FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. TITLE OF THE INVENTION: –:“POLYHERBAL FORMULATION FOR
MANAGEMENT OF PROSTATIC DISORDERS”
2. APPLICANT:
a) NAME : Shripad Medi-Search Pvt Ltd
b) NATIONALITY : Indian Company
c) ADDRESS : 32/2A, Erandwane, Gulwani Maharaj Road,
Pune 411004, Maharashtra, India.
(a)
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which
it is to be performed.
2
Polyherbal Formulation for Management of Prostatic Disorders
Field of The Invention
The present invention relates to 5 polyherbal formulation for management of prostatic
disorders including managing / treating benign prostatic hyperplasia (BPH). The
polyherbal formulation of the present invention contains in a single composition at
least 14 herbal, preferably at least 15 herbal and most preferably at least 16 herbal
compositions in low amounts / doses selected from one or more of Achyranthes
10 aspera (Apamarg), Boerhavia Diffusa (Punarnava: Hog Weed), Crataeva Nurvala
(Varuna), Tribulus Terrestris (Gokshura or gokhru), Bauhinia Variegata (Kanchnaar
Guggul), Zingiber Officinalis (Ginger), Piper Nigrum (Miri), Piper Longum
(Piper), Terminala Chebula (black- or chebulic myrobalan), Terminalia Bellerica
(baheda), Embelica Officinalis (Amalakki), Cinnamomum Tamala (Indian bay
15 leaf), Elletaria, Cardamomum (green cardamom), Cinnamomum Zeylanicum,
Hordeum Vulgare, Camphora Mukul, and additionally contains a mineral
composition preferably low amount / dose of a mineral Zinc in the form of Bhasma.
Hence polyherbal formulation is also referred as polyherbo-mineral formulation.
Single composition can be a unit composition such as pill, powder in sachet, tablet,
20 capsule etc. A single composition has combined low amounts / doses of all
polyherbal ingredients and at least one mineral ingredient Zinc, all accommodated
in unit formulation such as a tablet or a capsule or a sachet.
Additionally, some amount of inactive ingredients such as diluent, binder, glidant,
lubricant and disintegrant etc. can be added. Such composition is hereinafter
25 referred as polyherbo-mineral composition. Low amount / dose means amounts not
more than 200 mg, preferably not more than 150 mg, more preferably not more
than 100 mg and most preferably not more than 75 mg. Most preferably, herbal and
mineral medicines are employed in an amount / dose from 10 mg – 70 mg in a
formulation. The polyherbo-mineral composition of the present invention can be
30 given in addition to standard of care (SOC) to alleviate the symptoms of BPH , and
thus improve the quality of life of patients.
3
Background of The Invention
Prostate enlargement and painful lower urinary tract symptoms (LUTS) have been
linked to benign prostatic hyperplasia (BPH), a common and progressive clinical
condition of aging men. 5 This illness often strikes men over the age of 45 years and
is linked to erectile dysfunction. Prostate-specific antigen (PSA) is a clinically
useful diagnostic marker for prostate cancer, and thus understanding the link
between BPH and serum PSA levels is crucial. PSA levels may indicate the size of
the prostate and the seriousness of the condition. The advancement of BPH is
10 associated with blood PSA levels > 1.5 ng/mL and prostatic volumes > 30 mL.
When BPH worsens, it causes more severe LUTS, lowers quality of life (QOL), and
often necessitates surgery.
There are several herbal and nutraceutical products in the market to alleviate the
symptoms of enlarged prostate and the lower urinary system. Two prostatism15
related disorders, mootrakruchra and mootraaghaata were identified.
Mootrakruchra (strangury) causes considerable discomfort when urinating, while
mootraaghaata suppresses or intermittently flows urine.
Dr. Murali Manohar Chirumamilla in his article, “Prostate Gland Enlargement and
20 Ayurvedic Treatment” reports as follows:
“Natural therapies have a long history of use in our country to support optimal
prostate health. Gokshura (gokhru), whose botanical name is Tribulus terrestris,
has been traditionally used in treating urogenital conditions. Take two teaspoons of
the fruit, grind coarsely, and bring to a boil in two cups of water until about half
25 the water remains. Take a cup of this. You can also take it along with sugar and milk
if you prefer. Gokshura may also be brought to a boil in milk. Similarly, two other
botanicals deserve mention here. Both varuna (Crataeva religiosa) and punarnava
(Boerhaavia diffusa) have been shown to be effective for symptoms of BPH. In
different clinical trails, both these have shown significant anti-inflammatory effect,
30 especially pertaining to genito-urinary tract.
