Menopause disorder synergistic phyto-nutraceutical composition
http://www.pharmcast.com/Patents200/Yr2008/June200 [2008-6-27]
Tag : Astragalus Extract
A Phytoceutical composition for the prevention and treatment ofmenopause disorders and symptoms is provided. A specificcombination of extracts of plants is taught, as well as principlesfor varying the formulations based on categorizing plants into oneof three groups, Energy, Bio-Intelligence, and Organization andselecting several plants from each group. Such combinations havesynergistic effects, with minimal side effects.
Description of the Invention
SUMMARY OF THE INVENTION
A number of known beneficial plants were classified according totheir capacity to enhance the three main elements that supportoverall health: Energy (E), Bio-intelligence (I) and Organization(O). A synergistic effect is expected when all three categories ofherbs (E, I, O) are included in a formulation, preferably at leasttwo or three or four plants from each category. Thus, oneembodiment of the invention provides a method of selectingadditional disease treating formulations according to theseprinciples. An example of a formulation prepared this way isprovided and additional formulations are being prepared and tested.As they reach menopause, a majority of women living in Westernizedcountries experience climacteric symptoms. The climacteric syndromeinvolves a variety of symptoms such as profuse sweating, insomnia,memory loss, decreased sexual drives, joint aches, and anxiety.However, amongst these symptoms, hot flashes and sweats aregenerally considered the hallmark and result in the majority of themedical consultations for this condition. Hormone replacementtherapy (HRT) has been used to remediate these symptoms. Recentstudies, however, have suggested that HRT may increase the risk ofdeveloping breast cancer and cardiovascular disease (CVD). Sinceancient times, extracts of plants have been used for women's healthto prevent menopausal symptoms. Therefore, many women are lookingfor alternative treatment options. Thus, another embodiment of theinvention provides an effective, natural composition for treatingmenopause disorders and symptoms. The composition can be usedalone, or can be combined with simultaneous use of one or morepharmaceutical compositions.
DETAILED DESCRIPTION OF THE INVENTION
"Pharmaceutically acceptable excipients" is used hereinaccording to art accepted meanings, and includes those ingredientsneeded to formulate a medicine for mammalian use, including the useof gelatin capsules.
"Synergistic" or "synergy" is used herein tomean that the effect is more than its additive property. Inpreferred embodiments, the synergy is at least 1.2, 1.5, 2,5, or 10fold.
By use of "plants," what is meant herein is that theplant (or that portion with medicinal activity) is used whole,ground, or as an extract. Also included are purified activeingredients and derivatives thereof. However, it is believed thatthe best efficacy of plants used herein is achieved with the use ofthe entire plant or its extracts, rather than with the use ofisolated active ingredients.
Further, although plants are named here according to commonly usednomenclature, with improving taxonomy plants are oftenreclassified. Whenever a plant is referenced, it includes relatedspecies with similar active ingredients.
The following examples are illustrative only and should not serveto unduly limit the invention.
EXAMPLE 1
Plant Characteristics
Menopause Disorder and Symptoms
Energy Enhancing Phytoceuticals
Ajuga turkestanica: Its main active principle turkesterone, aphytoecdysteroid possessing an 11alpha-hydroxyl group. Ecdysteroidsnormalize NADH dehydrogenase activity, enzyme which catalyzeselectron transfer from NADH to ubiquinones in the oxidativephosphorylation processes which occur at the mitochondrial level,contributing to the potential electrochemical buildup required toproduce ATP. It also normalizes the succinate dehydrogenase enzymewhich participates in the tricarboxilic acid cycle, whichtranslates to ATP synthesis and patient energy level increases[Tashmukhamedova M A, Almatov K T, Syrov V N. Comparative study ofthe effect of ecdysterone, turkesterone and nerobol on the functionof rat liver mitochondria in experimental diabetes. Vopr Med. Khim.1986; 32:24-8].
Panax quinquefolius (American Ginseng, Anchi, Canadian Ginseng,Five Fingers, Ginseng, American, North American Ginseng, Red Berry,Ren Shen, and Tienchi) is related to Panax ginseng, but is adistinct species with higher levels of ginsenoside Rb1 and withoutginsenoside Rf. These substances confer energizing propertiesbecause they increase ATP synthesis. It also has antioxidant andanti-inflammatory effects. Results of clinical research studiesdemonstrate that Panax quinquefolius improves physical and mentalperformance and increases resistance to exogenous stress factors.The incorporation of this phytomedicine provides at least 206active principles in a single therapeutic.
Pfaffia paniculata (Suma, Brazilian Ginseng, Pfaffia, Para Tudo,Corango-acu; also Hebanthe paniculata, Gomphrena paniculata, G.eriantha, Iresine erianthos, I. paniculata, I. tenuis, P. eriantha,Xeraea paniculata) contains active glycosides (beta-ecdysone andthree ecdysteroids), six different pfaffic acids, phytosterols(sitosterol and estigmasterol). Pfaffia also contains saponins and19 different amino acids, minerals, vitamins and pantoneic acid.Its germanium content probably accounts for its properties as anoxygenator at the cellular level, and its high iron content mayaccount for its traditional use for anemia. This herb increasesenergy through an increase in ATP synthesis and oxygenation at thecellular level, and it also has anabolic activity at the muscularlevel. These substances act as hormone precursors modulatingestrogen, progesterone and testosterone production (Oshima M, Gu Y.Pfaffia paniculata-induced changes in plasma estradiol-17beta,progesterone and testosterone levels in mice. J Reprod Dev. 2003;49: 175-80) and have demonstrated effectivity in the management ofdiverse conditions related to hormone unbalance such as menopause(Pitchford, Paul. Healing With Whole Foods: Asian Traditions andModern Nutrition. North Atlantic Books; 3rd Edition; 2002. ISBN:1556434308). Suma has safe estrogenic activity because of its storeof sitosterol, a compound which increases body's natural estrogen.Incorporation of Pfaffia provides 44 active principles.
Rhaponticum carthamoides (Leuzea, or Maral Root) contains a mixtureof compounds called `levseins`. Levseins represents a complex ofmore than 10 ecdysterones including 20-beta-ecdysterone,makisterone C, 24-dehydromakisterone A, carthamosterone, polypodyneB and ajugasterone C. Ecdysteroids normalize NADH dehydrogenaseactivity, enzyme which catalizes NADH electron transfer to theubiquinone in the oxidative phosphorylation processes at themitochondrial level, contributing to buildup the electrochemicalpotential used to produce ATP. It also normalizes the succinatedehydrogenase activity, enzyme which acts in the tricarboxilic acidcycle, which translates in ATP synthesis and patient energy levelincreases. In women with low levels of estrogens, Ecdysteronebehaves as an anabolic steroid mimicking the effects of thesehormones. Incorporation of this phytomedicine in a compositionprovides at least 10 active principles in a single therapeutic.
Bio-Intelligence Modulators
Aralia mandshurica (Manchurian Thorn Tree) The main activeprinciples are triterpene saponins aralosides (elatosides).Siberians traditionally preferred Aralia for immune health, toreduce stress/depression, and to improve physical and mentalperformance. Siberians would often combine Aralia with otheradaptogens for maximal stress reduction/performance enhancementbenefits. Aralia extract was included in the official RussianPharmacopoeia in 1983 as a treatment for the symptoms of stressoverload, such as fatigue, weakness, headache, libido loss,depression, immune weakness, etc. G. P. Gubina reported in 1988 a90 percent success rate--using Aralia--in 106 patients treated forvarious "asthenic" (stress overload/weakness) conditions.Aralia enhances a person's ability for memorization and prolongedconcentration. In proofreading tests, after taking this plant, adecrease in the quantity of mistakes was observed in 88 percent ofthe experimental group, while an increase in the quantity ofmistakes was observed in 54 percent of the control group. Thosetaking Aralia mandshurica exerted a strong stimulating influenceamong test subjects who displayed a great improvement in readingcomprehension, aptitude and speed. [A. A. Lebedev/Far EastScientific Center of the USSR]; [V. V. Kazakevich/Academy ofSciences, Vladivostok, Russia].
