditions also can cause the onset of GSM, among these cancer treatment is mentioned, therapy with radiation, chemotherapy and endocrine therapies adjuvants such as tamoxifen and inhibitors of aromatase. Previously known as aromatase atrophy vulvovaginal (VVA), GSM is a condition ca- characterized by a variety of symptoms including, a exemplary but not exhaustive title, dryness vaginal, burning, itching, irritation, dyspareun- nia and vaginal discharge. It may also be accompanied gnated by urinary signs and symptoms such as dysuria, in- urinary continence and frequent urinary tract infections urinary. This disorder also compromises, significantly the quality of life, health sexual and general well-being of people with pite. As women's life expectancy continues to continues to increase worldwide, it is expected that In developed countries, women will live longer than 30 years beyond natural menopause, which is usually occurs between the ages of 48 and 52. This prolonged postmenopausal period results in a greater likelihood of women experiencing symptoms of GSM. In fact, affecting up to 50% of the women who can be defined as “middle-aged” and elderly, the symptoms uro-gynecological micro-organisms related to menopause are cro- nici, progressive and unlikely to improve over time, presenting a significant concern bad for women's health in the 20s postmenopause. Despite its prevalence and the its impact, GSM remains an underdiagnosed disorder. neglected and poorly treated. About 70% of the women who experience these symptoms are not addressed to the doctor, often perceiving these manifestations as a natural aspect of menopause. Furthermore, 75% of patients presenting clinical signs of GSM doubts that their healthcare workers possess sufficient knowledge of the treatments available able to effectively address these problems. To date, the treatment of GSM requires a multifaceted approach, involving collaboration communication between the patient and different professionals specialists, including gynecologists, urologists, physio- therapists and psychologists: in fact, the treatment options treatment may include patient education you, lifestyle changes, treatments physical, non-hormonal therapies and, in some cases, hormonal treatments and receptor modulators hormonal. Adopting a sequential approach, as highlighted by Palacios et al. [Palacios S, Nappi RE, Cancelo MJ, Sánchez S, Simoncini T. Ex- pert opinion on the treatment of vulvovaginal atro- phy with ospemifene based on new evidence. Climac- teric. 2023 Aug;26(4):388–91], is advantageous for preserve vaginal health, mitigate signs and symptoms and improve the quality and sexual health of the lives of postmenopausal women. Given the chronic nature of GSM, a therapeutic intervention early and continuous is important to slow down the progression and prevent recurrence of symptoms. However, the challenge of ensuring adherence to treat- treatments, especially those applied via vaginal which typically see low persistence among patients, requires a treatment plan sequential and tailored. This strategy promotes the interchangeability of treatments over time, al- in line with the needs and preferences of the individual patients. In the field of non-hormonal therapies they are topical vaginal firming products have been suggested without a prescription, such as gels and creams. All- go on, it is important to note how these treatments are often not well received by patients, in addition to cause serious alterations to the vaginal ecosystem- which can lead to erosion of the mucosa, to increased vaginal discharge and a rate higher number of infections. Another example of therapy is the treatments aimed at restoring metabolism and functions connective tissue. Among these the most important many are the biostimulation that activates the functions anabolic properties of fibroblasts, particularly enhancing stimulate the production of collagen, elastin and acid type III hyaluronic acid from their precursors. via, few studies support the application of que- this treatment as a therapeutic strategy and, for as far as we know, none of them support a oral administration for vulvovaginal health during the GSM. There is therefore a need to explore re therapeutic alternatives aimed at amplifying and extend the effectiveness of intravagina methods there. The possibility of having a system for the prevention and / or treatment of uro- gynecological, such as: genitourinary syndrome urinary tract, vulvovaginal atrophy, lichen sclerosus ro-atrophic, vulvo-vaginal itching and sec- vulvo-vaginal cleanliness, which is well accepted by the patients, which does not require collaboration between the patient and numerous specialized professionals, that it is easy to administer and that it is not hormone therapy is therefore a pressing need in the market. Summary of the invention The aim of the present invention is therefore that of having a system for prevention and / or the treatment of uro-gynecological disorders, such as: genitourinary syndrome, vulvo-vaginal atrophy, lichen sclero- atrophic, vulvovaginal itching and dryness vulvo vaginal, which is well accepted by patients you, which does not require collaboration between the pa- patient and numerous specialized professionals, who is easy to administer and is not a hormone therapy. This goal is achieved by a composi- pharmaceutical or nutraceutical treatment for the prevention and / or the treatment of uro-gynecological disorders as outlined in the attached claims, which definitions form an integral part of this document description. Brief description of the Figures The invention will be better understood from the following detailed description of its embodiments preferred option, made by way of example and therefore not limiting in reference to the united Figures, in which: - Figure 1 (1A and 1B) shows two graphs lines representing: Figure 1A = index of Vaginal health (VHI) median (IQR) and Figure 1B = median (IQR) VAS score for pain in pa- patients treated with CO2 laser treatment only fractionated (MonaLisa Touch™) (Group 1) or with trat- fractional CO2 laser treatment (MonaLisa Touch™) and concomitant oral administration of the composi- tion according to the present invention