WO2018163209A1

WO2018163209A1 - Menopause supplement

Info

Publication number: WO2018163209A1
Application number: PCT/IN2018/050126
Authority: WO
Inventors: Greesh Kumar JUNEJA; Vijay Prakash; Rajendra Kanaiyalal SANGHAVI; Neelakshi Singh SHARMA
Original assignee: Big Brother Nutra Care Pvt Ltd
Current assignee: Big Brother Nutra Care Pvt Ltd
Priority date: 2017-03-10
Filing date: 2018-03-06
Publication date: 2018-09-13
Anticipated expiration: 2019-09-10
Also published as: WO2018163209A4

Abstract

This invention pertains to a single serve dosage composition for menopausal women effective for relieving hot flushes, cold sweats, strengthening bones, protection against free radicals responsible for causing cancer and skin wrinkling and other ageing changes, reducing long-term menopausal consequences and maintaining body contours, preservation of memory that could be disturbed by Alzheimer's disease, and adaptogenic benefit to facilitate both mood uplifting as well as enjoyable intimacy. The composition comprises, at least, following ingredients: (a) an extract of Angelica archangelica L. or alternatively, an extract of Angelica sinensis (Oliv.) Diels, (b) an extract of Withania somnifera(L.) Dunal, (c) an extract of Curcuma longa L., (d) an extract of Angelica archangelica L, (e) Soy isoflavones, (f) Calcium and (g) Vitamin D. The Soy isoflavonesin this composition comprise a concentrated extract standardized to provide isoflavones Genistin and Genistein 24%, Daidzin and Daidzein 24%.

Description

FIE L D O F INVE NTIO N

This invention relates to a supplement for menopausal women. Particularly the invention relates to a supplement for menopausal women, which primarily comprises phyto-estrogens derived from plants.

¾ BAC KG R OU ND O F T H E INV E NTIO N

Menopause is a transition between two phases of a woman ^'s life and occurs when a woman permanently stops menstruating (having periods). It is a natural part of aging and there are nearly 50 million menopausal women in India.

Menstruation stops because the ovaries in women discontinue the production of two 3ft, hormones, namely estrogen and progesterone, which have been otherwise responsible for the periodical monthly bleeding.

Peri-menopause is the 2-10 years stage since the age when the estrogen production begins diminishing, and lasts up to 1 year post the complete cessation of periods (menopause).

Post-menopause means the period following the onset of menopause when the periods 3¾ finally stop.

Menopause sets in between the ages of 45 to 60 years; however, in rural Indians it could set in earlier. One-fifth of women in India do experience menopause before the age of 41 years.

Due to menopause, a woman could have complaints such as fatigue / lack of energy, headache and backache, hot flushes, cold sweats, cold hands and feet, numbness and i†l tingling of fingers / toes, excitability and anxiety besides difficulty in sexual performance due to dryness of vagina.

30% of Indian menopausal females have pertinent complaints vis-^~-vis 80% of women experiencing the same overseas. On account of menopause there are many other disturbing consequences such as urinary leakage and inability to control its flow (incontinence), thinning and wrinkling of skin, breast changes, brittle bones, increased risk of heart disease, and even memory disturbances with higher risk of developing Alzheimer^'s disease.

¾ The ovaries fail to produce estrogens and this is the prime reason for menopause and the changes due to itHence, taking estrogens is the logical answer to all the menopause-related concerns. Although estrogens are beneficial for the menopausal women, they are not advocated by healthcare professionals for their unrestricted use due to their potential to increase risk of causing cancers of breast and uterusfP rentice R L. P ostmenopausal ft, Hormone T herapy and the R isks of C oronary Heart Disease, Breast Cancer, and S troke.

S eminR eprod Med 2014; 32(8): 419-426; C hlebowski RT and Anderson G L. Menopausal Hormone Therapy and Cancer: C hanging C linical Observations of Target S ite S pecificity. Steroids 2014; 90: 53-59]. Natural estrogens that are derived from plants (phytoestrogens) serve the same purpose as their synthetic counterpart without causing an alarming risk of ¾ cancers of breast and uterus [P oluzzi E , P iccinni C and De P onti F. P hytoestrogens in Postmenopause: The State of the Art from a C hemical, P harmacological and R egulatory Perspective. C urr Med C hem 2014; 21 (4): 417-438].

