IT201900000343A1 - COMPOSITIONS FOR THE TREATMENT OF MENOPAUSE, OSTEOPENIA AND OSTEOPOROSIS, METABOLIC AND VASCULAR DISORDERS RELATED TO CLIMATER - Google Patents
COMPOSITIONS FOR THE TREATMENT OF MENOPAUSE, OSTEOPENIA AND OSTEOPOROSIS, METABOLIC AND VASCULAR DISORDERS RELATED TO CLIMATER Download PDFInfo
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Description
Descrizione del brevetto per invenzione industriale avente per titolo: Description of the patent for industrial invention entitled:
“COMPOSIZIONI PER IL TRATTAMENTO DI MENOPAUSA, OSTEOPENIA E OSTEOPOROSI, DISTURBI METABOLICI E VASCOLARI LEGATI AL CLIMATERIO” "COMPOSITIONS FOR THE TREATMENT OF MENOPAUSE, OSTEOPENIA AND OSTEOPOROSIS, METABOLIC AND VASCULAR DISORDERS RELATED TO CLIMATER"
La presente invenzione riguarda composizioni utili per il trattamento dei sintomi della menopausa, comprendenti estratti di piante ad attività estrogenica eventualmente associate ad altri estratti di piante medicinali, vitamine ed oligoelementi. The present invention relates to compositions useful for the treatment of menopause symptoms, comprising extracts of plants with estrogenic activity possibly associated with other extracts of medicinal plants, vitamins and trace elements.
Stato dell’arte State of the art
È noto che i sintomi associati alla menopausa, sia neurovegetativi (vampate di calore, sudorazione, cefalea) che psichici (irritabilità, depressione, disturbi del sonno), nonché l’osteoporosi, che si manifesta frequentemente nel climaterio, sono ascrivibili alla carenza di estrogeni. La terapia ormonale sostitutiva costituisce pertanto un efficace rimedio terapeutico. It is known that the symptoms associated with menopause, both neurovegetative (hot flashes, sweating, headache) and psychic (irritability, depression, sleep disturbances), as well as osteoporosis, which occurs frequently in the climacteric, are attributable to estrogen deficiency . Hormone replacement therapy therefore constitutes an effective therapeutic remedy.
La somministrazione di estrogeni non è tuttavia priva di rischi, specie a lungo termine, per la possibilità di insorgenza di tumori estrogeno-dipendenti; per questa ragione è preferibile l’assunzione di sostanze estrogeno-simili di origine vegetale a struttura simile all’estradiolo, i cosiddetti fitoestrogeni, ossia composti eterociclici contenuti nelle leguminose e nei cereali. Pertanto, l’integrazione della dieta con derivati della soia o l’assunzione dei fitoestrogeni da essa derivati rappresenta una promettente alternativa all’assunzione di estrogeni. However, the administration of estrogen is not without risks, especially in the long term, due to the possibility of developing estrogen-dependent tumors; for this reason it is preferable to consume estrogen-like substances of plant origin with a structure similar to estradiol, the so-called phytoestrogens, ie heterocyclic compounds contained in legumes and cereals. Therefore, the integration of the diet with soy derivatives or the intake of phytoestrogens derived from it represents a promising alternative to estrogen intake.
La soia è la fonte principale di estrogeni attualmente utilizzata: gli isoflavoni di soia presentano infatti un’attività estrogeno-simile ampiamente consolidata, che si rivela particolarmente efficace sia nei confronti dell’osteoporosi, grazie a un’azione di inibizione sulla tirosina chinasi, che comporta a sua volta l’inibizione dell’attività osteoclastica, con conseguente aumento della densità minerale ossea, sia nei confronti della sintomatologia post-menopausale, in particolare nella riduzione di vampate di calore, nervosismo, mal di testa e palpitazioni. Soy is the main source of estrogen currently used: soy isoflavones have in fact a widely consolidated estrogen-like activity, which is particularly effective both against osteoporosis, thanks to an inhibiting action on tyrosine kinase, which in turn, it involves the inhibition of osteoclastic activity, with a consequent increase in bone mineral density, both in relation to post-menopausal symptoms, in particular in the reduction of hot flashes, nervousness, headache and palpitations.