Astragalus membranaceus (Huang-Qi, Huangqi) This plant containsthree main types of active principles. Isoflavones, principalmenteFormononetin, astragalans, and astragalosides which act asmodulators of the hypothalamus-hypofisis-adrenal axis response. Italso contains linoleic acid. Formononetin has Estrogenic Receptoralpha and beta binding affinity (Halabalaki M, Alexi X, AligiannisN. Estrogenic activity of isoflavonoids from Onobrychis ebenoides.Planta Med. 2006; 72: 488-93). Dietary supplements are currentlyused to treat menopausal symptoms because of their high content ofthe mildly estrogenic isoflavones (formononetin). This compound isestrogenic in vitro and in vivo (Booth N L, Overk C R, Yao P.Seasonal variation of red clover (Trifolium pratense L., Fabaceae)isoflavones and estrogenic activity. J Agric Food Chem. 2006; 54:1277-82).
Isoflavones have a high affinity to estrogen receptor alpha(ERalpha), estrogen receptor beta (ERbeta), progesterone receptor(PR) and androgen receptor (AR). The affinity to ER has been usedas an explanation of the effects of isoflavones in the treatment ofmenopausal disorders. Biochemical analysis shows thatphytoestrogens have multiple actions beside selective estrogenreceptor modulator (SERM)-activity. They act as selective estrogenenzyme modulators (SEEMs), have antioxidant activity and interactwith transcription factors such as NF-kappaB. Furthermore, it isindicated that they have protective effects on osteoporosis and thecardiovascular system (Beck V, Rohr U, Jungbauer A. Phytoestrogensderived from red clover: an alternative to estrogen replacementtherapy? J Steroid Biochem Mol. Biol. 2005; 94: 499-518).Formononetin showed clear estrogenic activity through estrogenreceptor alpha (ERalpha) and estrogen receptor beta (ERbeta) andaffinity to progesterone (PR) and androgen (AR) receptors. In vitroassays and chemical analysis showed that theoretical estrogenicactivity expressed as equivalent E2 concentration is in the samerange as recommended for synthetic estrogens. Broader spectrum ofaction and hypothesized lower side effects by action through ERbetamake them suitable for alternative hormone replacement therapy(Beck V, Unterrieder E, Krenn L. Comparison of hormonal activity(estrogen, androgen and progestin) of standardized plant extractsfor large scale use in hormone replacement therapy. J SteroidBiochem Mol. Biol. 2003; 84: 259-68). Formononetin binds well tohuman ER beta and human ER alpha (Morito K, Aomori T, Hirose T.Interaction of phytoestrogens with estrogen receptors alpha andbeta (II). Biol Pharm Bull. 2002; 25: 48-52). Astragalus offers 38active principles in a single therapeutic.
Polygonum multiflorum (Fo-Ti, Chinese Knotweed, Chinese Cornbind,Climbing Knotweed, Flowery Knotweed, Fleeceflower, He Shou Wu) Themain constituents of Polygonum multiflorum are: emodin,chrysophanol, rhein, 6-OH-emodin, emodin-8-beta-D-glucoside,polygonimitin B,2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside, gallic acid.This pkant has been used traditionally in China for menopausesymptoms management. Polygonum has estrogenic activity (Kang S C,Lee C M, Choi H. Evaluation of oriental medicinal herbs forestrogenic and antiproliferative activities. Phytother Res. 2006Aug. 14). Another study which gives support to the reportedefficacy of Chinese medicines used for hormone replacement therapyis Zhang C Z, Wang S X, Zhang Y. In vitro estrogenic activities ofChinese medicinal plants traditionally used for the management ofmenopausal symptoms. J. Ethnopharmacol. 2005; 98: 295-300).Polygonum provides 47 active principles in a single therapeutic.
Vitex agnus castus (Chasteberry, Chaste-Tree): From the fruit ofthis plant are obtained an essential oil, linoleic acid, twoiridoid glicosides (aucubine y el agnusine); a flavone (casticin),flavonoids derived from kaempferol and quercetagine and otherflavonoids such as penduletin, vitexin and apigenin. Penduletin andapigenin, flavonoids of Vitex agnus castus are estrogeniccompounds. Both substances are specific ligands for thebeta-estrogenic receptor (Jarry H, Spengler B, Wuttke W. In vitroassays for bioactivity-guided isolation of endocrine activecompounds in Vitex agnus-castus. Maturitas. Epub Aug. 21, 2006).Extracts of Vitex agnus-castus displace estradiol from EstrogenicReceptor alpha and beta. Linoleic acid is one possible estrogeniccomponent of the extract. Linoleic acid is an Estrogenic Receptorligand. These data suggest that linoleic acid from the fruits ofVitex agnus-castus can bind to estrogen receptors and inducecertain estrogen inducible genes (Liu J, Burdette J E, Sun Y.Isolation of linoleic acid as an estrogenic compound from thefruits of Vitex agnus-castus L (chaste-berry). Phytomedicine. 2004;11: 18-23). A clinical trial on 23 menopausal patients withessential oils of Vitex agnus castus indicated strong symptomaticrelief of common menopausal symptoms. A second clinical trial on 52additional subjects appears to support the finding of the firsttrial (Chopin Lucks B. Vitex agnus castus essential oil andmenopausal balance: a research update Complement Ther NursMidwifery. 2003; 9: 157-60). Essential oils from Vitex agnus castuswere found to be effective, in menopausal balance (Lucks B C,Sorensen J, Veal L. Vitexagnus-castus essential oil and menopausalbalance: a self-care survey. Complement Ther Nurs Midwifery. 2002;8: 148-54). Vitex agnus preparations are commonly used for thetreatment of menopausal symptoms.
Organizational Improvers
Angelica sinensis (Dong quai or Angelica, also Angelicaarchangelia, Angelica pubescens and Angelica sylvestris Can qui,Angelica china, dangdanggui, dang gui, dong quai, duong qui,handanggui, hashyshat almalak, kara toki, langdu danggui, min-gui,tang-kuei, tangkuei, ta{grave over ( )}n q ui) Contains terpenes(terpenes, mainly .beta.-phellandrene, with .beta.-bisabolene,.beta.-caryophyllene, .beta.-phellandrene, .alpha.- and.beta.-pinene, limonene, linalool, borneol, acetaldehyde,menthadienes and nitromenthadienes), macrocyclic lactones(including tridecanolide, 12-methyl tridecanolide,pentadecanolide), phthalates (such as hexamethylphthalate),coumarins (especially furocoumarin glycosides such as marmesin andapterin), angelicin and byakangelicin derivatives (osthol,umbelliferone, psoralen, bergapten, imperatoren, xanthotoxol,xanthotoxin, oxypeucedanin and more), as well as various sugars,plant acids, flavonoids, and sterols. It also, contains alkylphthalides (Ligustilide); terpenes, phenylpropanoids (ferulic acid)and benzenoids. The results of a study demonstrated the estrogenicnature of the extract of Angelica (Circosta C, Pasquale R D,Palumbo D R. Estrogenic activity of standardized extract ofAngelica sinensis. Phytother Res. 2006; 20: 665-9). Aplacebo-controlled trial on 55 postmenopausal women who complainedof hot flushes and refused hormonal therapy showed a significantdifference between the study group and the control group in thedecrease in number and intensity of hot flushes from baseline tocompletion of treatment. There was also a marked alleviation ofsleep disturbances and fatigue (Kupfersztain C, Rotem C, Fagot R.The immediate effect of natural plant extract, Angelica sinensisand Matricaria chamomilla (Climex) for the treatment of hot flushesduring menopause. A preliminary report. Clin Exp Obstet Gynecol.2003; 30: 203-6). Dong quai showed weak Estrogen Receptor bindingand Progesteron Receptor and pS2 mRNA induction. These data suggesta potential use in the treatment of menopausal symptoms (Liu J,Burdette J E, Xu H. Evaluation of estrogenic activity of plantextracts for the potential treatment of menopausal symptoms. JAgric Food Chem. 2001; 49: 2472-9). Angelica provides 70 activeprinciples.