4
Kshaaras are the alkaline salts obtained from the ash of medicinal plants. Yavakshaara
is one such substance obtained from dried wheat plant, before blooming.
This contains altered form of potassium carbonate, which is indicated in
enlargement of the glands with special concern to prostate.
Long-term insufficient zinc intake is also 5 linked to BPH. Good dietary sources of
zinc include meat, eggs, and seafood. Yassada bhasma, obtained by calcination of
zinc is the specific medicine for this purpose. A daily dose of 125 to 250 mg with
honey will give relief from the problem.Early & mild cases respond well to Chandra
prabhavati, 2 tablets twice a day with warm milk.”
10 Thus, this article proposes use of several herbal medicines including varuna
(Crataeva religiosa) and punarnava (Boerhaavia diffusa) for optimal prostate health.
Alankar Shrivastava and Vipin B. Gupta have discussed and reported in their review
article titled, “Various treatment options for benign prostatic hyperplasia: A current
update”, BPH and Ayurveda and various herbomineral medicines mentioned in
15 various research articles / papers. Accordingly, both varuna (Crataeva religiosa) and
punarnava (Boerhaavia diffusa) have been shown to be effective for symptoms of
BPH. In different clinical trials, both these have shown significant antiinflammatory
effect, especially pertaining to genito-urinary tract. Varunadi Vati can
be prepared from the tree Crataeva nurvala also known as Varuna in Ayurveda. The
20 herbal tablets made from the bark of this tree are recommended in Ayurveda for
prostate enlargement or BPH. It improves the urinary flow rate as reducing postvoid
residual urine.
Alankar Shrivastava and Vipin B. Gupta have also reported following combinations
for treating enlarged prostrate.
25 a) Chandraprabha vati - This is a mixture of Purified Shilajit (Black bitumen),
Purified Guggulu (Balsamodendron mukul), Karpoor (Camphora), Musta (Cyperus
rotundus), Kiratatikta (Swertia chirata), Guduchi (Tinospora cordifolia),
Daruharidra (Berberis species), Pippalimool (Piper longum), Chitraka (Plumbago
zeylanica), Dhanyaka (Coriandrum sativum), Triphala, Vidanga (Embelia ribes),
5
Trikatu, Saindhava (Rock salt), Twak (Cinnamon), Ela (Elettaria cardamomum),
Vansalochan (Bambusa arundinacia).
b) Kanchnaar Guggul along with Varunadi vati and Shilajit Capsules.
c) Tablet of Bangshil which contains Shilajit (Asphaltum), Guggul
(Balsamodendron Mukul), 5 Svarnamakshika Bhasma (Ferri sulphuratum), Kasis
(Ferr: sulphas), Vanslochan (Ba.mbusa arundinaecia), Bang Bhasma (Tin Bhasma),
Sandalwood oil Chandraprabha Co.
Other medicines that are discussed by Alankar Shrivastava and Vipin B. Gupta
include Ushira (Vetiveria zizanioides), Swet Chandan (Santalum album), Areca
10 catechu, Asparagus racemosus, Sphaeranthus hirtus, Orchis mascula and many
more.
Planet Ayurveda.com under “Herbal medicines for prostrate disorders” states
following herbal remedies for BPH
(Refer https://www.planetayurveda.com/herbal-remedies-for-prostate-disorders/).
15 1. Varunadi vati (prepared from Crataeva Nurvala) – 2 tablets twice daily.
2. Tribulus Power (Standardized extract of Gokshur - Tribulus Terrestris) – 2
capsules twice daily.
3. Shilajit capsules – 2 capsules twice daily.
4. Kanchnaar Guggul (Combination of Camphora Mukul and Bauhinia
20 Variegata) – 2 tablets twice daily.
Nothing is available on efficacy of any of the above medicines. A paper is available
on “Clinical Efficacy of Chandraprabha Vati In The Management Of Urinary Tract
Infection” (Vd. Snehal Rachchawar et al, 2023) which does not mention effects of
Chandraprabha vati in BPH.