The effects of estrogens are consequent to their binding with receptors called estrogen receptors (E R). Unless the estrogen sits inside the receptor there can be no effect; this is &\ similar to having a key requiring to be inserted into a matching slot if a lock has to be opened. In the body, the E Rs are of two types: alpha ( ) and beta ( ). T he E R are situated primarily in breast and uterus whilst the E R <f are available in the bone, brain, bladder (urinary), blood vessels and skin.

The hormone replacement therapy or hormone therapy (HT) with estrogens can bind with both E R as well as E R and this is responsible for beneficial action but also causing higher risk of cancer of breast and uterus (wherein the E R are primarily present). Isoflavones, the prime phytoestrogen, are derived best from soybeans. T he active isoflavones (genistein and daidzein) predominantly bind with E R <f and hence, are relatively free from associated cancer concerns since the E R are not targeted [Alekel D L, G ensche IU and Kurzer MS . S oy Isoflavones for R educing Bone Loss (S IR B L) S tudy: Effect of a ¾ three-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women. Menopause 2015; 22(2): 185-197].

S oy isoflavones reduce [C hen M-N, Lin C -C and Liu C-F. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. C limacteric 2015; 18(2): 260-269]: ft, e Hot flushes

e C old sweats

e C old hands and feet

e R isk of frail bones

e Narrowing of blood vessels

¾ e R epeated infections of urine

eVaginal dryness

eS kin changes like wrinkles

During menopause, 62% of women have cognitive decline, which manifests as difficulty &\ recalling words or numbers, needing memory aids, and forgetting why one was involved in a certain behavior(Daniel J M, Witty C F and R odgers S P. Long-term consequences of estrogens administered in midlife on female cognitive aging. HormBehav 2015; 74: 77-85). Another problematic symptom that likely hinders both peri- and post-menopausal women^'s ability to store and process information effectively is an increase in depressive symptomatology. The prevalence rate of depression ranges from 12% to 36% percent among peri- and post-menopausal women [S liwinski J R, J ohnson AK and E lkins G R. Memory Decline in P eri- and Post-menopausal Women: The Potential of Mind^' Body Medicine to Improve C ognitive P erformance. Integr Med Insights 2014; 9: 17-23].

Calcium is commonly given and consumed during the middle age and thereafter years for preventing weak bones especially due to menopause. However, calcium alone (and vitamin

¾ D that is commonly given together) has a poor assurance of reducing the fracture risk rate of bones. In 26 randomized controlled trials, calcium supplements reduced the risk of total fracture by 1 1 % and vertebral fracture by 14% but had no effect on forearm or hip fracture. The results, however, were even not consistent [Bolland MJ , Leung W, Tai V, Bastin S , G amble G D, G rey A and R eid IR . Calcium Intake and R isk of Fracture: Systematic R eview.

3 British Medical J ournal 2015; 351 doi: https://doi.org/10.1 136/bmj.h4580 (P ublished 29 S eptember 2015)]. Vitamin K2 MK7 as a supplement during menopause synergizes with calcium (and vitamin D) for assuring deposition of this mineral into the bones.

Bone is composed of a hard outer shell of calcium (primarily) and other minerals and a spongy matrix of inner tissues and is a living substance. T he entire skeleton s calcium

¾ content is replaced every 7 to 10 years. During the skeleton s remodeling, the body releases calcium from the bone into the bloodstream and this is caused by osteoclasts - cells that break down the skeleton; osteoblasts - cells that build up the skeleton compensate for the loss of bone calcium by facilitating deposition of calcium into the bones. As long as the bone- forming activity (by osteoblasts) is greater than the breakdown of bone (by osteoclasts), the

1&\ process of maintaining a healthy bone structure is maintained [Maresz K. P roper Calcium Use: Vitamin K2 as a P romoter of Bone and Cardiovascular Health. Integr Med (E ncinitas) 2015; 14(1 ): 34^"39].

Osteoblasts produce osteocalcin, which helps take calcium from the blood circulation and bind it to the bone matrix. In part, osteocalcin influences bone mineralization through its ability to bind to the mineral component of bone, hydroxyapatite, which in turn makes the skeleton stronger and less susceptible to fracture [Maresz K. P roper C alcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integr Med (Encinitas) 2015; 14(1): 34^~39].The newly made osteocalcin, however, is inactive, and it needs vitamin K2 (MK-7) to become fully activated and bind calcium [Maresz K. Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integr Med (Encinitas) 2015; 14(1): 34^"39]. ¾ [Hauschka PV. Osteocalcin: The Vitamin K-dependent Ca++-binding Protein of Bone Matrix.