Cimicifuga racemosa (Black Cohosh, Black Snakeroot): Key activeconstituents are: triterpene glycosides (containing a cyclopropanering) including acetein, cimicifugoside and racemoside; isoflavonesincluding formononetin; aromatic acids including isoferulic acidand salicylic acid. Also tannin, resin (cimicifugin), ranunculin,fatty acids, starch and sugars. A multicenter, randomized,placebo-controlled, double-blind, parallel group study wasconducted in 122 menopausal women. The results indicate asuperiority of Cimicifuga racemosa extract compared to placebo inpatients with menopausal disorders (Frei-Kleiner S, Schaffner W,Rahlfs V W. Cimicifuga racemosa dried ethanolic extract inmenopausal disorders: a double-blind placebo-controlled clinicaltrial. Maturitas. 2005; 51: 397-404). A clinical trial studied thechanges in subjective symptoms of menopause in 2016 women treatedwith an extract of Cimicifuga racemosa. The most favorable changeswere found in hot flashes, sweating, insomnia, and anxiety. Theextract of C. racemosa was found to be effective in the alleviationof menopausal symptoms (Vermes G, Banhidy F, Acs N. The effects ofremifemin on subjective symptoms of menopause. Adv Ther. 2005; 22:148-54). In a randomized clinical controlled study on climactericcomplaints, the extract of Cimicifuga racemosa significantlyreduced the number of hot flushes per day and vasomotor symptoms.CONCLUSIONS: CR may be a valid alternative in the management ofclimacteric complaints in those women who cannot be treated with orjust refuse conventional strategies (Nappi R E, Malavasi B, BrunduB. Efficacy of Cimicifuga racemosa on climacteric complaints: arandomized study versus low-dose transdermal estradiol. GynecolEndocrinol. 2005; 20: 30-5). Black cohosh has been used in the USfor over 100 years. Review of the published clinical data suggeststhat cimicifuga may be useful for the treatment of menopausalsymptoms, such as hot flashes, profuse sweating, insomnia, andanxiety (Mahady G B. Black cohosh (Actaea/Cimicifuga racemosa):review of the clinical data for safety and efficacy in menopausalsymptoms. Treat Endocrinol. 2005; 4: 177-84). Osmers R, Friede M,Liske E. Efficacy and safety of isopropanolic black cohosh extractfor climacteric symptoms. Obstet. Gynecol. 2005; 105: 1074-83. Thisrandomized, multicenter, double-blind clinical trial compared theefficacy and tolerability of the black cohosh extract in thetreatment of climacteric complaints compared with placebo in atotal of 304 patients. The results showed that the black cohoshextract was more effective than placebo and clinically relevant.Cimicifuga contains at least 45 active principles in a singletherapeutic.
Dioscorea villosa (Mexican wild yam, china root, colic root,rheumatism root, huesos del diablo, yuma.) contains steroidsapogenins (dioscine, dioscorin and diosgenine) as the main activeprinciples. It also contains salts and minerals, such as: aluminum,calcium, chrome, cobalt, iron, selenium, silica, sodium, tin, zinc,magnesium, manganese, phosphorus and potassium; and vitamins:ascorbic acid, beta-carotene, niacin, riboflavin and thiamine.Diosgenine can be transformed into pregnenolone, and progesterone[Gareth, Thomas. Medicinal Chemistry. John Wiley & Sons; Firstedition December 2000. ISBN: 0471489352]. The starting material forthe production of progesterone is diosgenin obtained from a numberof Dioscorea species (a plant source). Diosgenin may be convertedto pregnenolone acetate by a series of steps. Wild yam is used as aprecursor in the manufacture of "natural progesterones".Natural progesterone products help reduce hot flashes or improvevaginal health [Tagliaferri, Mary. The New Menopause Book. AveryPublisher; March, 2006]. A clinical controlled trial in 24postmenopausal women showed that Dioscorea significantly increasesserum concentrations of estrone, sex hormone binding globulin, andestradiol. Although the exact mechanism is not clear, Dioscoreaimproves the status of sex hormones (Wu W H, Liu L Y, Chung C J.Estrogenic effect of yam ingestion in healthy postmenopausal women.J Am Coll Nutr. 2005; 24: 235-43). The incorporation of thisphytomedicine provides at least 29 active principles in a singletherapeutic.
Linum usitatissimum (Flaxseed, Flax, Linseed) Phytoestrogens arediphenolic compounds that are present in several plants eaten byhuman beings. Flaxseed is particularly abundant source ofphytoestrogens. Phytoestrogens have been shown to have significantestrogen agonists/antagonists effects in animals and humans. Thereis epidemiological, laboratory and clinical evidence whichindicates that phytoestrogens, like certain selective estrogenreceptor modulators, have a positive effect on the lipoproteinprofile and bone density. They might also improve some of theclimacteric symptoms. (Brzezinski A, Debi A. Phytoestrogens: the"natural" selective estrogen receptor modulators? Eur JObstet Gynecol Reprod Biol. 1999; 85: 47-51). Phytoestrogens, whichare abundant in flaxseed, have chemical structures resembling thoseof endogenous estrogens and have been shown to exert hormonaleffects. A clinical, randomized, controlled trial in 46postmenopausal women supplemented with either a placebo, soy, orflaxseed for 16 wk showed that urinary concentrations of2-hydroxyestrone increased significantly in the flaxseed group. Inthe soy and placebo groups, no significant correlation wasobserved. CONCLUSIONS: Supplementation with flaxseed modifiesurinary estrogen metabolite excretion to a greater extent than doessupplementation with an equal amount of soy (Brooks J D, Ward W E,Lewis J E. Supplementation with flaxseed alters estrogen metabolismin postmenopausal women to a greater extent than doessupplementation with an equal amount of soy. Am J Clin Nutr. 2004;79: 318-25). A clinical, randomized, controlled trial showed thatFlaxseed is as effective as oral estrogen-progesterone to improvemild menopausal symptoms. (Lemay A, Dodin S, Kadri N. Flaxseeddietary supplement versus hormone replacement therapy inhypercholesterolemic menopausal women. Obstet. Gynecol. 2002; 100:495-504). A clinical, randomized, controlled trial examined theeffects of flaxseed consumption on urinary estrogen metaboliteexcretion in 28 postmenopausal women showed that Flaxseedsupplementation significantly increased urinary 2-OHEstrogenexcretion and the urinary 2/16 alpha-OHE1 ratio. Results suggestprotective effects in postmenopausal women (Haggans C J, Hutchins AM, Olson B A. Effect of flaxseed consumption on urinary estrogenmetabolites in postmenopausal women. Nutr Cancer. 1999; 33:188-95). Linum usitatissimum contains Linoleic acid, an EstrogenicReceptor ligand that can bind to estrogen receptors and inducecertain estrogen inducible genes (Liu J, Burdette J E, Sun Y.Isolation of linoleic acid as an estrogenic compound from thefruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine.2004; 11: 18-23). The seeds of Linum contain 117 active principles.