La Cimicifuga racemosa, una pianta della famiglia delle Ranunculaceae, è un’altra fonte di fitoestrogeni: le radici e il rizoma di Cimicifuga contengono infatti, oltre a glicosidi triterpenici, la formononetina, un estrogeno. L’estratto, generalmente titolato in glucosidi triterpenici con valori tra 0,5 e 30%, si è dimostrato efficace nel trattamento dei disturbi neuro-vegetativi associati alla menopausa e della dismenorrea [E. Ducker et al., Planta Med., 57 (1991) 420]. EP1200107 ed EP0847755 descrivono l’uso di estratti di Cimicifuga come alternative alla terapia ormonale sostitutiva. Black Cohosh, a plant of the Ranunculaceae family, is another source of phytoestrogens: the roots and rhizome of Black Cohosh contain, in addition to triterpene glycosides, formononetin, an estrogen. The extract, generally titrated in triterpene glucosides with values between 0.5 and 30%, has proven effective in the treatment of neuro-vegetative disorders associated with menopause and dysmenorrhea [E. Ducker et al., Planta Med., 57 (1991) 420]. EP1200107 and EP0847755 describe the use of Black Cohosh extracts as alternatives to hormone replacement therapy.
US 6267994 descrive l’impiego dell’estratto, in combinazione con composti ed attività antiestrogena, in particolare il tamoxifene, per il trattamento di tumori estrogeno dipendenti. US 6267994 describes the use of the extract, in combination with compounds and antiestrogenic activity, in particular tamoxifen, for the treatment of estrogen-dependent tumors.
L’associazione di formononetina con altri fitoestrogeni, ad esempio quelli derivati dalla soia, genisteina e daidzeina, è stata descritta per il medesimo impiego in US5830887, nonchè per il trattamento della sindrome pre-mestruale e della sindrome climaterica. EP 1321149 descrive associazioni di estratti di Cimicifuga racemosa con estratti di piante adattogene. The association of formononetin with other phytoestrogens, such as those derived from soy, genistein and daidzein, has been described for the same use in US5830887, as well as for the treatment of pre-menstrual syndrome and climacteric syndrome. EP 1321149 describes associations of Black Cohosh extracts with extracts of adaptogenic plants.
WO 201307807 descrive l’uso di estratti di Cimicifuga racemosa per la profilassi e il trattamento dell’osteoporosi. WO 201307807 describes the use of black cohosh extracts for the prophylaxis and treatment of osteoporosis.
KR20020037292 descrive composizioni fitoestrogene a base di estratto di Ferula tenuisecta. KR20020037292 describes phytoestrogenic compositions based on Ferula tenuisecta extract.
Le formulazioni ad oggi descritte, pur offrendo alternative sicure ed efficaci alla terapia ormonale, non permettono tuttavia il controllo di malattie croniche di origine multifattoriale, come è il caso delle degenerazioni multiple legate a menopausa e invecchiamento. Sindrome metabolica, osteoporosi e problemi neurologici sono infatti normalmente presenti in molte pazienti in post-menopausa, e richiedono pertanto approcci terapeutici basati su diversi meccanismi di azione allo scopo di rallentare la progressione delle principali manifestazioni patologiche. The formulations described to date, while offering safe and effective alternatives to hormonal therapy, do not however allow the control of chronic diseases of multifactorial origin, as is the case with multiple degenerations linked to menopause and aging. Metabolic syndrome, osteoporosis and neurological problems are in fact normally present in many postmenopausal patients, and therefore require therapeutic approaches based on different mechanisms of action in order to slow down the progression of the main pathological manifestations.