at V0 (basal), V1 (40 days), V2 (80 days) and V3 (120 days); - Figure 2 (2A and 2B) shows two graphs lines representing the median total scores (IQR) for subjective symptoms (Figure 2A) and se- objective findings (Figure 2B) of the patients in the Group 1 (radiofrequency only) and Group 2 (radiofrequency sequence and co-administration of the composition (according to the present invention) to T0, T1 and T2. In the attached Figures, equal or similar elements will be indicated using the same references numeric. Detailed description of the invention The object of the present invention is a compo- pharmaceutical or nutraceutical product, in the form of dosage unit for oral administration, com- taking collagen peptides, astraga powder- I, Centella asiatica extract, mononucleotides, hyaluronic acid, for use in prevention and / or the treatment of selected uro-gynecological disorders among: genitourinary syndrome, vulvovagi- atrophy nal, lichen sclero-atrophic, pruritus vulvo-vagina- the, vulvo-vaginal dryness. As known to the expert technician in the sector, with the term “nutraceutical” refers to a composition tion including substances derived from plants, foods and microbial sources. With reference to this description and to the the united claims, with the term “astragalus” we mean Astragalus, a genus of plants belonging to belonging to the Fabaceae (or Leguminosae) family, widespread in the temperate regions of the northern hemisphere. Over 3000 species belong to this genus. With reference to this description and to the the united claims, with the term “centella “asiatica” refers to a medicinal plant belonging to belonging to the Apiaceae or Umbelliferae family. Native to the Asian continent of the belt pantropical, also grows in Australia and Africa ca, especially in humid and marshy environments. Today It is particularly widespread in India. Commonly known as- named "tiger of the meadow", it contains within it a series of pentacyclic triterpenoids called generically centelloids, produced as metabolites secondary. Among these are asiaticoside, madecasso- side and centelloside. As known to the expert technician in the sector, the lichen sclerosus is an inflammatory disease chronic ria affecting the skin and mucous membranes especially of the anogenital area; it is considered a multifactorial inflammatory disease likely bile autoimmune etiopathogenesis that affects mostly genetically predisposed individuals. Vaginal itching and vulvovaginal dryness nal, in addition to being two uro-gynecological disorders in themselves, they can be related symptoms and coexisting with other uro-gynecological disorders mentioned. Collagen is one of the proteins most important structural elements of our organism. physiological aging process of our organism begins around the age of 35, when the syn- collagen thesis begins to undergo alteration both quantitative and qualitative. This alteration it causes a loss of tone and elasticity of the connective tissue resulting in the appearance of different signs and symptoms depending on the district body affected. These changes, normally slow mind, they undergo an acceleration in the period of menopause due to hormonal rearrangement. Even the female genitals undergo, like all other organs, physiological changes of shape and volume, passing through the various stages of growth: from adolescence to maturity sexuality, to possible pregnancies, up to ar- to go through menopause. The lamina propria of the vaginal mucosa, on which the lining epithelium rests, it rises in folds and is composed of dense connective tissue (rich in collagen fibers), elastic fibers and from the vascular-lymphatic network immersed in the matrix extracellular. The most representative cellular population presented in the vaginal connective tissue is that fibroblasts, which have the task of producing and process both the fibrillar component and the extracellular matrix, made up of glycoproteins ne, glycosaminoglycans and proteoglycans. The matrix exerts profound control over the cells con- nectivals since the latter detect and respond constantly to the changes in the environment that surrounds through interaction with receptors membrane, the integrins, which, once activated, transfer information from the matrix to the cells lule, influencing its activity, metabolism and the physiological cell cycle. After having elaborated the extracellular constituents, the fibroblasts remain are quiescent until a state of catabolism will stimulate them to become metabolically active again. integrins can also respond to stimulation by several exogenous matrix proteins, such as, advantageously, collagen peptides of the- the composition according to the present invention which they are mistakenly exchanged as residues, now degraded, of collagen produced by the body same. To balance this false loss, the fi- broblasts synthesize collagen and matrix ex novo extra-cellular which restores firmness, elasticity sticity and hydration of the vaginal mucosa. Advantages joyfully, therefore, the collagen of the composition according to the present invention it is capable of in- influence the metabolism of endogenous collagen, increasing firmness, elasticity and degree of hydration tissues of the vaginal mucosa. The col- composition according to this in- invention can be of any origin but preferably It is probably of animal origin (such as for example bovine, ovine, porcine or marine collagen) or vegetal the. Preferably the collagen of the composition according to the present invention comes from sources safe and certified and preferably one of the 28 types of collagen identified so far in the state of art. Even more preferably is collagen type I, type II or type III. Advantageously, astragalus powder and the extract of centella asiatica contained in the composition according to the present invention stimula- they promote the endogenous synthesis of collagen and acid hyaluronic acid. They also reduce the degradation and mi- improve the absorption of proline and glucosamine amplifying the effectiveness of collagen peptides. Astragalus powder can be powdered any part of the plant. Centel- extract Asian can be any type of extract of gotu kola having any titration tion. Advantageously, the