Pueraria lobata (Kudzu): the active components in kudzu root arethe isoflavones puerarin, daidzin, genistin, daidzein, andgenistein. Pueraria lobata has high estrogenic relative potency(Kang S C, Lee C M, Choi H. Evaluation of oriental medicinal herbsfor estrogenic and antiproliferative activities. Phytother Res.Advance Epub 2006, Aug. 14). A clinical trial of a nutritionalsupplement containing isoflavones from kudzu and red clover, alongwith other targeted nutrients on menopausal symptoms and markers ofbreast cancer and CVD risk, carried out in twenty-five menopausalwomen suffering from severe hot flushes and night sweats showed a46% decrease in reported hot flushes. Quality of life showedsimilar improvement. The results of this trial suggests that thiscombination isoflavone nutritional supplement may significantlyrelieve the most troubling symptoms of menopause, as well as confersome chemopreventive and cardioprotective benefits (Lukaczer D,Darland G, Tripp M. Clinical effects of a proprietary combinationisoflavone nutritional supplement in menopausal women: a pilottrial. Altern Ther Health Med. 2005; 11:60-5). Estrogenic activityof the Chinese herb kudzu root was investigated by a recombinantyeast screening assay (YES). The crude extract and itssub-fractions, showed clear estrogenic activity. The results showedthat the high content of isoflavones as well as the high estrogenicactivity could make kudzu root extract an interesting candidate forhormone replacement therapy (Zhang Y, Chen J, Zhang C. Analysis ofthe estrogenic components in kudzu root by bioassay and highperformance liquid chromatography. J Steroid Biochem Mol. Biol.2005; 94: 375-81). Pueraria lobata showed estrogenic activity whichexplains its reported efficacy for the treatment of menopausalsymptoms (Zhang C Z, Wang S X, Zhang Y. In vitro estrogenicactivities of Chinese medicinal plants traditionally used for themanagement of menopausal symptoms. J. Ethnopharmacol. 2005; 98:295-300). Puerariae radix has effective estrogenic actions andcould be developed as estrogenic supplement (Kim O S, Choi J H,Soung Y H. Establishment of in vitro test system for the evaluationof the estrogenic activities of natural products. Arch Pharm Res.2004; 27: 906-11). Results of another showed that puerarin andtotal pueraria isoflavones acted as weak estrogen-like effect onestrogen-deficiency animals, while no effect on normal-estrogenlevel ones, but as antiestrogen-like effect in high-estrogen-levelones. Results suggested that puerarin and TIP possessed property ofpartial agonist of estrogen receptor (Zheng G, Zhang X, Zheng J.Estrogen-like effects of puerarin and total isoflavones fromPueraria lobata. Zhong Yao Cai. 2002; 25: 566-8). Puirura containsat least 26 active principles.
Serenoa repens (Saw palmetto, Sabal serrulata, Scrub-Palmetto). Itsmain active principles are saturated fatty acids: lauric, myristic,palmitic, capric, caprylic; and unsaturated fatty acids: oleic,linoleic and linolenic. These fatty acids have demonstratedinhibiting action on 5-Alpha-Reductase, enzyme which transformsTestosterone into Dihydrotestosterone (Raynaud J P, Cousse H,Martin P M. Inhibition of type 1 and type 2 5alpha-reductaseactivity by free fatty acids, active ingredients of Permixon. JSteroid Biochem Mol. Biol. 2002; 82: 233-9). Estrogens aremanufactured from androstenedione or testosterone as immediateprecursors. When the Testosterone into Dihydrotestosteronetransformation is inhibited, Testosterone levels are improved;which is used in the biosynthesis of estrone, estradiol andestriol, deficient hormones during menopause. Serenoa repenscontains Linoleic acid, an Estrogenic Receptor ligand that can bindto estrogen receptors and induce certain estrogen inducible genes(Liu J, Burdette J E, Sun Y. Isolation of linoleic acid as anestrogenic compound from the fruits of Vitex agnus-castus L.(chaste-berry). Phytomedicine. 2004; 11: 18-23). Serenoa contains13 active principles.
Tribulus terrestris (Puncture Vine, Caltrop, Yellow Vine, bindyeye, bindii, bullhead, burnut, burra gokhroo, caltrop, calthrops,cat's head, common dubbeltjie, devil's thorn, devil's weed,doublegee, dubbeltje, goathead, gokshura, Maltese cross, Mexicansandbur, puncture vine, puncture weed, rose, small caltrops,tackweed, Texas sandbur, yellow vine and Goathead). The fruits androots of Tribulus contain active principles such as: phytosterols,flavonoids, alkaloids, glucosides and steroidal saponins of thefurostanol sub-class with a predominant amount of protodioscine (noless than 45%) which seems to be the principle that produces theclinical results. These active principles exert an effectivestimulant effect over the reproductive systems, with the increasein body mass, vigour and resistance. Protodioscin is aphytochemical agent derived from Tribulus terrestris plant that isconverted by the supra renal glands into DHEA[De-Hydro-Epi-Androsterone] (Adimoelja A. Phytochemicals and thebreakthrough of traditional herbs in the management of sexualdysfunctions. Int J. Androl. 2000; 23: 82-4) constituting the rawmaterial for the production of testosterona and estrogens, as wellas other hormones. DHEA production declines with age. When theorganism reaches 60 years it produces only between 5 and 15% of thenormal amount, thus contributing to the ageing process. DHEA istransformed into Androstenedione and Testosterone, and later intoEstrone and Estradiol, hormones which are lacking during menopause.Results of various studies sugest that DHEA supplements improve thesymptoms of menopause, libido and osteoporosis in women.Significantly increasing levels of estradiol, luteinizing (LH) andfolicule-stimulating hormone (FSH). This way Tribulus improves thereproductive functions in women. Tribulus contains 46 activeprinciples in a single therapeutic.
Vitamin E: From the Practice Guideline of the North AmericanMenopause Society "In women who need relief for mild vasomotorsymptoms, the North American Menopause Society recommends firstconsidering lifestyle changes, either alone or combined with anonprescription remedy, such as dietary isoflavones, black cohosh,or vitamin E" (italics by inventor) (Treatment ofmenopause-associated vasomotor symptoms: position statement of TheNorth American Menopause Society. Menopause. 2004; 11: 11-33). Formild symptoms that do not interfere with sleep or daily function,behavioral changes in conjunction with vitamin E (800 IU/d) use isa reasonable initial approach for the management of menopause(Shanafelt T D, Barton D L, Adjei A A. Pathophysiology andtreatment of hot flash).
Claim 1 of 2 Claims
1. A phytoceutical composition comprising: 27 mg of Ajugaturkestanica, 82 mg of Panax quinquefolius, 82 mg of Pfaffiapaniculata, 11 mg of Rhapontium carthamoides, 27 mg of Araliamandshurica, 27 mg of Astragalus membranaceus, 27 mg of Polygonummultiflorum, 82 mg of Vitex agnus castus, 82 mg of Angelicasinensis, 82 mg of Cimicifuga racemosa, 82 mg of Dioscorea villosa,82 mg of Linum usitatissimum, 82 mg of Pueraria lobata, 27 mg ofSerenoa repens, 82 mg of Tribulus terrestris and 16 mg of Vitamin Etogether with pharmaceutically acceptable excipients.