Descrizione dell’invenzione Description of the invention
Si è sorprendentemente trovato che l’associazione di un estratto di Cimicifuga racemosa con uno di Ferula sp consente di ridurre sin dalle prime somministrazioni i sintomi classici del climaterio, quali ad esempio vampate, sudorazioni, insonnia, ansia. Questa associazione ha sorprendentemente dimostrato di effetto sinergico tra i due componenti, esercitando un’attività notevolmente superiore a quella ottenuta dalla semplice sommatoria dei singoli componenti. It has surprisingly been found that the association of a black cohosh extract with one of Ferula sp allows to reduce the classic symptoms of climacteric, such as hot flashes, sweating, insomnia, anxiety from the very first administration. This association has surprisingly shown a synergistic effect between the two components, exerting an activity significantly higher than that obtained by the simple sum of the individual components.
In un suo primo aspetto, l’invenzione fornisce pertanto composizioni comprendenti un estratto di Cimicifuga racemosa e un estratto di Ferula sp. Sono preferiti gli estratti idroalcolici, disponibili in commercio da più fonti. In a first aspect, the invention therefore provides compositions comprising an extract of black cohosh and an extract of Ferula sp. Hydroalcoholic extracts, commercially available from multiple sources, are preferred.
L’invenzione, in suo ulteriore aspetto, riguarda anche l’uso delle composizioni nel trattamento dei sintomi della pre-menopausa, menopausa e post-menopausa. The invention, in its further aspect, also concerns the use of the compositions in the treatment of symptoms of pre-menopause, menopause and post-menopause.
Le specie di Ferula utilizzabili secondo l’invenzione comprendono Ferula sumbul (nota anche come Ferula moschata), Ferula hermonis, Ferula communis. The species of Ferula that can be used according to the invention include Ferula sumbul (also known as Ferula moschata), Ferula hermonis, Ferula communis.
L’estratto di Ferula sumbul è particolarmente preferito. Ferula sumbul extract is particularly preferred.
Il rapporto in peso tra estratto di Cimicifuga racemosa ed estratto di Ferula sumbul può variare da 1:2 a 1:10, preferibilmente da 1:3 a 1:7, più preferibilmente 1:5. The weight ratio between black cohosh extract and Ferula sumbul extract can vary from 1: 2 to 1:10, preferably from 1: 3 to 1: 7, more preferably 1: 5.
Le dosi unitarie in composizioni orali variano tipicamente da 10 a 100 mg per l’estratto di Cimicifuga e da 20 a 1000 mg per l’estratto di Ferula. Unit doses in oral compositions typically range from 10 to 100 mg for Black Cohosh extract and from 20 to 1000 mg for Ferula extract.
Le composizioni dell’invenzione possono essere somministrate per via orale in forma di compresse, capsule di cellulosa o di gelatina o per via topica, utilizzando opportuni eccipienti. Le composizioni dell’invenzione sono preparate con tecniche convenzionali, come descritto per esempio in Remington’s Pharmaceutical Handbook, Mack Publishing Co., N.Y. USA. The compositions of the invention can be administered orally in the form of tablets, cellulose or gelatin capsules or topically, using suitable excipients. The compositions of the invention are prepared with conventional techniques, as described for example in Remington's Pharmaceutical Handbook, Mack Publishing Co., N.Y. USA.
Gli estratti di Ferula contengono sostanze che interagiscono con i recettori degli estrogeni e che inibiscono la proliferazione di cellule tumorali di ovaio e mammella, mentre gli estratti di Cimicifuga racemosa contengono sia saponine bisdesmosidiche ad attività estrogenica (cimigenolo glucosidi), sia altre saponine che, dopo eliminazione di del residuo glucosidico dalla posizione C22, portano alla formazione di composti a struttura spirostanica ad attività progestinica. Gli estratti di Cimicifuga racemosa contengono anche vitamina K2 che ha un ruolo importante nell’osteogenesi unitamente alla vitamina D (Abstracts of Papers, 253rd ACS National Meeting & Exposition, San Francisco, CA, USA, April 2-6, 2017 (2017), CHED-526). La vitamina K2 regola il metabolismo del calcio responsabile e contribuisce al mantenimento della massa ossea. Ferula extracts contain substances that interact with estrogen receptors and inhibit the proliferation of ovarian and breast cancer cells, while the extracts of Black Cohosh contain both bisdesmoside saponins with estrogenic activity (cymigenol glucosides), and other saponins which, after elimination of the glucosidic residue from position C22, lead to the formation of compounds with a spirostanic structure with progestin activity. Black Cohosh extracts also contain vitamin K2 which plays an important role in osteogenesis together with vitamin D (Abstracts of Papers, 253rd ACS National Meeting & Exposition, San Francisco, CA, USA, April 2-6, 2017 (2017), CHED-526). Vitamin K2 regulates responsible calcium metabolism and contributes to the maintenance of bone mass.