Haemostasis 1986; 16(3-4): 258-272].

The calcium-uptake facilitating action makes vitamin K2 a major player in bone health and a vital need for menopause duringwhich the skeleton becomes brittle in over half the women population [Aggarwal N, Raveendran A, Khandelwal N, SenRKJhakur J S, Dhaliwal LK, 3ft, Singia V and Manoharan SRM. Prevalence and Related Risk Factors of Osteoporosis in Peri- and Postmenopausal Indian Women. J Midlife Health 2011; 2(2): 81-85].

Few illustrative examples of currently available compositions containing isoflavones derived from plant products rich in them in various combinations are as follows.

1. Per serving (5 capsules):

3¾ Soy isoflavones concentrate ΰ 50 mg

This ingredient of this product are directed to provide relief from hot flushes, cold sweats, repeated urinary tract infections, narrowing of blood vessels and vaginal dryness [Poluzzi E, Piccinni C and De Ponti F. Phytoestrogens in Postmenopause: The State of the Art from a Chemical, Pharmacological and Regulatory Perspective.

Itl Curr Med Chem 2014; 21(4): 417-438].

2. Per serving (1 caplet):

Soy isoflavones ΰ 25mg

Calcium carbonate ΰ 600mg

Cholecalciferol ϋ 200 IU

Besides the action of isoflavones as mentioned, the calcium and Cholecalciferol (vitamin D) have been known to provide calcium to the bones for its re-mineralization; this is necessary since the postmenopausal women is afflicted by postmenopausal osteoporosis. Isoflavones provide relief from hot flushes, cold sweats, repeated urinary tract infections, narrowing of blood vessels and vaginal dryness; the calcium and vitamin D (C holecalciferol) can additionally, to some extent, benefit the brittle ¾ bones.

3. Per serving (2 capsules):

S oy isoflavone concentrate ΰ 100 mg

C ranberry concentrate ΰ 400 mg

The symptoms treated by S oy isoflavone concentrate and its limitations are already ft, elaborated above. C ranberry extract of this product are directed to provide relief from repeated urinary tract infection, which is common for a menopausal woman [Bosmans J E , Beerepoot MAJ and G eerlings S E . C ost- Effectiveness of C ranberries vs Antibiotics to P revent Urinary Tract Infections in P remenopausal Women: A Randomized C linical Trial. P LoS One 2014; 9(4): e91839]. ¾ 4. Per serving (1 tablet):

S oy isoflavone ΰ 75 mg

Calcium ΰ 200 mg

P hosphorus ΰ 100 mg

Vitamin D₃ ϋ 100 III

&\ Besides the action of isoflavones and its limitations as mentioned above, the calcium and C holecalciferol (vitamin D) have been known to provide calcium to the bones for its re-mineralization; this is necessary since the postmenopausal women is afflicted by postmenopausal osteoporosis. P hosphorus additionally provides added benefit for bone mineralization in those with inadequate intakes of this mineral in diet [Heaney R P, R ecker R R and Lappe J M. P hosphate and carbonate salts of calcium support robust bone building in osteoporosis. Am J C lin Nutr 2010; 92(1 ): 101 -106]. 5. Per serving (1 softgel capsule):

S oy isoflavones ΰ 50 mg

Calcium carbonate ΰ 500 mg

Calcitriol ΰ 0.25mcg

¾ Vitamin K2-MK7 ϋ 45 meg

Magnesium oxide ΰ 50 mg

The symptoms relieved by S oy Isoflavones and its limitations are already explained above. The roles of isoflavones, calcium and vitamin K2-7 have already been elaborated for menopause. Calcitriol is an active end-metabolite of vitamin D and

3ft, similarly facilitates calcium absorption and its deposition into the bones to benefit postmenopausal osteoporosis. Magnesium helps in maintaining balanced blood levels of calcium and is also known to independently reduce hot flushes in menopausefPark H, Parker G H and S mith TJ .A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients. S upport

5¾ Cancer C are 201 1 ; 19(6): 859-863].

6. Per serving (1 capsule):

S oy isoflavones ΰ 60 mg

Calcium carbonate ΰ 500 mg

Calcitriol ΰ 0.25 meg

1&\ The symptoms treated by S oy isoflavone concentrate and its limitations are already elaborated above. T he calcitriol of this product is directed to provide additional benefit in osteoporosis for a menopausal woman [Mok J O, J ung C H and Byun D-W.