A Phytoceutical composition for the prevention and treatment ofmenopause disorders and symptoms is provided. A specificcombination of extracts of plants is taught, as well as principlesfor varying the formulations based on categorizing plants into oneof three groups, Energy, Bio-Intelligence, and Organization andselecting several plants from each group. Such combinations havesynergistic effects, with minimal side effects.
Description of the Invention
SUMMARY OF THE INVENTION
A number of known beneficial plants were classified according totheir capacity to enhance the three main elements that supportoverall health: Energy (E), Bio-intelligence (I) and Organization(O). A synergistic effect is expected when all three categories ofherbs (E, I, O) are included in a formulation, preferably at leasttwo or three or four plants from each category. Thus, oneembodiment of the invention provides a method of selectingadditional disease treating formulations according to theseprinciples. An example of a formulation prepared this way isprovided and additional formulations are being prepared and tested.As they reach menopause, a majority of women living in Westernizedcountries experience climacteric symptoms. The climacteric syndromeinvolves a variety of symptoms such as profuse sweating, insomnia,memory loss, decreased sexual drives, joint aches, and anxiety.However, amongst these symptoms, hot flashes and sweats aregenerally considered the hallmark and result in the majority of themedical consultations for this condition. Hormone replacementtherapy (HRT) has been used to remediate these symptoms. Recentstudies, however, have suggested that HRT may increase the risk ofdeveloping breast cancer and cardiovascular disease (CVD). Sinceancient times, extracts of plants have been used for women's healthto prevent menopausal symptoms. Therefore, many women are lookingfor alternative treatment options. Thus, another embodiment of theinvention provides an effective, natural composition for treatingmenopause disorders and symptoms. The composition can be usedalone, or can be combined with simultaneous use of one or morepharmaceutical compositions.
DETAILED DESCRIPTION OF THE INVENTION
"Pharmaceutically acceptable excipients" is used hereinaccording to art accepted meanings, and includes those ingredientsneeded to formulate a medicine for mammalian use, including the useof gelatin capsules.
"Synergistic" or "synergy" is used herein tomean that the effect is more than its additive property. Inpreferred embodiments, the synergy is at least 1.2, 1.5, 2,5, or 10fold.
By use of "plants," what is meant herein is that theplant (or that portion with medicinal activity) is used whole,ground, or as an extract. Also included are purified activeingredients and derivatives thereof. However, it is believed thatthe best efficacy of plants used herein is achieved with the use ofthe entire plant or its extracts, rather than with the use ofisolated active ingredients.
Further, although plants are named here according to commonly usednomenclature, with improving taxonomy plants are oftenreclassified. Whenever a plant is referenced, it includes relatedspecies with similar active ingredients.
The following examples are illustrative only and should not serveto unduly limit the invention.
EXAMPLE 1
Plant Characteristics
Menopause Disorder and Symptoms
Energy Enhancing Phytoceuticals
Ajuga turkestanica: Its main active principle turkesterone, aphytoecdysteroid possessing an 11alpha-hydroxyl group. Ecdysteroidsnormalize NADH dehydrogenase activity, enzyme which catalyzeselectron transfer from NADH to ubiquinones in the oxidativephosphorylation processes which occur at the mitochondrial level,contributing to the potential electrochemical buildup required toproduce ATP. It also normalizes the succinate dehydrogenase enzymewhich participates in the tricarboxilic acid cycle, whichtranslates to ATP synthesis and patient energy level increases[Tashmukhamedova M A, Almatov K T, Syrov V N. Comparative study ofthe effect of ecdysterone, turkesterone and nerobol on the functionof rat liver mitochondria in experimental diabetes. Vopr Med. Khim.1986; 32:24-8].
Panax quinquefolius (American Ginseng, Anchi, Canadian Ginseng,Five Fingers, Ginseng, American, North American Ginseng, Red Berry,Ren Shen, and Tienchi) is related to Panax ginseng, but is adistinct species with higher levels of ginsenoside Rb1 and withoutginsenoside Rf. These substances confer energizing propertiesbecause they increase ATP synthesis. It also has antioxidant andanti-inflammatory effects. Results of clinical research studiesdemonstrate that Panax quinquefolius improves physical and mentalperformance and increases resistance to exogenous stress factors.The incorporation of this phytomedicine provides at least 206active principles in a single therapeutic.
Pfaffia paniculata (Suma, Brazilian Ginseng, Pfaffia, Para Tudo,Corango-acu; also Hebanthe paniculata, Gomphrena paniculata, G.eriantha, Iresine erianthos, I. paniculata, I. tenuis, P. eriantha,Xeraea paniculata) contains active glycosides (beta-ecdysone andthree ecdysteroids), six different pfaffic acids, phytosterols(sitosterol and estigmasterol). Pfaffia also contains saponins and19 different amino acids, minerals, vitamins and pantoneic acid.Its germanium content probably accounts for its properties as anoxygenator at the cellular level, and its high iron content mayaccount for its traditional use for anemia. This herb increasesenergy through an increase in ATP synthesis and oxygenation at thecellular level, and it also has anabolic activity at the muscularlevel. These substances act as hormone precursors modulatingestrogen, progesterone and testosterone production (Oshima M, Gu Y.Pfaffia paniculata-induced changes in plasma estradiol-17beta,progesterone and testosterone levels in mice. J Reprod Dev. 2003;49: 175-80) and have demonstrated effectivity in the management ofdiverse conditions related to hormone unbalance such as menopause(Pitchford, Paul. Healing With Whole Foods: Asian Traditions andModern Nutrition. North Atlantic Books; 3rd Edition; 2002. ISBN:1556434308). Suma has safe estrogenic activity because of its storeof sitosterol, a compound which increases body's natural estrogen.Incorporation of Pfaffia provides 44 active principles.
Rhaponticum carthamoides (Leuzea, or Maral Root) contains a mixtureof compounds called `levseins`. Levseins represents a complex ofmore than 10 ecdysterones including 20-beta-ecdysterone,makisterone C, 24-dehydromakisterone A, carthamosterone, polypodyneB and ajugasterone C. Ecdysteroids normalize NADH dehydrogenaseactivity, enzyme which catalizes NADH electron transfer to theubiquinone in the oxidative phosphorylation processes at themitochondrial level, contributing to buildup the electrochemicalpotential used to produce ATP. It also normalizes the succinatedehydrogenase activity, enzyme which acts in the tricarboxilic acidcycle, which translates in ATP synthesis and patient energy levelincreases. In women with low levels of estrogens, Ecdysteronebehaves as an anabolic steroid mimicking the effects of thesehormones. Incorporation of this phytomedicine in a compositionprovides at least 10 active principles in a single therapeutic.
Bio-Intelligence Modulators
Aralia mandshurica (Manchurian Thorn Tree) The main activeprinciples are triterpene saponins aralosides (elatosides).Siberians traditionally preferred Aralia for immune health, toreduce stress/depression, and to improve physical and mentalperformance. Siberians would often combine Aralia with otheradaptogens for maximal stress reduction/performance enhancementbenefits. Aralia extract was included in the official RussianPharmacopoeia in 1983 as a treatment for the symptoms of stressoverload, such as fatigue, weakness, headache, libido loss,depression, immune weakness, etc. G. P. Gubina reported in 1988 a90 percent success rate--using Aralia--in 106 patients treated forvarious "asthenic" (stress overload/weakness) conditions.Aralia enhances a person's ability for memorization and prolongedconcentration. In proofreading tests, after taking this plant, adecrease in the quantity of mistakes was observed in 88 percent ofthe experimental group, while an increase in the quantity ofmistakes was observed in 54 percent of the control group. Thosetaking Aralia mandshurica exerted a strong stimulating influenceamong test subjects who displayed a great improvement in readingcomprehension, aptitude and speed. [A. A. Lebedev/Far EastScientific Center of the USSR]; [V. V. Kazakevich/Academy ofSciences, Vladivostok, Russia].