25 Reduction of International Prostate Symptom Score (IPSS) from baseline to EOT
by any of the above mentioned medications is unknown. Additionally, the
medicines which are mentioned by planet ayurveda.com might have been employed
in very high doses and hence safety also can be a concern.
6
There is a need in the art to produce a formulation which can exhibit clinical
efficacy by exhibiting reduction in International Prostate Symptom Score (IPSS)
from baseline to EOT.
There is a need for large-scale studies to evaluate the spectrum of treatments used
to treat LUTS and BPH in daily practice 5 and compare the results across treatments
The efficacy and safety of treatments like a standard of care (SOC) in terms of
alpha-adrenergic blockers, phytotherapy, and combination therapy have been
assessed in numerous clinical trials.
The Quality of Life in Benign Prostatic Hyperplasia (QUALIPROST) study was
10 conducted to evaluate the QOL of a large group of patients with moderate to severe
LUTS or BPH who were treated with therapies commonly used in clinical practice
[Alcaraz A et al, 2016].
The present invention aims to develop new polyherbo-mineral formulations
wherein several herbal medicines in the form of a composition such as dry extract
15 / Kshar can be combined with mineral zinc in the form of Bhasma for treating BPH
patients. Polyherbo-mineral compositions apart from 14 – 16 herbal medicines in
the form of dry extract optionally having Apamarg (Achyranthes aspera) in the form
of kshar instead of dry extract and at least one mineral which is preferably Zinc in
the form of Bhasma
20
Object of the invention
The first object of the present invention is to provide a polyherbal formulation for
management of prostatic disorders including managing / treating benign prostatic
25 hyperplasia (BPH). The polyherbal formulation has low amounts / doses of at least
14 dry herbal extracts, preferably 15 dry herbal extracts and more preferably 16 dry
herbal extracts or 15 dry herbal extracts and one Kshar of Apamarg. Preferably,
polyherbal formulation has low dose of one or more mineral in the form of Bhasma.
More preferably, the polyherbal formulation has low doses of at least 15 herbal
30 extracts and one mineral in the form of Bhasma. Most preferably, the polyherbal
7
formulation has low doses of 16 herbal extracts and at least one mineral Zinc in the
form of Bhasma in a single formulation. Low amount / dose means amounts /doses
not more than 200 mg, preferably not more than 150 mg, more preferably not more
than 100 mg and most preferably not more than 75 mg. Most preferably, herbal and
mineral medicines are employed in a 5 dose from 10 mg – 70 mg in a formulation
making it a polyherbo-mineral composition. The polyherbal formulation of the
present invention alleviates the symptoms of BPH and improves the quality of life
of the patients. The polyherbo-mineral formulation is useful in management of
prostatic disorders including management of / treating moderate to severe benign
10 prostatic hyperplasia (BPH) characterized by International prostate symptom score
of up to 19.
The changes in IPSS-storage, voiding and QoL scores are observed.
Second object of the present invention is to provide a polyherbo-mineral
formulation comprising compositions of Achyranthes aspera (Apamarg),
15 Boerhavia Diffusa (Punarnava: Hog Weed), Crataeva Nurvala (Varuna), Tribulus
Terrestris (Gokshura or gokhru), Bauhinia Variegata (Kanchnaar Guggul), Zingiber
Officinalis (Ginger), Piper Nigrum (Miri), Piper Longum (Piper), Terminala
Chebula (black- or chebulic myrobalan), Terminalia Bellerica (baheda), Embelica
Officinalis (Amalakki), Cinnamomum Tamala (Indian bay leaf), Elletaria,
20 Cardamomum (green cardamom), Cinnamomum Zeylanicum, Zinc, Hordeum
Vulgare, Camphora Mukul. Compositions are most preferably dry extracts for most
herbal medicines and Bhasma for zinc, however for Apamarg (Achyranthes aspera)
instead of Dry Extract Kshar can be employed.
Third object of the present invention is to provide a polyherbo-mineral composition
25 in a unit dosage form such as tablet, capsule etc.
Fourth object of the present invention is to provide a simple process of preparing
polyherbomineral formulation containing low amounts / doses of at least 14 dry
herbal extracts, preferably 15 dry herbal extracts and more preferably 16 dry herbal
extracts or 15 dry herbal extracts and one Kshar of Apamarg. Preferably, polyherbal
8
formulation has low dose of one or more mineral in the form of Bhasma preferably
zinc in the form of bhasma.