Nelle composizioni dell’invenzione, agli estratti di Cimicifuga e Ferula possono essere vantaggiosamente associati come componenti aggiuntivi oligoelementi, Vitamine, in particolare Vitamina D e Vitamine del gruppo B, acido lipoico e/ o uno o più estratti fitoterapici, allo scopo di integrare le proprietà benefiche delle composizioni. Ad esempio, gli estratti di Vaccinium myrtillus o di Vaccinium macrocarpon, contenenti triterpeni pentaciclici e procianidine A e B migliorano la funzione vascolare nelle donne in climaterio affette da danni cardiovascolari legati al sovrappeso, caratteristico della menopausa, e da problemi legati ai sintomi della sindrome metabolica e al diabete di tipo 2; l’apporto di antiossidanti ed inibitori enzimatici di alfa-glucosidasi ed alfa amilasi a livello intestinale porta, oltre ad una modulazione del peso corporeo, al miglioramento della funzione endoteliale e ad una normalizzazione dei parametri lipidici, con particolare incremento del colesterolo HDL e riduzione della glicemia. In the compositions of the invention, the extracts of Black Cohosh and Ferula can be advantageously associated as additional components trace elements, Vitamins, in particular Vitamin D and Vitamins of group B, lipoic acid and / or one or more phytotherapeutic extracts, in order to integrate the properties beneficial of the compositions. For example, extracts of Vaccinium myrtillus or Vaccinium macrocarpon, containing pentacyclic triterpenes and procyanidins A and B improve vascular function in women in climacteric suffering from cardiovascular damage related to overweight, characteristic of menopause, and problems related to the symptoms of the metabolic syndrome. and type 2 diabetes; the intake of antioxidants and enzymatic inhibitors of alpha-glucosidase and alpha amylase in the intestine leads, in addition to a modulation of body weight, to the improvement of endothelial function and to a normalization of lipid parameters, with particular increase in HDL cholesterol and reduction of glycemia.
In alternativa o in aggiunta, le composizioni dell’invenzione possono contenere anche estratti di Citrus bergamia e Cynara cardunculus var sylvestris descritti in IT RM2007A000515; EP 2364158; WO 2010 554920. Alternatively or in addition, the compositions of the invention may also contain extracts of Citrus bergamia and Cynara cardunculus var sylvestris described in IT RM2007A000515; EP 2364158; WO 2010 554920.
Esempi di altri estratti utili ai fini dell’invenzione comprendono estratti di Olea europea, Ginkgo biloba, Citrus reticulata var clementine, Salvia officinalis, Vitis vinifera (semi), Berberis aristata. Detti estratti hanno un elevato contenuto di polifenoli che esplicano una potente azione contro i radicali liberi, oltre ad inibire a livello intestinale enzimi quali alfa-amilasi, glucosidasi e lipasi. Examples of other extracts useful for the purposes of the invention include extracts of Olea europea, Ginkgo biloba, Citrus reticulata var clementine, Salvia officinalis, Vitis vinifera (seeds), Berberis aristata. These extracts have a high content of polyphenols which exert a powerful action against free radicals, as well as inhibiting enzymes such as alpha-amylase, glucosidase and lipase in the intestine.