hyaluronic acid contained in the composition according to the present invention contributes to the structural stability of the tissue connective tissue and has a hydrating action that con- helps maintain shape, plasticity and turgor of the vaginal mucosa. Hyaluronic acid of the composition according to the present invention It can be of animal or vegetable origin and can have king of any molecular weight. Advantageously, the nucleotides of the composi- tion according to the present invention are nucleoti- of products in controlled environments following the more rigorous procedures to ensure the highest safety standards, have important functions plastic-reconstructive (each new cell re- asks for around 1 billion to set itself up), it is com- They carry immunomodulatory effects and exert an effect aimed at maintaining the integrity of the mucous membrane intestinal and vaginal. The composition according to the present invention It is therefore, advantageously, a far-reaching composition maceutical or nutraceutical with trophic action on the vaginal mucosa and on the urethral epithelium, which sti- stimulates the endogenous production of collagen and elasti- na. It is indicated in the prevention and treatment of thinning and loss of elasticity of uro-gynecological tissues and in sexual disorders associated with them, possibly also in combination with pharmacological and physical therapies. The composition according to the present invention It is therefore a composition for use in the prevention tion and / or in the treatment of uro- gynecological selected from: genitourinary syndrome, vulvo-vaginal atrophy, sclero-atrophic lichen, vulvovaginal itching, vulvovaginal dryness. According to a preferred embodiment of the composition according to the present invention, the di- urogynecological disorder is preferably lichen sclero-atrophic. According to one embodiment alternative of the composition according to this invention, the uro-gynecological disorder is preferi- genitourinary syndrome. According to a alternative embodiment of the composi- tion according to the present invention, the disturbance uro-gynecological is preferably vulvo atrophy vaginal. According to one embodiment al- alternative to the composition according to this invention, the uro-gynecological disorder is preferi- vulvovaginal itching. According to a alternative embodiment of the composi- tion according to the present invention, the disturbance uro-gynecological is preferably dryness vulvo vaginal. According to a preferred embodiment of the composition according to the present invention, the composition preferably comprising: - from 1 g to 10 g of collagen peptides, - 1 mg to 2 g of astragalus powder, - 1 mg to 2 g of gotu kola extract, of which preferably from 0.005 mg to 10.08 mg of total saponins and from 0.008 mg to 16 mg of asiatic- side. - from 1 mg to 2 g of mononucleotides, - from 1 mg to 1 g of hyaluronic acid. According to a preferred embodiment of the composition according to the present invention the composition preferably comprising: - 2.5 g of collagen peptides, - 250 mg of astragalus powder and extract gotu kola, - 100 mg of mononucleotides, - 75 mg of hyaluronic acid. According to a preferred embodiment of the composition according to the present invention, the composition also comprising, preferably glucosamine, preferably 1 mg to 2 mg g of glucosamine, even more preferably 500 mg of glucosamine. As known to the expert technician in the sector, the Glucosamine is an aminomonosaccharide and one of the main precursors of protein synthesis glycosylated and lipids. It is a precursor of hyaluronic acid. Glucosamine is attributed with functions anti-inflammatory. It is also a substance which, being a precursor of hyaluronic acid, co, plays a proactive role in the prevention of de- skin blemishes typical of aging, such as wrinkles and micro-wrinkles, it contributes to the stabili- structural nature of the connective tissue and exercises a hydrating action that helps maintain the shape, plasticity and turgor of the mucosa va- ginal. According to a preferred embodiment of the composition according to the present invention i collagen peptides are preferably peptides of hydrolyzed collagen and mononucleotides are RNA mononucleotides obtained from yeast by biotechnology. Advantageously, preclinical studies have demonstrated layer that, although cellular integrins can interact with a variety of collagen peptides generic, hydrolyzed collagen peptides inte- react optimally with cellular integrins lari producing a strong activation signal and long-lasting in target cells. According to a preferred embodiment of the composition according to the present invention: - collagen peptides are preferably pep- hydrolyzed collagen tides, - astragalus powder is preferably powder of astragalus root, - Gotu kola extract is preferably gotu kola leaf extract, - mononucleotides are preferably chosen from: 5'-AMP, adenosine 5'-monophosphate free acid; 5'-CMP, cytidine free acid 5'-monophosphate; 5'-UMP, uridine 5'-monophosphate disodium salt; 5'-GMP, guanosine 5'-monophosphate disodium salt; 5'-IMP, inosine 5'-monophosphate disodium salt, and mixtures of two or more of these, - hyaluronic acid is preferably hyaluronic acid- ronic acid having a molecular weight between 3 kDa and 10 kDa. Preferably, the composition according to the The present invention comprises a mixture of five of the above mentioned eutrophic nucleotides derived from the enzymatic hydrolysis of yeast RNA. Advantageously, hyaluronic acid, being preferably very low weight hyaluronic acid molecular (3-10 kDa), takes on a biological role important by exerting different effects on the com- cellular bearing and a different penetration into the fabrics. A study conducted on the capacity hyaluronic acid to cross the epithelium intestinal has shown that only the one with weight molecular weight lower than or equal to 5 kDa is able to at- cross the intestinal barrier more easily and that absorption is proportional to its concentration traction. The composition according to the present invention can be administered at any time of the day (morning, afternoon or evening). Preferably- the use of this composition involves the