E ndoscopic comparison of alendronate alone and the enteric-coated alendronate with calcitriol combination in postmenopausal Korean females. Korean J Intern Med *fc 2013; 28(8): 694-700].

7. Per serving (1 softgel capsule):

S oy isoflavones ΰ 75 mg

Black cohosh ΰ 20 mg Calcium carbonate ΰ 150 mg

Vitamin D₃ ϋ 100 IU

The symptoms treated by S oy isoflavone concentrate and its limitations are already elaborated above. Black C ohosh provides relief primarily from symptoms such as hot ¾ flushes for a menopausal woman but cannot tackle all the consequences of menopause [Kligler B. Black C ohosh. Am Fam P hysician 2003; 68(1 ); 1 14-1 1 6].

None of the products mentioned and other S oy Isoflavone containing products in the market are complete with respect of all the ingredients required to manage menopause fully completely. ft, F urther, isoflavones cannot benefit the menopause female in all aspects unless it is accompanied by C hora (Angelica archangelica), Ashwangandha (Withaniasomnifera) and Turmeric (C urcuma longa)[C ompton J , van Amelsvoort T and Murphy D.Mood, cognition and Alzheimer's disease. Best P ract R es C linObstetGynecol 2002; 1 6(3): 357-370]. This is because menopause is a multi-symptom state and sexual organs degeneration, memory ¾ lapses and cognitive dysfunction are an inherent part of the process [G enazzani AR, S pinetti A, Gallo Rand Bernardi F. Menopause and the central nervous system: intervention options. Maturitas 1999; 31 (2): 103-1 10]. U pto 40% of menopausal women [Bachmann GA and Nevadunsky NS . Diagnosis and Treatment of Atrophic Vaginitis. American Family P hysician 2000; 61 (100): 3090-3096] have vaginal atrophy indicating degeneration and with &\ consequential decline in sexual pleasures.

Still further, there are no soy isoflavones based products that are comprehensive and provide ingredients to tackle mood, sexual intimacy disturbances, cognition and memory concerns that are inherent of the menopause state.

This invention comprises a product comprising isoflavones. T his product reduces the risk of the consequences due to stoppage of periods including the long-term changes, which are known to occur during menopause. Isoflavone content of S oybeans is2-4 mg/g, and the same of lentils and beans is about 0.002 mg/g. T hus, soy and soy products are the richest source of isoflavones.

S oybeans, soy flour and soy chips have significant concentrations of isoflavones as compared to inconsequential amounts present in tofu, soy milk and soy cheese. However, ¾ the soybeans provide inactive ^" precursors of isoflavones that need to be converted to their active counterparts.

There are three major isoflavones found in S oy: genistein, daidzein and glycitein. E ach of these isoflavones can occur in two types or states. T he first type, predominant in raw soy products, is called an ^"isoflavone glycoside._. In an isoflavone glycoside, the isoflavone is ft, attached to a sugar-like substance known as a ^"glycone. _ T he second type, predominant in fermented soy products, is called an ^"isoflavone aglycone. _ T hese consist of isoflavones without a glycone attached, and are also called ^"free isoflavones._. S ince isoflavoneaglycones are the most pure form of isoflavones, it has been regarded that they are more effective than other forms ¾ (http://healthlibrary.epnet.eom/G etc ontent.aspx?token=3b2c97de-a541 -4759-9a62- 75877fb44d23andchunkiid=21778).

S U MMARY O F T HE INV E NTIO N

This invention pertains to a single serve dosage composition for menopausal women effective for relieving hot flushes, cold sweats, strengthening bones, protection against free &\ radicals responsible for causing cancer and skin wrinkling and other ageing changes, reducing long-term menopausal consequences and maintaining body contours, preservation of memory that could be disturbed by Alzheimer^'s disease, and adaptogenic benefit to facilitate both mood uplifting as well as enjoyable intimacy.

It is one aspect of this invention that the composition comprises a sachet, a package of powder provided with one dose measure, or a tablet of soft gelatin capsule with daily serving size equivalent to one sachet content. In one embodiment, the composition of his invention is for reconstituting once a daily for consumption as a drink. The contents of the sachet are to be mixed in approximately 150 mL of water in a glass, mixed briskly till the powder is well dispersed for consumed as a drink once daily.