Gli estratti di Olea europea foglie, di Vaccinium myrtillus, di Vaccinium macrocarpum e di Salvia officinalis, oltre a contenere alte percentuali di acidi clorogenici e flavonoidi, contengono acidi triterpenici sia dell’ursano sia dell’oleanano, attivi come modulatori del sistema immunologico e come regolatori enzimatici della sintesi proteica. The extracts of Olea europea leaves, Vaccinium myrtillus, Vaccinium macrocarpum and Salvia officinalis, in addition to containing high percentages of chlorogenic acids and flavonoids, contain triterpenic acids of both ursano and oleanane, active as modulators of the immunological system and as enzymatic regulators of protein synthesis.
I diterpeni lipofili presenti nell’estratto di Salvia officinalis, quali carnosolo, acido carnosico e simili, sono in grado di attraversare la barriera emato-encefalica, dove esercitano attività antinfiammatoria e neuroprotettrice con effetti positivi su disturbi neurovegetativi e vascolari frequenti nella menopausa. The lipophilic diterpenes present in the Salvia officinalis extract, such as carnosol, carnosic acid and the like, are able to cross the blood-brain barrier, where they exert anti-inflammatory and neuroprotective activity with positive effects on neurovegetative and vascular disorders frequent in menopause.
Gli estratti di foglie di Olea europea intervengono nella riduzione dell’osteopenia e dell’osteoporosi come risultato di effetti sinergici fra verbascoside, oleoeuropeina ed i triterpeni pentaciclici acido ursolico ed oleanolico. The extracts of Olea europea leaves intervene in the reduction of osteopenia and osteoporosis as a result of synergistic effects between verbascoside, oleoeuropein and the pentacyclic triterpenes ursolic and oleanolic acid.
Per contrastare sintomi quali ansia, depressione, deficit cognitivo e mnemonico, possono essere aggiunti estratti di piante adattogene. Fra queste, è preferita la Withania somnifera che contiene i withanolidi, principi attivi dotati di potente azione inibitrice delle acetil e butirril colinesterasi, enzimi coinvolti nel funzionamento cerebrale. Si utilizzano preferibilmente estratti di Withania somnifera a contenuto in withanolidi compreso fra il 4 e 12%, preferibilmente pari a circa l’8% eventualmente in associazione con una miscela fosfolipidica contenente il 20% di fosfatidilserina. To counteract symptoms such as anxiety, depression, cognitive and memory impairment, adaptogenic plant extracts can be added. Among these, Withania somnifera is preferred, which contains withanolides, active ingredients with a powerful inhibitory action of acetyl and butyryl cholinesterase, enzymes involved in brain functioning. Withania somnifera extracts are preferably used with a withanolides content between 4 and 12%, preferably approximately 8%, possibly in association with a phospholipid mixture containing 20% phosphatidylserine.
Le quantità dei componenti aggiuntivi sopra citati potranno variare entro ampi limiti, determinati dall’esperto del settore in base alle comuni conoscenze disponibili in letteratura. The quantities of the aforementioned additional components may vary within wide limits, determined by the industry expert based on the common knowledge available in the literature.
Sperimentazione farmacologica Pharmacological experimentation
La sinergia degli estratti di Cimicifuga racemosa e di Ferula sumbul è stata dimostrata in sperimentazioni cliniche utilizzando la scala parametrica di Greene (Greene, JG. Measuring the symptom dimension of quality of life: General and menopause-specific scales and their subscale structure. In: Hormone replacement therapy and quality of life. The Parthenon Publishing Group. (Edited by: Schneider HPG) Boca Raton, London, New York, Washington. 2002: 35-43). The synergy of Black Cohosh extracts and Ferula sumbul has been demonstrated in clinical trials using the Greene parametric scale (Greene, JG. Measuring the symptom dimension of quality of life: General and menopause-specific scales and their subscale structure. Hormone replacement therapy and quality of life. The Parthenon Publishing Group. (Edited by: Schneider HPG) Boca Raton, London, New York, Washington. 2002: 35-43).