administration extraction of 2.9 g and 11.7 g of composition according to the present invention. Even more preferably from 2.9 g to 8.7 g. Even more preferably from 2.9 ga 5.8 g. Even more preferably it is 2.9 g. Preferably the administration is 2.9 g of composition according to the present invention, in any time of the day, for 4 months conse- cutivi. The administration can be repeated at distance of 4 months, for a total of 2 cycles of treatment per year. Preferably, the composition according to the This invention is for oral administration in a human subject who is at the same time subjected I am, or have been, subjected to laser treatment fractionated or pulsed carbon dioxide (CO ) radio frequency for the treatment of the syndrome genitourinary tract of menopause. As known to the expert technician in the sector, carbon dioxide (CO ) laser treatment is a fractional ablative treatment, which promotes the selective photothermolysis targeting mole- water colas inside the cells. While the Radio frequency pulse treatment is a me- non-invasive therapy that uses a specific system radio frequency system. This high-frequency system energy heats the tissues deeply through high frequency electromagnetic waves, so to stimulate collagen and increase turgidity of the tissues, improving their circulation and restoring ensuring adequate blood supply to ensure also provide better hydration and breathability tion of the vaginal mucosa. Preferably, the anim- laser treatment fractionated carbon dioxide (CO ) is conducted, for about 20 minutes, preferably using pulses having a power between 20 W and 50 W, infra- halfway through rest times between 300 µs and 1500 µs. Preferably, pulse treatment radio frequency is conducted, for about 15-30 minutes, preferably using pulses having power between 20 W and 35 W, interspersed with periods of rest of about 500 ms. As described above, each component of the composition according to the present invention has di- shown to exert the following effects: - collagen peptides influence the metabo- lysm of endogenous collagen thus increasing the compactness, elasticity and degree of hydration of uro-gynecological tissues; - astragalus powder and cen- extract Asian tella stimulates endogenous synthesis both collagen and hyaluronic acid; - hyaluronic acid contributes to stability structural of the connective tissue and exercises a hydrating action that helps maintain to understand the shape, plasticity and turgidity of the the uro-gynecological mucosa; - mononucleotides have a plastic function- reconstructive useful for maintenance of the integrity of the uro-gynecological mucosa. The composition according to the present invention, being a composition that includes all the sub- said components, is able, advantageously, to exert all the above effects. Surprisingly- mind, moreover, the characteristic of understanding in a unique composition of collagen peptides, powder of astragalus, centella asiatica extract, mono- nucleotides and hyaluronic acid leads to the further advantage of generating a synergistic effect between all the components of the composition: the powder of astragalus and centella asiatica extract stimulate by both the synthesis of endogenous collagen and the synthesis of endogenous hyaluronic acid, amplify the effectiveness of both collagen peptides and of hyaluronic acid of the composition according to the present invention, thus contributing to also amplify the effectiveness of the nucleotides of the- the composition according to the present invention as maintainers of the integrity of the uro-mucosa gynecological. The composition according to the present invention therefore presents the advantages of being a composi- pharmaceutical or nutraceutical treatment for the prevention and / or the treatment of uro-gynecological disorders, such as: genitourinary syndrome, vulvo-vaginal atrophy, lichen sclero- atrophic, vulvovaginal itching and dryness vulvo vaginal, well accepted by patients, the whose administration and therefore whose pre-effect ventilation and / or treatment does not require collaboration relationship between the patient and numerous professionals specialized, it is easy to administer and it is not hormone therapy. When the composition according to this in- The invention also includes glucosamine, the compo- situation advantageously demonstrates a greater ef- preventive and / or treatment effect against of uro-gynecological disorders, such as: genitourinary syndrome, vulvovaginal atrophy, lichen sclerosus, vulvovaginal itching and vulvo-vaginal dryness. This major preventive and / or treatment effect is mainly due to the fact that glucosamine is a pre- Hyaluronic acid slider. With glucosamine in fact, anti-inflammatory functions are attributed to ries. It is a substance which, being a precursor of the a- hyaluronic acid, contributes to structural stability connective tissue and exerts an action moisturizer that helps maintain shape, plasticity and turgor of the vaginal mucosa. When the composition according to this in- The drug is administered orally to a subject human who is at the same time subjected, or has been subjected to carbon dioxide laser treatment fractionated or radiofrequency pulsed (CO) sequence for the treatment of genito- urinary tract of menopause, the composition according to The present invention advantageously demonstrates, a further greater preventive and / or treatment for genito- urinary tract of menopause. This greater effect preventive and / or treatment is mainly do- due to the synergistic effect that has been shown to be services when the composition according to this invention is administered to a human subject which is at the same time subjected, or has been subjected toposto, carbon dioxide laser treatment (CO ) fractionated or with radio frequency pulses. Favorite examples of the realization of the This invention is given for information purposes only and is not limiting, present in the following, are therefore provided as examples of the preventive and / or composition treatments according to this invention when administered to a subject human who is at the same time subjected, or has been subjected to carbon dioxide laser treatment fractionated or radiofrequency pulsed (CO) sequence. Examples EXAMPLE 1: Preventive and / or treatment effect of the composition according to the present invention when administered orally to a subject human who is at the same time subjected, or has been subjected to carbon dioxide laser treatment fractionated nica (CO ) for the treatment of syn- genitourinary syndrome of menopause. Study design and population A cohort study was conducted on 20 women menopausal volunteers over the age of 50 with a diagnosis of GSM. All patients were subjected to cervical-vaginal cytological screening performed within a year and a negative urine culture. Those who were suffering from vulvovaginal infections, infections of the bladder or who were presenting bleeding- abnormal uterine ment. The patients were sub- divided, randomly, into two groups: the group 1, consisting of 10 patients, was subjected to three sessions of carbon dioxide laser treatment fractionated bonica (CO ) (MonnaLisa Touch ™), dista- 40 days apart. Group 2, also composed of 10 patients, was subjected I'm going through the same three laser treatment sessions to fractionated carbon dioxide (CO ) (MonaLisa Touch ™), spaced 40 days apart, and in combination with laser treatment it was administered to them daily (for 120 days) composition according to the present invention containing 2.5 g collagen peptides, 75 mg of acid hyaluronic acid, 250 mg of astragalus powder and gotu kola extract and 100 mg of mononu- cleotides. Outcome measurements and study timing For all patients, data were collected in a prospectively the following data into an electronic database nico: age (years), body mass index (BMI; kg / m ), education level, marital status, gravi- dances, age of menopause and any comorbidities- ity, including history of previous interventions surgical. Patients were evaluated in four key time points: - V1, is the beginning of the study and corresponds to the first session of CO2 laser treatment fra- for both groups and at the beginning of the oral administration of the composition according to the present exclusive invention- mind for Group 2; - V2 and V3, programmed respectively at the second second and third session of laser treatment; - V4, corresponding to 40 days after the last laser treatment session and the end of the oral administration of the composition se- according to the present invention for Group 2. The evaluation took into account the se- GSM, the perception of pain related to vaginal atrophy and sexual function. GSM signs were assessed using the vaginal health index (VHI) before each fractional CO2 laser treatment session (V1, V2 and V3) and 40 days after the last one (V4). The VHI has evaluated each of the following characteristics on a scale from 1 (worst case scenario) to 5 (worst case scenario) better): vaginal elasticity, secretions, level of pH, epithelial integrity and hydration levels ne. Total scores for VHI ranged from 5 to 25, with a cut-off of <15 adopted to indicate a va- atrophic gina. The perception of pain is related at GSM was evaluated through Visual Ana- logue Scale (VAS) (0-10) before each session of fractional CO laser treatment (V1, V2 and V3) and 40 days after the last (V4). Sexual function was evaluated through the administration of the Female Sexual Function Index (FSFI) questionnaire before the first laser treatment session CO fractionated (V1) and 40 days after the last (V4). As a secondary measure, adherence was assessed of patients, of both groups, using a survey dedicated to satisfaction, administered at the end of the study (V4), where the scores va- they come back between 0 (totally dissatisfied, no be- perceived satisfaction) and 20 (totally satisfied). Furthermore, any events were documented adverse events reported during the study. Treatments MonaLisa fractional CO2 laser treatment TouchTM (DEKA, Florence, Italy) is a treatment fractionated ablative intravaginal which is delivered every 30-45 days for three consecutive months. Every Treatment session lasts approximately 20 minutes. The im- micro-ablative fractional CO laser stations used in this study for the treatment of vaginal canal are as follows: D-Pulse mode, dot power 40 W; dwell time 1000 μs and spa- 1000 μm point thickness. While for the treatment of the vaginal entrance the settings have been the following: dot power 24W; residence time, 400 μs; dot spacing 1000 μm. The procedure It was performed on an outpatient basis and did not no specific preparation or anesthesia is required approx. The patients were placed in a position of dorsal lithotomy. It was recommended to avoid the vaginal sexual intercourse for at least three days after laser application in order to prevent an inflammatory reaction that could have lasted up to 48 hours. Only patients in Group 2 had I did not receive the administration at the same time oral of the composition according to the present invention tion. The composition was administered a once a day, starting from V1 for a duration of 120 days. Baseline characteristics of patients The characteristics of the patients are described in detail in Table 1. Overall, the median age was 54 (IQR: 52 – 59) years and the BMI (body mass index) median was 23.5 (IQR: 22.1 – 25.7) kg / m . There were no differences significant differences in demographic characteristics and clinical data between the different treatment groups to. Outcome measures: Va-Health Index hygienic At the initial level (V1) the median VHI was 9.00 for Group 1 and 10.00 for Group 2 (p=0.4). During treatment, the VHI for the Group 1 increased to 10.50, 14.00 and 16.50 resp. tively to V2, V3 and V4; the improvements for the Group 2 were more pronounced, with scores rising to 13.50, 18.00 and 21.50 respectively V2, V3 and V4 (Table 2). As shown in Figure 1A, the difference in VHI values ​​between the currency- final (V4) and initial (V1) action was higher for women who received the treat- combined chin (Group 2) compared to those that received only the CO2 laser treatment fra- zionato (Group 1): =11.00 vs. = 8.50, p=0.005. Women in Group 2 achieved a VHI > 15 (vaginal atrophy cut-off) earlier than Group 1 (V3 vs V4). Measuring outcomes: measuring pain The median VAS at the initial level (V1) for the pain was 9.00 in Group 1 patients and 8.00 in