¾ The composition comprises, at least, following ingredients: (a) an extract of Angelica archangelica L. or alternatively, an extract of Angelica sinensis (Oliv.) Diels, (b) an extract ofWithaniasomnifera(L) Dunal, (c) an extract of C urcuma longa L, (d) an extract of Angelica archangelica L, (e) S oy isoflavones, (f) Calcium and (g) Vitamin D. Other therapeutically/P harmaceutically Active Ingredients may also be added to this composition. ft, The additional ingredients may comprise vitamins at a level of upto 100% R ecommended Daily Allowance (R DA) or, where R DA is not determined, at a level that is considered as desirable for general health maintenance.

The S oy isoflavone in this composition comprise a concentrated extract standardized to provide isoflavones genistin and genistein 24%, daidzin and daidzein 24%. ¾ The composition may also be added, further, Milk Calcium or any other source of highly bioavailable calcium; and flavors, sweeteners and other excipients. F lavors added in illustrative formulation are a cola flavor or cranberry flavor.

DETAIL E D DE S C RIPTIO N OF T H E INVE NTIO N

This invention comprises a composition for oral consumption, which comprises active &\ isoflavones: primarily genistein and daidzein. T he composition of this invention distinguishes itself over prior art soy composition on better and more reliable efficacy in terms of benefits it is capable of providing. There are an array of manifestations and implications of menopause which are not addressed so far in a single product meant for menopausal women; and the instant invention, for the first time, has addressed to all the known manifestations of significant importance as identified here 30% of women have complaints pertaining to changes in menopause; 25% opine that menopause is a negative influence [Bharadwaj J A, Kendurkar S M and Vaidya P R . Age and symptomatology of menopause in Indian women. J Postgrad Med 1983; 29(4): 218-222;S rivastava M, S rivastava R and Pandit B. P resentation of Menopausal Symptoms: A Village Based C ommunity S tudy. Asian J Medical S ciences 2015; 6(1 ): 87-90]. T he other consequences of aging in menopausal women are higher risk

¾ of cancer, putting on weight (and a change in body contours), and experiencing the usual aging-related changes such as wrinkling of skin due to free radicals. Usually the estrogens, in younger non-menopausal women protect against free radicals and this benefit is lost once the menopause effect sets in [Bottai G , Mancina R, Muratori M, Di G ennaro P and Lotti T.17<f -estradiol protects human skin fibroblasts and keratinocytes against oxidative damage. J E urAcadVenereol 2013; 27(10): 1236-1243].

S oybeans naturally contain 128 mg isoflavones per 100 gm (0.13%); of these 74 mg is genistein and 46 mg is daidzein (both together: 0.12% of total soybeans) providing a ratio of 1.6 : 1 (Isoflavones contents of food, http://www.isoflavones.info/isoflavones-content.php). Usually soy protein concentrate is the best source of isoflavones when water extraction is ¾ the method used.

The product of this invention has 40% content of active isoflavones, namely genistein and daidzein, 24 + 24 mg per 120 mg soy isoflavones, and in a ratio of 1 : 1. T he isoflavones genistein and daidzein, in the product can be derived through concentrated extract of soybeansthat are available in the market

1&\ Symptoms include: [S rivastava M, S rivastava R and Pandit B. P resentation of Menopausal Symptoms: A Village Based C ommunity S tudy. Asian J Medical S ciences 2015; 6(1 ): 87-90].

L Fatigue

I Lack of energy

I Headache

^ I Hot flushes

I C old sweats I C old hands and feet

I Numbness /tingling

I Excitability / anxiety

For the abovementioned symptoms, the isoflavones, being phytoestrogens, are beneficial.

¾ However, in addition, women going through menopause can feel stressful in it Body produces two hormones when under stress, called Cortisol and adrenaline from the adrenal glands. P rogesterone and estrogen work against the impact Cortisol has on the body. T he body can buffer stress before menopause, because there are optimal levels of progesterone. Once those levels start to lower during peri-menopause, the Cortisol buffering effect ft, weakens. High Cortisol can cause the following symptoms, which are also symptoms of peri- menopause: (https://www.healthspan.co.uk/menopause-advice/depression/how-stress- affects-symptoms-of-menopause-and-what-you-can-do-about-it)