I prodotti sono stati somministrati a donne normali e in menopausa chirurgica all’insorgenza dopo dismissione del ciclo mestruale seguendo le pazienti in uno studio randomizzato in accordo alle modalità e ai criteri di protocolli convenzionali come la scala di Greene. Le pazienti sono state trattate per 1 mese con due capsule al giorno, mattina e sera, rispettivamente con 20 mg di estratto idroalcolico di Cimicifuga racemosa, con 100 mg di Ferula sumbul e con la combinazione dei due nello stesso rapporto quantitativo. The products were administered to normal and surgical menopausal women at onset after discontinuation of the menstrual cycle following the patients in a randomized study in accordance with the methods and criteria of conventional protocols such as the Greene scale. The patients were treated for 1 month with two capsules a day, morning and evening, respectively with 20 mg of hydroalcoholic extract of Black Cohosh, with 100 mg of Ferula sumbul and with the combination of the two in the same quantity ratio.
Nella Tabella 1 sono riportati i dati relativi ai dosaggi abitualmente usati per gli estratti di Cimicifuga racemosa e di Ferula sumbul, con i risultati espressi in sommatoria di punti secondo scala di Greene. Table 1 shows the data relating to the dosages usually used for the extracts of Black Cohosh and Ferula sumbul, with the results expressed in summation of points according to the Greene scale.
Nella Tabella 2 sono riportati i dati prodotti con la scala di Greene riferentisi a score su 10 pazienti per gruppo con l’analisi dei singoli parametri esaminati. Table 2 shows the data produced with the Greene scale referring to scores on 10 patients per group with the analysis of the individual parameters examined.
I dati ottenuti dimostrano la netta superiorità della combinazione dei due The data obtained demonstrate the clear superiority of the combination of the two
estratti nella loro globalità. Analizzando parametro per parametro si può extracted in their entirety. By analyzing parameter by parameter it is possible
chiaramente vedere come sintomi singoli e caratteristici del climaterio vengano clearly see how single and characteristic symptoms of the climacteric come
ridotti fino al 90 % dopo pochi giorni di trattamento. reduced by up to 90% after a few days of treatment.
Gli esempi seguenti illustreranno ulteriormente l’invenzione. The following examples will further illustrate the invention.
Esempio 1 - Capsule di gelatina molle contenenti gli estratti di Example 1 - Soft gelatin capsules containing the extracts of
Cimicifuga racemosa e di Ferula 1:5 Black Cohosh and Ferula 1: 5
Composizione unitaria Unitary composition
Ingrediente mg Ingredient mg
Estratto di Cimicifuga racemosa 20 Black Cohosh extract 20
Estratto di Ferula sumbul 100 Ferula sumbul extract 100
Lecitina di soia 150 Soya lecithin 150
Olio di lino 300 Linseed oil 300
Esempio 2 - Capsule di gelatina dura contenenti gli estratti di Cimicifuga Example 2 - Hard gelatin capsules containing Black Cohosh extracts
racemosa e di Ferula 1:5 racemosa and Ferula 1: 5
Ingrediente mg Ingredient mg
Estratto di Cimicifuga racemosa 20 Black Cohosh extract 20
Estratto di Ferula sumbul 100 Ferula sumbul extract 100
Cellulosa microcristallina 200 Microcrystalline cellulose 200
Biossido di silicio 5 Silicon dioxide 5
Magnesio Stearato 5 Magnesium Stearate 5
Esempio 3 - Compresse contenenti gli estratti di Cimicifuga racemosa e Example 3 - Tablets containing Black Cohosh extracts e