those of Group 2 (p=0.3). During the study, these scores decreased to 7.00, 6.00 and 3.00 at V2, V3, V4, respectively in Group 1 women and at 5.50, 3.50 and 1.50 at V2, V3 and V4 respectively in women of Group 2 (Table- 2). As shown in Figure 1B, the difference of the VAS values ​​between the final evaluation (V4) and the initial one (V1) was higher for women than received the combined treatment (Group 2) compared to those who received only treat- fractional CO2 laser chin (Group 1): =-7.00 vs. =-5.50, p=0.017. Outcome measures: sexual function The median FSFI, for Group 1, improved from 51.50 at the initial level (V1) to 60.50 at the end of the study and, for Group 2, from 53.50 to the initial level (V1) at 67.50 at the end of the study (Table 1). Outcome measurements: satisfaction and profit- the safety one Treatment satisfaction levels also were highest in Group 2, with a score median of 18.00 (IQR: 18.00 – 18.00) compared to 11.50 (IQR: 8.75 – 18.00) in Group 1 (p=0.047). Group 2 also scored high on each domain evaluated relative to the sum oral presentation of the composition according to the present invention: 9.00 (IQR: 8.25 – 9.75) for the flavor, 9.00 (IQR: 9.00 – 9.75) for the method of administration, 10.00 (IQR: 9.00 – 10.00) for the gastrointestinal tolerability and 9 (IQR: 9.00 – 9.75) for the duration of therapy. They were not side effects reported in both groups. Table 1 Characteristics Global Group 1 Group 2 p-value N=20 N=10 N=10 (100%) (50%) (50%) Age (years) 54 (52; 55 (48; 54 (52; 0.9 59) 60) 57) BMI (Kg / m ) 23.5 23.1 25.2 0.3 (22.1; (21; (22.7; 25.7) 24.2) 25.8) Level of 0.9 instruction High school diploma - 2 1 1 day (10.0%) (10.0%) (10.0%) High school diploma on- 6 3 3 upper (30.0%) (30.0%) (30.0%) University Degree - 12 6 6 ia (60.0%) (60.0%) (60.0%) Number of pregnant women - 1 (1; 2) 2 (0; 2) 1 (1; 2) 0.9 ze Duration of meno- 5 (3; 9) 7 (5; 5 (3; 8) 0.4 break 10) (years) Marital status 0.4 Single 6 4 2 (30.0%) (40.0%) (20.0%) Married 12 6 6 (60.0%) (60.0%) (60.0%) Separated / Divorced 10 0 (0%) 2 (10.0%) (20.0%) Previous inter- 5 2 3 0.9 surgical winds (25.0%) (20.0%) (30.0%) Table 1: Descriptive characteristics of the population action of the study. Group 1: fractional CO2 laser treatment only (MonaLisa Touch™). Group 2: laser treatment Fractionated CO (MonaLisa Touch™) and se-composition according to the present invention. Abbreviations: BMI = body mass index. 1 2 Median (IQR); n(%); Rank sum test Wilcoxon's exact rank sum test; Wilcoxon; Fisher's exact test. Table 2 Group 1 Fractional CO2 laser treatment only (MonaLisa Touch ™) V1 V2 V3 V4 VHI 10.50 14.00 9.00 (7.00 16.5 (13.5 (10.00 – (11.00 – – 11.00) – 20.00) 15.75) 19.00) VAS 9.00 (8.25 7.00 (5.25 6.00 (4.00 3.00 (2.00 – 9.00) – 8.00) – 6.00) – 4.75) FSFI 51.50 60.50 (41.25 – - - (48.25 – 63.75) 72.00) Group 2 Fractional CO2 laser treatment (MonaLisa Touch ™) and composition according to this in- invention V1 V2 V3 V4 VHI 10.00 13.50 18.00 21.50 (8.25 – (12.25 – (16.25 – (20.20 – 11.75) 15.00) 19.00) 22.80) VAS 8.00 (8.00 5.50 (5.00 3.50 (3.00 1.00 (1.00 – 9.00) – 6.00) – 4.00) – 2.00) FSFI 53.50 67.50 (46.50 – - - (61.00 – 59.75) 75.00) Table 2: Subjective symptom scores and objective signs at each specified time in the- patients treated only with laser treatment Fractionated CO (Mona-Lisa Touch™) (Group 1) and Fractional CO2 laser treatment (Mona-Lisa Touch ™) and composition according to the present invention tion (Group 2). Discussion of the results The results of this study showed: i) an objective improvement in vaginal health assessed through the VHI, ii) a self-reduction reported GSM-related pain assessed from the VAS scale and iii) an increase in function sexuality assessed through the FSFI questionnaire in both groups of patients. However, the extent of these changes has always been greater in the women of Group 2 who received the pro- combined tocollo compared to those that have received I only wanted fractional CO2 laser treatment, with statistically significant differences in median values significant even 40 days after the last session of fractional CO2 laser treatment. Furthermore, patients who underwent the protocol combined (Group 2) reported higher levels high levels of satisfaction with their treatment. EXAMPLE 2: Preventive and / or treatment effect of the composition according to the present invention when administered orally to a human subject which is at the same time subjected, or has been subjected place, to treatment with radio frequency pulses for the treatment of genito- urinary tract of menopause. Study population The study was conducted on 20 female volunteers in menopause who suffer from GSM. All patients you, who have signed an informed consent for study enrollment, data collection, and the analysis, were subjected to screening cervico-vaginal cytology performed within the year and to a negative urine culture. They were excluded from the the study those who were suffering from infections vulvovaginal, bladder infections or that was- no presenting abnormal uterine bleeding. patients were randomly assigned (1:1) in two treatment groups: 10 patients (Group 1) have only been subjected to vulvo-treatment vaginal with radio frequency (RF) pulses and 10 patients (Group 2) were subjected to treat- vulvovaginal chin with RF pulses in combination with oral administration of the composition according to the present invention. Radiofrequency treatment The transcutaneous temperature RF device controlled (TTCRF) used in this study is a bipolar RF device (SECTUM, Nrose, Neauvia) at 480kHz. The treatment program is composed of four treatments, in which each ses- sion is spaced two weeks apart. At the manipulative disposable a generous amount of was applied hyaluronic acid in the form of a gel, which functions both as a moisturizer and as a conductor. The handpiece was introduced into the vagina and the treatment was performed RF chin with an energy setting of 25- 30W continuously, with an overall life of 15 minutes from the moment the tempera- average internal vaginal temperature reached 38°C approximately, without ever exceeding 40°C. The current is was released in pulse mode (500 ms), for 15-20 minutes, with a slow, long movement the entire