Astragalus membranaceus (Huang-Qi, Huangqi) This plant containsthree main types of active principles. Isoflavones, principalmenteFormononetin, astragalans, and astragalosides which act asmodulators of the hypothalamus-hypofisis-adrenal axis response. Italso contains linoleic acid. Formononetin has Estrogenic Receptoralpha and beta binding affinity (Halabalaki M, Alexi X, AligiannisN. Estrogenic activity of isoflavonoids from Onobrychis ebenoides.Planta Med. 2006; 72: 488-93). Dietary supplements are currentlyused to treat menopausal symptoms because of their high content ofthe mildly estrogenic isoflavones (formononetin). This compound isestrogenic in vitro and in vivo (Booth N L, Overk C R, Yao P.Seasonal variation of red clover (Trifolium pratense L., Fabaceae)isoflavones and estrogenic activity. J Agric Food Chem. 2006; 54:1277-82).
Isoflavones have a high affinity to estrogen receptor alpha(ERalpha), estrogen receptor beta (ERbeta), progesterone receptor(PR) and androgen receptor (AR). The affinity to ER has been usedas an explanation of the effects of isoflavones in the treatment ofmenopausal disorders. Biochemical analysis shows thatphytoestrogens have multiple actions beside selective estrogenreceptor modulator (SERM)-activity. They act as selective estrogenenzyme modulators (SEEMs), have antioxidant activity and interactwith transcription factors such as NF-kappaB. Furthermore, it isindicated that they have protective effects on osteoporosis and thecardiovascular system (Beck V, Rohr U, Jungbauer A. Phytoestrogensderived from red clover: an alternative to estrogen replacementtherapy? J Steroid Biochem Mol. Biol. 2005; 94: 499-518).Formononetin showed clear estrogenic activity through estrogenreceptor alpha (ERalpha) and estrogen receptor beta (ERbeta) andaffinity to progesterone (PR) and androgen (AR) receptors. In vitroassays and chemical analysis showed that theoretical estrogenicactivity expressed as equivalent E2 concentration is in the samerange as recommended for synthetic estrogens. Broader spectrum ofaction and hypothesized lower side effects by action through ERbetamake them suitable for alternative hormone replacement therapy(Beck V, Unterrieder E, Krenn L. Comparison of hormonal activity(estrogen, androgen and progestin) of standardized plant extractsfor large scale use in hormone replacement therapy. J SteroidBiochem Mol. Biol. 2003; 84: 259-68). Formononetin binds well tohuman ER beta and human ER alpha (Morito K, Aomori T, Hirose T.Interaction of phytoestrogens with estrogen receptors alpha andbeta (II). Biol Pharm Bull. 2002; 25: 48-52). Astragalus offers 38active principles in a single therapeutic.
Polygonum multiflorum (Fo-Ti, Chinese Knotweed, Chinese Cornbind,Climbing Knotweed, Flowery Knotweed, Fleeceflower, He Shou Wu) Themain constituents of Polygonum multiflorum are: emodin,chrysophanol, rhein, 6-OH-emodin, emodin-8-beta-D-glucoside,polygonimitin B,2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside, gallic acid.This pkant has been used traditionally in China for menopausesymptoms management. Polygonum has estrogenic activity (Kang S C,Lee C M, Choi H. Evaluation of oriental medicinal herbs forestrogenic and antiproliferative activities. Phytother Res. 2006Aug. 14). Another study which gives support to the reportedefficacy of Chinese medicines used for hormone replacement therapyis Zhang C Z, Wang S X, Zhang Y. In vitro estrogenic activities ofChinese medicinal plants traditionally used for the management ofmenopausal symptoms. J. Ethnopharmacol. 2005; 98: 295-300).Polygonum provides 47 active principles in a single therapeutic.
Vitex agnus castus (Chasteberry, Chaste-Tree): From the fruit ofthis plant are obtained an essential oil, linoleic acid, twoiridoid glicosides (aucubine y el agnusine); a flavone (casticin),flavonoids derived from kaempferol and quercetagine and otherflavonoids such as penduletin, vitexin and apigenin. Penduletin andapigenin, flavonoids of Vitex agnus castus are estrogeniccompounds. Both substances are specific ligands for thebeta-estrogenic receptor (Jarry H, Spengler B, Wuttke W. In vitroassays for bioactivity-guided isolation of endocrine activecompounds in Vitex agnus-castus. Maturitas. Epub Aug. 21, 2006).Extracts of Vitex agnus-castus displace estradiol from EstrogenicReceptor alpha and beta. Linoleic acid is one possible estrogeniccomponent of the extract. Linoleic acid is an Estrogenic Receptorligand. These data suggest that linoleic acid from the fruits ofVitex agnus-castus can bind to estrogen receptors and inducecertain estrogen inducible genes (Liu J, Burdette J E, Sun Y.Isolation of linoleic acid as an estrogenic compound from thefruits of Vitex agnus-castus L (chaste-berry). Phytomedicine. 2004;11: 18-23). A clinical trial on 23 menopausal patients withessential oils of Vitex agnus castus indicated strong symptomaticrelief of common menopausal symptoms. A second clinical trial on 52additional subjects appears to support the finding of the firsttrial (Chopin Lucks B. Vitex agnus castus essential oil andmenopausal balance: a research update Complement Ther NursMidwifery. 2003; 9: 157-60). Essential oils from Vitex agnus castuswere found to be effective, in menopausal balance (Lucks B C,Sorensen J, Veal L. Vitexagnus-castus essential oil and menopausalbalance: a self-care survey. Complement Ther Nurs Midwifery. 2002;8: 148-54). Vitex agnus preparations are commonly used for thetreatment of menopausal symptoms.
Organizational Improvers
Angelica sinensis (Dong quai or Angelica, also Angelicaarchangelia, Angelica pubescens and Angelica sylvestris Can qui,Angelica china, dangdanggui, dang gui, dong quai, duong qui,handanggui, hashyshat almalak, kara toki, langdu danggui, min-gui,tang-kuei, tangkuei, ta{grave over ( )}n q ui) Contains terpenes(terpenes, mainly .beta.-phellandrene, with .beta.-bisabolene,.beta.-caryophyllene, .beta.-phellandrene, .alpha.- and.beta.-pinene, limonene, linalool, borneol, acetaldehyde,menthadienes and nitromenthadienes), macrocyclic lactones(including tridecanolide, 12-methyl tridecanolide,pentadecanolide), phthalates (such as hexamethylphthalate),coumarins (especially furocoumarin glycosides such as marmesin andapterin), angelicin and byakangelicin derivatives (osthol,umbelliferone, psoralen, bergapten, imperatoren, xanthotoxol,xanthotoxin, oxypeucedanin and more), as well as various sugars,plant acids, flavonoids, and sterols. It also, contains alkylphthalides (Ligustilide); terpenes, phenylpropanoids (ferulic acid)and benzenoids. The results of a study demonstrated the estrogenicnature of the extract of Angelica (Circosta C, Pasquale R D,Palumbo D R. Estrogenic activity of standardized extract ofAngelica sinensis. Phytother Res. 2006; 20: 665-9). Aplacebo-controlled trial on 55 postmenopausal women who complainedof hot flushes and refused hormonal therapy showed a significantdifference between the study group and the control group in thedecrease in number and intensity of hot flushes from baseline tocompletion of treatment. There was also a marked alleviation ofsleep disturbances and fatigue (Kupfersztain C, Rotem C, Fagot R.The immediate effect of natural plant extract, Angelica sinensisand Matricaria chamomilla (Climex) for the treatment of hot flushesduring menopause. A preliminary report. Clin Exp Obstet Gynecol.2003; 30: 203-6). Dong quai showed weak Estrogen Receptor bindingand Progesteron Receptor and pS2 mRNA induction. These data suggesta potential use in the treatment of menopausal symptoms (Liu J,Burdette J E, Xu H. Evaluation of estrogenic activity of plantextracts for the potential treatment of menopausal symptoms. JAgric Food Chem. 2001; 49: 2472-9). Angelica provides 70 activeprinciples.