I Insomnia

I Low energy, even if getting adequate sleep

¾ I F requent colds

I C ravings for unhealthy foods

I Digestion problems like bloating

I Weight gain, especially around the middle ^" and a change in body contours

I Low sex drive

&\ i More aches and pains

I Low mood

Addressing all these complaints is quite a challenging task, no composition is available so far that would comprehensively deal with all these complaints in a single composition. T hus, solving this yet unsolved problem, which is also a long-standing need, is very much needed. Rather, no one until this invention even contemplated that a single composition is logical and simple solution to the multitude of problems faced by menopausal women. For all such additional complaints and sufferings, there are additional requirements of ingredients to tackle especially the stress, low sex drive as well as memory concerns. For all these C hora (Angelica archangelicaand Angelica sinensis), Ashwangandha (Withania somnifera) and Turmeric (C urcuma longa) would play a useful role (see table for their individual merits); for ¾ free radicals mediated aging changes antioxidants such as lycopene will tackle the consequences - primarily skin wrinkling especially in conjunction with isoflavones [Miquel J , Ram°rez-Bosc®A, Ram°rez-Bosca J V, Alperi J D. Menopause: a review on the role of oxygen stress and favorable effects of dietary antioxidants. Arch G erontolG eriatr 2006; 42(3): 289- 306]. However, no composition has even been made for menopausal women, despite longer, standing need, to include extracts of all of the above mentioned herbs also; which is a long standing problem that was not perceived at all and hence, not solved too. T his invention has perceived and solved this problem for the first time.

Thus, the product of this invention comprises of the following attributes: e C ontains all ingredients necessary to combat most changes due to menopause.

¾ e E liminates the need of additional calcium, which is commonly consumed by the elderly women.

e P rovides all the ingredients in optimal quantities to deliver the desired benefits.

In a further embodiment of this invention, this formulation is provided, preferably, as a single serve sachet for convenient once daily intake as a drink. It is also possible to provide this 1&\ formulation in any other unit dosage form, and without / with a measure, such as a spoon that would dispense daily dose of the formulation for the purpose of reconstitution for daily consumption.

The illustrated composition is provided in a sachet and the contents of which are to be mixed in approximately 1 50 mL of water, preferably chilled water, in a glass; to be mixed briskly till the powder is well dispersed and then consumed as a drink once daily. The isoflavone-based product of this instant invention can be consumed on long-term basis during the postmenopausal period. If discontinued, benefits on account of ingredients in this product will cease.

It is an embodiment of this invention that the composition of the supplement for menopausal ¾ women comprises extracts of Angelica archangelica L. (or alternatively, extract of Angelica sinensis (Oliv) Diels, Withania somnifera L. Dunal, C urcuma longa L, Angelica archangelica L, S oy isoflavones, Calcium and Vitamin D. The composition may also additionally be supplemented with additional vitamins at a level of upto 100% R ecommended Daily Allowance (R DA) or, where R DA is not determined, at a level that is considered as desirableft, for general health maintenance. S oy isoflavones may be preferably sourced from a concentrated extract standardized to provide isoflavones G enistin and G enistein24%, Daidzin and Daidzein24%.

Table 1 provides information on the active ingredients used in the illustrative composition of¾ this invention, their action and their content in the composition.

Table 1 : The main benefit of various ingredients in the composition of this invention, (all articles full text enclosed as per the references quoted)

AVAILABLE IN

PRODUCT PER SERVING

INGREDIENT PRIME ACTION RECOMMENDED INTAKE SACHET (1 SERVING DAILY)

Manganese Strengthens 0.4-11 mg daily 2 mg

Vitamins D₂ ^(2,/D₃ bones. 80-2000 IU daily 400 IU

Vitamin K2-7^W 22.5 mcg-200 meg daily¹³' 22.5 meg

Grape seed Protects against

50-900 mg daily⁽⁴⁾ 150 mg Extract free radicals

Vitamin C responsible for 8-2000 mg daily 40 mg

Vitamin E aging changes. 1.5-1000 IU daily 7.5 IU

Extract of

Angelica

archangelica L.

(Chora) / Radix,

0.5-12g daily⁽⁵⁾ 300 mg or Extract of Adaptogens ^"

Angelica sinensis facilitate mood

(Oliv.) Diels uplift as well as

(Dong quai) enjoyable

Extract intimacy.

ofWithania

somnifera L, 300-1200 mg daily⁽⁵⁾ 500 mg Dunal,

(Ashwagandha)

Preserves

memory that

Extract of

could be

Curcuma longa 100-6000 mg daily⁽⁷⁾ 500 mg

disturbed by

L. (Turmeric)

Alzheimers

disease.

Preserves

Extract of Piper

memory that

nigrum LJor

could be

Extract of Piper 5-15 mg daily⁽⁸⁾ 5 mg

disturbed by

longum L.

Alzheimers

(Piperine)

disease.