di Ferula 1:5 per il trattamento dell’osteoporosi of Ferula 1: 5 for the treatment of osteoporosis
Ingrediente mg Ingredient mg
Estratto di Cimicifuga racemosa 20 Black Cohosh extract 20
Estratto di Ferula sumbul 100 Ferula sumbul extract 100
Estratto di Olea europea foglie 20% oleoeuropeina 200 European Olea leaf extract 20% oleoeuropein 200
Vitamina D 500 Vitamin D 500
Cellulosa microcristallina 200 Microcrystalline cellulose 200
Biossido di silicio 5 Silicon dioxide 5
Magnesio stearato 5 Magnesium stearate 5
Esempio 4 - Compresse contenenti gli estratti di Cimicifuga racemosa e Example 4 - Tablets containing Black Cohosh extracts e
di Ferula 1:5 per il trattamento del deficit cognitivo of Ferula 1: 5 for the treatment of cognitive impairment
Ingrediente mg Ingredient mg
Estratto di Cimicifuga racemosa 20 Black Cohosh extract 20
Estratto di Ferula sumbul 100 Ferula sumbul extract 100
Estratto di Citrus Bergamia R.&P. 200 Citrus Bergamia R. & P extract. 200
Estratto di Withania somnifera 8% Withanolidi 120 Withania somnifera 8% Withanolidi 120 extract
Fosfolipidi 20% Fosfatidilserina 200 Phospholipids 20% Phosphatidylserine 200
Vitamine gruppo B 20 Vitamins group B 20
Cellulosa microcristallina 200 Microcrystalline cellulose 200
Biossido di silicio 5 Silicon dioxide 5
Magnesio stearato 5 Magnesium stearate 5
Esempio 5 - Compresse contenenti gli estratti di Cimicifuga racemosa e Example 5 - Tablets containing Black Cohosh extracts e
di Ferula 1:5 per il trattamento di dismetabolie cardiovascolari. of Ferula 1: 5 for the treatment of cardiovascular dysmetabolies.
Ingrediente mg Ingredient mg
Estratto di Cimicifuga racemosa 20 Black Cohosh extract 20
Estratto di Ferula sumbul 100 Ferula sumbul extract 100
Estratto di Citrus Bergamia R.&P. 200 Citrus Bergamia R. & P extract. 200
Estratto di Berberis aristata 20% berberina 150 Berberis aristata extract 20% berberine 150
Estratto di Cynara cardunculus var sylvestris 100 Cynara cardunculus var sylvestris extract 100
Biossido di silicio 5 Silicon dioxide 5
Magnesio stearato 5 Magnesium stearate 5
Cellulosa microcristallina 200 Microcrystalline cellulose 200
Esempio 6 - Compresse contenenti gli estratti di Salvia officinalis e di Example 6 - Tablets containing the extracts of Salvia officinalis and of
Ferula 1:1 Ferula 1: 1
Capsule di gelatina molle da 650 mg Soft gelatin capsules of 650 mg
Ingrediente mg Ingredient mg
Estratto di Cimicifuga racemosa 20 Black Cohosh extract 20
Estratto di Salvia officinalis 100 Salvia officinalis extract 100
Estratto di Ferula sumbul 100 Ferula sumbul extract 100
Lecitina di soia 150 Soy Lecithin 150
Olio di lino 300 Linseed oil 300
Claims (8)
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| IT102019000000343A IT201900000343A1 (en) | 2019-01-10 | 2019-01-10 | COMPOSITIONS FOR THE TREATMENT OF MENOPAUSE, OSTEOPENIA AND OSTEOPOROSIS, METABOLIC AND VASCULAR DISORDERS RELATED TO CLIMATER |
| PCT/IB2020/050111 WO2020144588A1 (en) | 2019-01-10 | 2020-01-08 | Compositions for treatment of the menopause, osteopenia and osteoporosis, and menopause/related metabolic and vascular disorders |
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| CN120570386A (en) * | 2025-08-06 | 2025-09-02 | 内蒙古蒙牛乳业（集团）股份有限公司 | A composition, a product containing the same and its application |
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| CN115403658B (en) * | 2022-05-19 | 2024-04-23 | 首都医科大学 | Ursolic acid-Tyr-Gly-Phe-Gly-Gly, synthesis, activity and application thereof |
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