Cimicifuga racemosa (Black Cohosh, Black Snakeroot): Key activeconstituents are: triterpene glycosides (containing a cyclopropanering) including acetein, cimicifugoside and racemoside; isoflavonesincluding formononetin; aromatic acids including isoferulic acidand salicylic acid. Also tannin, resin (cimicifugin), ranunculin,fatty acids, starch and sugars. A multicenter, randomized,placebo-controlled, double-blind, parallel group study wasconducted in 122 menopausal women. The results indicate asuperiority of Cimicifuga racemosa extract compared to placebo inpatients with menopausal disorders (Frei-Kleiner S, Schaffner W,Rahlfs V W. Cimicifuga racemosa dried ethanolic extract inmenopausal disorders: a double-blind placebo-controlled clinicaltrial. Maturitas. 2005; 51: 397-404). A clinical trial studied thechanges in subjective symptoms of menopause in 2016 women treatedwith an extract of Cimicifuga racemosa. The most favorable changeswere found in hot flashes, sweating, insomnia, and anxiety. Theextract of C. racemosa was found to be effective in the alleviationof menopausal symptoms (Vermes G, Banhidy F, Acs N. The effects ofremifemin on subjective symptoms of menopause. Adv Ther. 2005; 22:148-54). In a randomized clinical controlled study on climactericcomplaints, the extract of Cimicifuga racemosa significantlyreduced the number of hot flushes per day and vasomotor symptoms.CONCLUSIONS: CR may be a valid alternative in the management ofclimacteric complaints in those women who cannot be treated with orjust refuse conventional strategies (Nappi R E, Malavasi B, BrunduB. Efficacy of Cimicifuga racemosa on climacteric complaints: arandomized study versus low-dose transdermal estradiol. GynecolEndocrinol. 2005; 20: 30-5). Black cohosh has been used in the USfor over 100 years. Review of the published clinical data suggeststhat cimicifuga may be useful for the treatment of menopausalsymptoms, such as hot flashes, profuse sweating, insomnia, andanxiety (Mahady G B. Black cohosh (Actaea/Cimicifuga racemosa):review of the clinical data for safety and efficacy in menopausalsymptoms. Treat Endocrinol. 2005; 4: 177-84). Osmers R, Friede M,Liske E. Efficacy and safety of isopropanolic black cohosh extractfor climacteric symptoms. Obstet. Gynecol. 2005; 105: 1074-83. Thisrandomized, multicenter, double-blind clinical trial compared theefficacy and tolerability of the black cohosh extract in thetreatment of climacteric complaints compared with placebo in atotal of 304 patients. The results showed that the black cohoshextract was more effective than placebo and clinically relevant.Cimicifuga contains at least 45 active principles in a singletherapeutic.
Dioscorea villosa (Mexican wild yam, china root, colic root,rheumatism root, huesos del diablo, yuma.) contains steroidsapogenins (dioscine, dioscorin and diosgenine) as the main activeprinciples. It also contains salts and minerals, such as: aluminum,calcium, chrome, cobalt, iron, selenium, silica, sodium, tin, zinc,magnesium, manganese, phosphorus and potassium; and vitamins:ascorbic acid, beta-carotene, niacin, riboflavin and thiamine.Diosgenine can be transformed into pregnenolone, and progesterone[Gareth, Thomas. Medicinal Chemistry. John Wiley & Sons; Firstedition December 2000. ISBN: 0471489352]. The starting material forthe production of progesterone is diosgenin obtained from a numberof Dioscorea species (a plant source). Diosgenin may be convertedto pregnenolone acetate by a series of steps. Wild yam is used as aprecursor in the manufacture of "natural progesterones".Natural progesterone products help reduce hot flashes or improvevaginal health [Tagliaferri, Mary. The New Menopause Book. AveryPublisher; March, 2006]. A clinical controlled trial in 24postmenopausal women showed that Dioscorea significantly increasesserum concentrations of estrone, sex hormone binding globulin, andestradiol. Although the exact mechanism is not clear, Dioscoreaimproves the status of sex hormones (Wu W H, Liu L Y, Chung C J.Estrogenic effect of yam ingestion in healthy postmenopausal women.J Am Coll Nutr. 2005; 24: 235-43). The incorporation of thisphytomedicine provides at least 29 active principles in a singletherapeutic.
Linum usitatissimum (Flaxseed, Flax, Linseed) Phytoestrogens arediphenolic compounds that are present in several plants eaten byhuman beings. Flaxseed is particularly abundant source ofphytoestrogens. Phytoestrogens have been shown to have significantestrogen agonists/antagonists effects in animals and humans. Thereis epidemiological, laboratory and clinical evidence whichindicates that phytoestrogens, like certain selective estrogenreceptor modulators, have a positive effect on the lipoproteinprofile and bone density. They might also improve some of theclimacteric symptoms. (Brzezinski A, Debi A. Phytoestrogens: the"natural" selective estrogen receptor modulators? Eur JObstet Gynecol Reprod Biol. 1999; 85: 47-51). Phytoestrogens, whichare abundant in flaxseed, have chemical structures resembling thoseof endogenous estrogens and have been shown to exert hormonaleffects. A clinical, randomized, controlled trial in 46postmenopausal women supplemented with either a placebo, soy, orflaxseed for 16 wk showed that urinary concentrations of2-hydroxyestrone increased significantly in the flaxseed group. Inthe soy and placebo groups, no significant correlation wasobserved. CONCLUSIONS: Supplementation with flaxseed modifiesurinary estrogen metabolite excretion to a greater extent than doessupplementation with an equal amount of soy (Brooks J D, Ward W E,Lewis J E. Supplementation with flaxseed alters estrogen metabolismin postmenopausal women to a greater extent than doessupplementation with an equal amount of soy. Am J Clin Nutr. 2004;79: 318-25). A clinical, randomized, controlled trial showed thatFlaxseed is as effective as oral estrogen-progesterone to improvemild menopausal symptoms. (Lemay A, Dodin S, Kadri N. Flaxseeddietary supplement versus hormone replacement therapy inhypercholesterolemic menopausal women. Obstet. Gynecol. 2002; 100:495-504). A clinical, randomized, controlled trial examined theeffects of flaxseed consumption on urinary estrogen metaboliteexcretion in 28 postmenopausal women showed that Flaxseedsupplementation significantly increased urinary 2-OHEstrogenexcretion and the urinary 2/16 alpha-OHE1 ratio. Results suggestprotective effects in postmenopausal women (Haggans C J, Hutchins AM, Olson B A. Effect of flaxseed consumption on urinary estrogenmetabolites in postmenopausal women. Nutr Cancer. 1999; 33:188-95). Linum usitatissimum contains Linoleic acid, an EstrogenicReceptor ligand that can bind to estrogen receptors and inducecertain estrogen inducible genes (Liu J, Burdette J E, Sun Y.Isolation of linoleic acid as an estrogenic compound from thefruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine.2004; 11: 18-23). The seeds of Linum contain 117 active principles.