0.2-300 mg

Thiamine (B-i) 1 mg daily⁽⁹⁾

0.24-60 mg

Riboflavin (B₂) 1.2 mg

B-i, B₂, B₃, B₅, B₆, Fulfill the nutrient daily⁽¹⁰⁾

B-12, folic acid and needs in the 2.4-35 mg Niacinamide

12 mg biotin elderly. daily (B₃)

1 -10000 mg Pantothenic acid

5 mg daily⁽¹¹⁾ (B₅)

0.4-100 mg Pyridoxine (B₆) 2 mg AVAILABLE IN

PRODUCT PER SERVING

INGREDIENT PRIME ACTION RECOMMENDED INTAKE SACHET (1 SERVING DAILY)

daily

20-1000

Folic acid (B₇) 100 meg meg daily.

0.2-100 Cyanocobalamin

1 meg

meg daily⁽¹⁰⁾ (B₁₂)

6-40000 mg

Biotin 30 meg

daily⁽¹²⁾

(1) Cooper K. Dosage of Soya Isoflavones. http://Www.livestrong.com/article/457136- dosage-of-soy-isoflavones/.

(2) Derived as an ingredient of natural/nature derived product.

¾ (3) http://omegavia.com/vitamin-k2-part-2/.

(4) Grape seed. https:/Www.drugs.com/npp/grape-seed.html.

(5) Angelica sinensis. http://Www.mayoclinic.org/drugs-supplements/dong-quai/dosing/hrb- 20059206.

(6) Recommended Ashwagandha Dosage: How Much Should You Consume? 3ft, http://Www.curejoy.com/contentashwagandha-dosage/.

(7) Curcumin. https://examine.com/supplements/curcumin/.

(8) https://nootriment.com/piperine/.

(9) Thiamine (Vitamin B1). https://medlineplus.gov/druginfo/natural/965.html.

(10) What is the maximum dosage of B vitamins? http://Www.dotfit.com/content-35903.html. 3¾ (11) http://Www.acne. org/messageboardAopic/277062-how-to-safely-mega-dose-on-b5- pa ntothenic-acid/.

(12) What is Biotin? http://Www.everydayhealth.com/drugs/biotin.

Bioavailability of calcium is crucial and it differs from source-to-source. A product prepared 1&\ from milk, commonly known as ^"Milk Calcium_, is considered highly bioavailable source of calcium. This is used in current illustration. This is essentially a minerals concentrate commonly prepared from liquid skim milk by steps comprising separation of proteins, ultarfiltration, followed by precipitation of solids which are spray dried to provide a white to creamy powder having with characteristic flavor and bulk density of ¾ IZl ίΤϋ, U, t& AlXT ii^CEfdDIE percent) having Moisture 5.0, Protein (DB) 5.0, Lactose 1.0, Fat % 0.5, pH (10% Dispersion at 201 C) 6.5 - 7.0, Total Minerals (DB) 75.0, Calcium 26.0, Phosphates 34.0, Sodium 1.0. Potassium 1.0, Chloride 1.0. However, any other course of calcium which has good bioavailability that is capable of providing the calcium stipulated in the examples provided below may be used to make the composition of the instant invention.

Foods providing 20% or more of the DV are considered to be high sources of a nutrient but foods providing lower percentages of the DV also contribute to a healthful diet. (National ¾ Institutes of Health. https://ods.od.nih.gov factsheets/Calcium-HealthP rofessional/). Hence, in the above table the minimum values are taken as 20% of the R DA for Indians as per the Indian C ouncil of Medical R esearch (IC MR ); the maximum levels for vitamins and minerals are taken as per the amounts mentioned for women in Dietary R eference Intake: Vitamins / Minerals as per the NIH (US ). ft, Menopause is a complex physiological process with a multitude of symptoms as well as long-term consequences. It commences gradually and does not lead to any sufferings in many women leading to its non-recognition as a harbinger of complications later in life. S ince the estrogens are known protective for bones, bladder, brain and heart their depletion in the menopausal phase is a definite cause for complications that are bound to occur. E strogens ¾ per se, if supplemented, can cause cancer of breast and uterus and hence the advocacy of HT is no more rampant. Instead, their natural counterparts, the relatively safer phytoestrogens, provide all the benefits without the associated cancer concern. But phytoestrogens in the form of isoflavones cannot address all the long-term consequences of menopause such as mood swings and depression, memory lapses, cognition, brittle bones &\ and diminished sexual gratification. Thus, when isoflavones are suitably complemented by suitable other natural ingredients the end-benefit is comprehensive.