vaginal canal. Subsequently, always with the application of a generous amount of gel of hyaluronic acid on the vulva, the treatment is continued using the same probe always in pulse mode, performing slow movements for another 10 minutes. Treatment with administration of the composi- tion according to the present invention Only patients in Group 2 received con- temporarily a systemic treatment, with the oral administration of 2.5 g of the composition according to the present invention. The treatment is was administered once daily for four months. Evaluation of study parameters and times For all patients, the following data were prospectively recorded in an electronic database tronic: age (years), body mass index (BMI; kg / m ), education level, marital status, gravi- dances, age of menopause and any comorbidities- ity, including history of previous interventions surgical. To study the effects of treatments you on the GSM, a list of con- I'm going to use this tool to systematically evaluate five symptoms. subjective (vaginal dryness, dyspareunia, irri- burning / itching, dysuria and bleeding with sexual activity) and six objective signs (ela- nonconstipation, vaginal folds, fluid secretion, epithelial thickness, humidity and tissue color), along with vaginal pH. These assessments are were conducted in three moments: T0, which marks the ini- uncle of RF treatment for both groups, with Group 2 starting at the same time as well oral integration; T1, two months later, at the end of RF treatment; and T2, five months after T0, which provides a post-observation window treatment. The initial phase between T0 and T1 is con- focused on a direct comparison between the two Groups to observe the immediate effects of the treatment to. Each sign and symptom was evaluated on a four-level scale (0 = none / normal, 1 = mild, 2 = moderate, 3 = severe), allowing for a detailed comparison of treatment results to. Subsequently, the period extending up to T2 served as an observation phase for monitoring to achieve lasting impacts and lasting benefits of oral supplementation to RF treatment. Vaginal pH was measured using strips reactive (Vaginal Health series, Just Fitter), at the beginning of the treatment and in the same points times specified above. Consequently, to each measurement was assigned a co-score m and follows: >6.1 = –1; 5.6 to 6.0 = –2; from 5.1 to 5.5 = –3; 4.6 to 5 = –4 and <4.5 = –5. During the adverse events were also evaluated in the study. yes, product compliance and tolerance. Results Baseline demographics and characteristics stratified patient population clinics cate based on the treatment received (Group 1: RF vulvovaginal alone vs. Group 2: RF vulvovaginal- the and concomitant oral administration of the composition according to the present invention) are shown in Table 3. The total score for the subjective symptoms and objective signs evaluated in each specified time point, as well as the score- assigned to each specific domain, are mo- layers in Table 4 and Figure 2. Initially, at T0, the median total score for subjective symptoms it was 10.50 (IQR: 8.00; 11.00) vs. 11.0 (IQR: 10.25; 13.75) in patients of Group 1 and Group 2, respectively (p = 0.2). The median total score for the objec- was 12.00 (IQR: 11.25; 18.00) re- compared to 15.50 (IQR: 12.00; 18.00) in patients of Group 1 and Group 2, respectively (p=0.4). The median vaginal pH score was status of 1.5 (IQR: 1.0; 2.0) in both groups (p=0.9). At the end of RF treatment (T1), the score- median total score for subjective symptoms dropped at 4.00 (IQR: 3.25; 5.75) in patients of the Group 1 ea 3.00 (IQR: 1.50; 4.00) in patients of the Group 2 (p=0.2). The median total score for the objective signs decreased to 8.50 (IQR: 6.25; 10.00) in patients in Group 1 and at 5.50 (IQR: 2.25; 8.75) in patients of Group 2 (p=0.2). The points median vaginal pH values ​​increased to 4.5 (IQR: 4.0; 5.0) and 5.0 (IQR: 4.0; 5.0) respectively- mind in patients of Group 1 and Group 2 (p=0.6). Three months after the last treatment session with RF (T2), the median total score for the syn- subjective toms slightly increased in the pa- patients in Group 1 (5.50; IQR: 3.25; 6.00), while continued to decrease in patients in the Group 2 (1.00; IQR: 1.00; 2.00) (p<0.001). The same is happened for the objective signs: after the interruption of RF treatment in Group 1 patients The median total score increased to 10.00 (IQR: 7.25; 10.75), while it continued to decrease at 4.00 (IQR: 2.50; 4.75) in women in Group 2 (p<0.001), which after stopping the treatment with RF they continued with the administration oral presentation of the composition according to this invention for another 2 months, demonstrating, vantag- joyfully that the composition alone, when summed up administered orally, it is able to prevent and / or treat GSM. Finally, the median score of the Vaginal pH at T2 was 4.0 (IQR: 3.0; 4.0) and 4.5 (IQR: 4.0; 5.0) in Group 1 patients and of Group 2, respectively (p=0.015). No side effects have been reported. oral administration of the composition according to the present invention. Table 3 Characteristics Group 1 Group 2 p-value 1 1 N=10 (50%) N=10 (50%) Age (years) 56 (53; 58) 56 (52; 58) 0.7 BMI (Kg / m ) 25.1 (24.6; 25.6 (23.5; 0.6 25.7) 27.8) Level of 0.7 instruction High school diploma - 2 (20.0%) 4 (40.0%) day High school diploma out of 5 (50.0%) 4 (40.0%) superior University degree - 3 (30.0%) 2 (20.0%) ia Number of pregnant women - 2 (1; 3) 2 (1; 3) 0.5 ze Menopause age 51 (50; 51) 50 (50; 51) 0.8 (years) Marital status 0.9 Single 1 (10.0%) 2 (20.0%) Married 7 (70.0%) 7 (70.0%) Separated / Divorced 2 (20.0%) 1 (10.0%) Table 3: Descriptive characteristics of the population action of the study. Group 1: vulvovaginal treatment with pulse only yes to radio frequency. Group 2: vulvo-treatment vaginal with RF pulses in combination with the oral administration of the composition according to the present invention. Abbreviations: BMI = BMI of body mass. 1 2 Median (IQR); n(%); Rank sum test Wilcoxon's exact test; Fisher's exact test. Table 4 Group 1 Vulvovaginal RF T0 T1 T2 Subjective symptoms Vaginal dryness 3.00 2.00 2.00 (2.00 – (2.00 – (1.00 – 3.00) 2.00) 2.00) Dyspareunia 3.00 1.00 2.00 (2.00 – (1.00 – (1.25 – 3.00) 1.75) 2.00) Irritation / burning / itching 2.00 1.00 1.00 (2.00 – (1.00 – (1.00 – 2.00) 1.00) 1.00) Dysuria 1.50 1.00 (0 0 (0 – (1.00 – 1.00) – 1.00) 2.00) Bleeding with sexual activity 1.00 0 (0 – 0 (0 – sole (1.00 – 0) 0) 1.00) TOTAL 10.50 4.00 5.50 (8.00 – (3.25 – (3.25 – 11.00) 5.75) 6.00) Objective signs Elasticity 2.00 1.50 2.00 (2.00 – (1.00 – (1.25 – 3.00) 2.00) 2.00) Vaginal folds 2.00 2.00 2.00 (2.00 – (1.00 – (1.00 – 3.00) 2.00) 2.00) Fluid secretion 2.00 1.00 1.00 (2.00 – (1.00 – (1.00 – 3.00) 1.00) 1.75) Epithelial thickness 2.00 1.50 2.00 (1.25 – (1.00 – (2.00 – 3.00) 2.00) 2.00) Humidity 2.00 1.00 1.00 (2.00 – (1.00 – (1.00 – 3.00) 1.00) 1.00) Fabric color 2.00 1.50 2.00 (2.00 – (1.00 – (1.00 – 3.00) 2.00) 2.00) TOTAL 12.00 8.50 10.00 (11.25 (6.25 – (7.25 – – 10.00) 10.75) 18.00) Group 2 Vulvovaginal RF + compo- position according to the presen- you invention Subjective symptoms Vaginal dryness 3.00 1.00 1.00 (2.25 – (1.00 – (0.25 – 3.00) 2.00) 1.00) Dyspareunia 3.00 1.00 0 (0 – (2.00 – (0.25 – 1.00) 3.00) 1.00) Irritation / burning / itching 2.00 0 (0 – 0 (0 – (2.00 – 1.00) 0) 2.75) Dysuria 2.00 0 (0 – 0 (0 – (2.00 – 1.00) 0) 3.00) Bleeding with sexual activity 1.00 0 (0 – 0 (0 – sole (1.00 – 0) 0) 2.00) TOTAL 11.00 3.00 1.00 (10.25 (1.50 – (1.00 – – 4.00) 2.00) 13.75) Objective signs Elasticity 3.00 1.00 (0 1.00 (2.00 – – 2.00) (1.00 – 3.00) 1.75) Vaginal folds 2.50 1.00 1.00 (2.00 – (1.00 – (1.00 – 3.00) 2.00) 1.00) Fluid secretion 2.50 1.00 (0 0 (0 – (2.00 – – 1.00) 0) 3.00) Epithelial thickness 2.50 1.00 1.0 (1.00 – (1.0 – (2.00 – 3.00) 1.75) 1.0) Humidity 2.50 1.00 (0 0 (0 – (2.00 – – 1.00) 0) 3.00) Fabric color 2.50 1.00 (0 1.00 (2.00 – – 1.75) (0.25 – 3.00) 1.00) TOTAL 15.50 5.50 4.00 (12.00 (2.25 – (2.50 – – 8.75) 4.75) 18.00) Table 4: Subjective symptom scores and objective signs, at every point in time, of the pa- patients treated with vulvoradiofrequency only vaginal (Group 1) and vulvovaginal radiofrequency + oral administration of the composition according to the present invention (Group 2). Discussion of the results The four sessions of treatment with vulvo-RF vaginal, spaced two weeks apart on the other hand within two months, both alone (Group 1) both in co-administration with the compo- position according to the present invention (Group 2), have been shown to improve symptoms and signs of GSM and restore the vaginal pH. The te- combination therapy (Group 2) has, however, advantages successfully, brought to remarkably improved results better than RF treatment alone, nonetheless given the absence of statistical differences between the two groups at the end of the treatment period with RF (T1). However, in the follow-up period (T2), while Group 1 showed a resurgence of the scores for symptoms and signs, Group 2 has showed further improvement. This diver- gency was found to be statistically significant at T2, highlighting the enhanced and long-lasting benefits both combination therapy and therapy alone administration of the composition according to the pre- feels invention.

Claims

CLAIMS 1. Pharmaceutical or nutraceutical composition, in the form of dosage units for oral administration, comprising collagen peptides, astragalus powder, gotu kola extract, mononucleotides, hyaluronic acid, for use in the prevention and / or treatment of urogynecological disorders selected from: genitourinary syndrome, vulvovaginal atrophy, lichen sclerosus, vulvovaginal pruritus, vulvovaginal dryness.

2. Composition for use according to claim 1, wherein the uro-gynecological disorder is lichen sclerosus.

3. Composition for use according to claim 1 or 2, comprising: - 1 g to 10 g of collagen peptides, - 1 mg to 2 g of astragalus powder, - 1 mg to 2 g of gotu kola extract, including 0.005 mg to 10.08 mg of total saponins and 0.008 mg to 16 mg of asiaticoside, - 1 mg to 2 g of mononucleotides, - 1 mg to 1 g of hyaluronic acid.

4. Composition for use according to any of claims 1 to 3, comprising: - 2.5 g of collagen peptides, - 250 mg of astragalus powder and gotu kola extract, - 100 mg of mononucleotides, - 75 mg of hyaluronic acid.

5. Composition for use according to any of claims 1 to 4, further comprising glucosamine, preferably 1 mg to 2 g of glucosamine, even more preferably 500 mg of glucosamine.

6. Composition for use according to any of claims 1 to 5, wherein: the collagen peptides are hydrolyzed collagen peptides and the mononucleotides are RNA mononucleotides obtained from yeast by biotechnological means.

7. A composition for use according to any of claims 1 to 6, wherein: - the collagen peptides are hydrolyzed collagen peptides, - the astragalus powder is astragalus root powder, - the gotu kola extract is gotu kola leaf extract, - the mononucleotides are selected from: 5'-AMP, adenosine 5'-monophosphate free acid; 5'-CMP, cytidine 5'-monophosphate free acid; 5'-UMP, uridine 5'-monophosphate disodium salt; 5'-GMP, guanosine 5'-monophosphate disodium salt; 5'-IMP, inosine 5'-monophosphate disodium salt, and mixtures of two or more of these, - the hyaluronic acid is hyaluronic acid having a molecular weight between 3 kDa and 10 kDa.

8. Composition for use according to any of claims 1 to 7, administered at any time of the day (morning, afternoon or evening).

9. Composition for use according to any of claims 1 to 8, for oral administration in a human subject who is simultaneously undergoing, or has been subjected to, fractional carbon dioxide (CO2) laser treatment or pulsed radiofrequency laser treatment for the treatment of genitourinary syndrome of menopause.

10. Composition for use according to claim 9, wherein the use of said composition involves the administration of 2.9 g to 11.7 g of composition.

11. A composition for use according to claim 9 or 10, wherein the fractional carbon dioxide (CO2) laser treatment is conducted, preferably for about 20 minutes, using pulses having power between 20 W and 50 W, interspersed with rest times between 300 ps and 1500 ps.

12. Composition for use according to claim 9 or 10, wherein the radio frequency pulse treatment is conducted, preferably for about 15-30 minutes, using pulses having a power between 20 W and 35 W, interspersed with rest times of about 500 ms.