Pueraria lobata (Kudzu): the active components in kudzu root arethe isoflavones puerarin, daidzin, genistin, daidzein, andgenistein. Pueraria lobata has high estrogenic relative potency(Kang S C, Lee C M, Choi H. Evaluation of oriental medicinal herbsfor estrogenic and antiproliferative activities. Phytother Res.Advance Epub 2006, Aug. 14). A clinical trial of a nutritionalsupplement containing isoflavones from kudzu and red clover, alongwith other targeted nutrients on menopausal symptoms and markers ofbreast cancer and CVD risk, carried out in twenty-five menopausalwomen suffering from severe hot flushes and night sweats showed a46% decrease in reported hot flushes. Quality of life showedsimilar improvement. The results of this trial suggests that thiscombination isoflavone nutritional supplement may significantlyrelieve the most troubling symptoms of menopause, as well as confersome chemopreventive and cardioprotective benefits (Lukaczer D,Darland G, Tripp M. Clinical effects of a proprietary combinationisoflavone nutritional supplement in menopausal women: a pilottrial. Altern Ther Health Med. 2005; 11:60-5). Estrogenic activityof the Chinese herb kudzu root was investigated by a recombinantyeast screening assay (YES). The crude extract and itssub-fractions, showed clear estrogenic activity. The results showedthat the high content of isoflavones as well as the high estrogenicactivity could make kudzu root extract an interesting candidate forhormone replacement therapy (Zhang Y, Chen J, Zhang C. Analysis ofthe estrogenic components in kudzu root by bioassay and highperformance liquid chromatography. J Steroid Biochem Mol. Biol.2005; 94: 375-81). Pueraria lobata showed estrogenic activity whichexplains its reported efficacy for the treatment of menopausalsymptoms (Zhang C Z, Wang S X, Zhang Y. In vitro estrogenicactivities of Chinese medicinal plants traditionally used for themanagement of menopausal symptoms. J. Ethnopharmacol. 2005; 98:295-300). Puerariae radix has effective estrogenic actions andcould be developed as estrogenic supplement (Kim O S, Choi J H,Soung Y H. Establishment of in vitro test system for the evaluationof the estrogenic activities of natural products. Arch Pharm Res.2004; 27: 906-11). Results of another showed that puerarin andtotal pueraria isoflavones acted as weak estrogen-like effect onestrogen-deficiency animals, while no effect on normal-estrogenlevel ones, but as antiestrogen-like effect in high-estrogen-levelones. Results suggested that puerarin and TIP possessed property ofpartial agonist of estrogen receptor (Zheng G, Zhang X, Zheng J.Estrogen-like effects of puerarin and total isoflavones fromPueraria lobata. Zhong Yao Cai. 2002; 25: 566-8). Puirura containsat least 26 active principles.
Serenoa repens (Saw palmetto, Sabal serrulata, Scrub-Palmetto). Itsmain active principles are saturated fatty acids: lauric, myristic,palmitic, capric, caprylic; and unsaturated fatty acids: oleic,linoleic and linolenic. These fatty acids have demonstratedinhibiting action on 5-Alpha-Reductase, enzyme which transformsTestosterone into Dihydrotestosterone (Raynaud J P, Cousse H,Martin P M. Inhibition of type 1 and type 2 5alpha-reductaseactivity by free fatty acids, active ingredients of Permixon. JSteroid Biochem Mol. Biol. 2002; 82: 233-9). Estrogens aremanufactured from androstenedione or testosterone as immediateprecursors. When the Testosterone into Dihydrotestosteronetransformation is inhibited, Testosterone levels are improved;which is used in the biosynthesis of estrone, estradiol andestriol, deficient hormones during menopause. Serenoa repenscontains Linoleic acid, an Estrogenic Receptor ligand that can bindto estrogen receptors and induce certain estrogen inducible genes(Liu J, Burdette J E, Sun Y. Isolation of linoleic acid as anestrogenic compound from the fruits of Vitex agnus-castus L.(chaste-berry). Phytomedicine. 2004; 11: 18-23). Serenoa contains13 active principles.
Tribulus terrestris (Puncture Vine, Caltrop, Yellow Vine, bindyeye, bindii, bullhead, burnut, burra gokhroo, caltrop, calthrops,cat's head, common dubbeltjie, devil's thorn, devil's weed,doublegee, dubbeltje, goathead, gokshura, Maltese cross, Mexicansandbur, puncture vine, puncture weed, rose, small caltrops,tackweed, Texas sandbur, yellow vine and Goathead). The fruits androots of Tribulus contain active principles such as: phytosterols,flavonoids, alkaloids, glucosides and steroidal saponins of thefurostanol sub-class with a predominant amount of protodioscine (noless than 45%) which seems to be the principle that produces theclinical results. These active principles exert an effectivestimulant effect over the reproductive systems, with the increasein body mass, vigour and resistance. Protodioscin is aphytochemical agent derived from Tribulus terrestris plant that isconverted by the supra renal glands into DHEA[De-Hydro-Epi-Androsterone] (Adimoelja A. Phytochemicals and thebreakthrough of traditional herbs in the management of sexualdysfunctions. Int J. Androl. 2000; 23: 82-4) constituting the rawmaterial for the production of testosterona and estrogens, as wellas other hormones. DHEA production declines with age. When theorganism reaches 60 years it produces only between 5 and 15% of thenormal amount, thus contributing to the ageing process. DHEA istransformed into Androstenedione and Testosterone, and later intoEstrone and Estradiol, hormones which are lacking during menopause.Results of various studies sugest that DHEA supplements improve thesymptoms of menopause, libido and osteoporosis in women.Significantly increasing levels of estradiol, luteinizing (LH) andfolicule-stimulating hormone (FSH). This way Tribulus improves thereproductive functions in women. Tribulus contains 46 activeprinciples in a single therapeutic.
Vitamin E: From the Practice Guideline of the North AmericanMenopause Society "In women who need relief for mild vasomotorsymptoms, the North American Menopause Society recommends firstconsidering lifestyle changes, either alone or combined with anonprescription remedy, such as dietary isoflavones, black cohosh,or vitamin E" (italics by inventor) (Treatment ofmenopause-associated vasomotor symptoms: position statement of TheNorth American Menopause Society. Menopause. 2004; 11: 11-33). Formild symptoms that do not interfere with sleep or daily function,behavioral changes in conjunction with vitamin E (800 IU/d) use isa reasonable initial approach for the management of menopause(Shanafelt T D, Barton D L, Adjei A A. Pathophysiology andtreatment of hot flash).
Claim 1 of 2 Claims
1. A phytoceutical composition comprising: 27 mg of Ajugaturkestanica, 82 mg of Panax quinquefolius, 82 mg of Pfaffiapaniculata, 11 mg of Rhapontium carthamoides, 27 mg of Araliamandshurica, 27 mg of Astragalus membranaceus, 27 mg of Polygonummultiflorum, 82 mg of Vitex agnus castus, 82 mg of Angelicasinensis, 82 mg of Cimicifuga racemosa, 82 mg of Dioscorea villosa,82 mg of Linum usitatissimum, 82 mg of Pueraria lobata, 27 mg ofSerenoa repens, 82 mg of Tribulus terrestris and 16 mg of Vitamin Etogether with pharmaceutically acceptable excipients.
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