Thus, in one aspect this invention is a single serve sachet of blend of ingredients to tackle all symptoms as well as long-term consequences of menopause comprehensively. No composition meant for menopause currently available serve this purpose.

In a further embodiment, this is a menopause composition that is available with flavors. The Examples in this specification have illustrated offer two flavors currently to suit most of the palates ^" cola and a popular fruity flavor ^" cranberry. A person skilled in the art shall understand that one or more of any other flavor suitable to popular palate may replace these flavors. T he illustrated composition is provided in a sachet and the contents of which are to be mixed with about 150 mLof water, preferably chilled water in a glass; mixed briskly till the powder is well dispersed and then consumed as a drink once daily.

EXAMP LE 1

P R O DUCT 1

C oncentrated extracts of soybeans containing the isoflavones genistein and daidzein ft, purchased from Bioextract Bangalore (address : S M 62, NG E F ancillary industrial estate, Mahadevapura post 560 048, India) were used as an ingredient for making the composition of this example.

The composition was made with following steps:

Ingredients were weighed to provide following composition per sachet: ¾ Milk calcium (from Milk) ϋ 2400mg

E quivalent to elemental calcium 600mg

Withania somnifera (40:1 extract) ΰ 500 mg

C urcuma longa (95% curcuminoids containing extract) ΰ 500 mg

Angelica archangelica (10:1 extract) ΰ 300 mg

&\ S oy isoflavones extract ΰ 120 mg (total)

Standardized to provide isoflavones (48mg total)

G enistin and G enistein 24%

Daidzin and Daidzein 24%

Vitamin D ... 400 IU

1. All individual ingredients were sieved. 2. Extracts of herbs were mixed with additives and the mixture was allowed to stand in storage for 48 hrs. (Maturation).

3. Vitamins and Minerals were mixed to provide a Vitamins and Minerals- P remix.

4. F lavours were added with F ructose.

5. Mixtures of step 2-4 were sieved.

6. The sieved mixes of steps 2-4 are charged in layers to Double cone Blender and the whole mix was blended for 1 hour.

7. S ample for organoleptic test was removed after 1 hr. of blending to ensure acceptable organoleptic properties. And corrections applied if necessary.

8. T he final mix was sieved and filled in sachets.

EXAMP LE 2 P R O DUCT 2

This product has same ingredients and is made with same method as above with th exception that extract of Angelica archangelicais replaced with extract of Angelica sinensis.

Claims

C laims :

1 . A single serve dosage composition for menopausal women effective for relieving hot flushes, cold sweats, strengthening bones, protection against free radicals responsible for causing cancer and skin wrinkling and other aging changes, reducing long-term menopausal consequences and maintaining body contours, preservation of memory that could be disturbed by Alzheimer^'s disease, and adaptogenic benefit to facilitate both mood uplifting as well as enjoyable intimacy.

2. The composition according to claim 1 comprising a sachet, a package of powder provided with one dose measure, or a tablet of soft gelatin capsule with daily serving size equivalent to one sachet content.

3. The composition according to claim 2 wherein the same is for reconstituting once a daily intake as a drink.

4. The composition according to claim 2 wherein the same is a sachet.

5. The composition according to claim 3 wherein the contents are for mixing in approximately 1 50 mL of water in a glass, mixed briskly till the powder is well dispersed for consumption as a drink once daily.

6. The composition according to claim 1 comprising, at least following ingredients: (a) an extract of Angelica archangelicaL. or alternatively, an extract of Angelica sinensis (Oliv.) Diels, (b) an extract of Withania somnifera (L.) Dunal, (c) an extract of C urcuma longa L, (d) an extract of Angelica archangelica L, (e) S oy isoflavones, (f) Calcium and (g) Vitamin D.

7. The composition according to claim7 further comprising additional vitamins at a level of upto 100% Recommended Daily Allowance (R DA) or, where R DA is not determined, at a level that is considered as desirable for general health maintenance.

8. The composition according to claim7 wherein the S oy isoflavones comprise a concentrated extract standardized to provide isoflavones G enistin and

¾ G enistein24%, Daidzin and Daidzein24%.

9. The composition according to claim7 further containing Milk Calcium or any other source of highly bioavailable calcium.

10. The composition according to claim7 further comprising flavors, sweeteners and other excipients.

1 1 . The composition according to claim wherein the flavor comprises a cola flavor or cranberry flavor.