Fifth object of the present invention is to provide the polyherbo-mineral formulation
which can be given to the patient in addition to standard of care (SOC) medicines
generally used for 5 management of prostatic disorders including treating benign
prostatic hyperplasia (BPH) and is effective in reducing urine-related symptoms
and improving the Quality of Life (QoL) of BPH patients.
Summary of the Invention
10 Under a first aspect, the present invention provides a polyherbal, more specifically
polyherbo-mineral formulation for management of prostatic disorders including
benign prostatic hyperplasia (BPH) wherein the management also includes treating
Benign Prostatic Hyperplasia (BPH) comprising compositions of each of
Achyranthes aspera (Apamarg), Boerhavia Diffusa (Punarnava: Hog Weed),
15 Crataeva Nurvala (Varuna), Tribulus Terrestris (Gokshura or gokhru), Bauhinia
Variegata (Kanchnaar Guggul), Zingiber Officinalis (Ginger), Piper Nigrum (Miri),
Piper Longum (Piper), Terminala Chebula (black- or chebulic myrobalan),
Terminalia Bellerica (baheda), Embelica Officinalis (Amalakki), Cinnamomum
Tamala (Indian bay leaf), Elletaria, Cardamomum (green cardamom),
20 Cinnamomum Zeylanicum, Zinc, Hordeum Vulgare, Camphora Mukul.
According to another aspect, the present invention provides a polyherbal, more
specifically, a polyherbo-mineral formulation for management of prostatic
disorders including treating Benign Prostatic Hyperplasia (BPH) comprising low
amounts / doses of 16 herbal medicines and 1 mineral Zinc in a single unit
25 composition. Lower amounts of medicines is very important parameter because
herbal medicines are generally employed in higher amounts / doses such as 200 mg
and above, 300 mg and above and more preferably in 500 mg and above. Low
amount / dose means amounts /doses not more than 200 mg, preferably not more
than 150 mg, more preferably not more than 100 mg and most preferably not more
30 than 75 mg. Most of the amounts / doses of dry herbal extracts are selected from
9
10 mg to 70 mg so that total active content is less than 1000 mg, preferably less
than 750 mg , more preferably less than 600 mg and most preferably less than 500
mg and yet these medicines act synergistically to produce significant effect as
reflected from clinical study.
According to yet another aspect, 5 invention provides a simple process to prepare a
polyherbal, more specifically, a polyherbo-mineral formulation for management of
prostatic disorders including treating Benign Prostatic Hyperplasia (BPH)
comprising low amounts / doses of 16 herbal medicines and 1 mineral Zinc in a
single unit composition. The process employs simple equipments and machines
10 such as grinder, sifter, blender, rapid mixer granulator, sachet and capsule filling
machines, tablet compression machine and tablet coating machine which are easily
available in any manufacturing plant. The process involves first preparing
composition of each herbal medicine including composition of a mineral and then
combining such compositions in a mixer and further blending with excipients
15 selected from one or more of the diluent / filler, binder, glidant and lubricant and if
needed a disintegrant. Alternatively, compositions of herbal medicines are mixed
and then the mixture is granulated with a binder. Water, alcohol selected from
ethanol or isopropyl alcohol or water and alcohol mixture (hydroalcoholic mixture)
can be used for granulation. Binder can be a starch paste or binder can be one or
20 more of polyvinyl pyrrolidone, copovidone, hydroxy propyl methyl cellulose etc..
Preferred composition of herbal medicine is a dry extract which is prepared by first
grinding herbal medicine and then extracting it with a solvent 3 times of medicine
to prepare an extract which is distilled to prepare a distillate which is dried and
ground and sifted. For Apamarg, preferred composition is also Kshar. For zinc,
25 preferred composition is Bhasma.
In one more aspect, the invention provides a polyherbal / polyherbomineral
formulation for use in Management Of Prostatic Disorders including treating
Benign Prostrate Hyperplasia preferably in addition to standard of care treatment.
10
Invention provides a polyherbo-mineral formulation which can be given to the
patient and is effective in reducing urine-related symptoms and improving the
Quality of Life (QoL) of BPH patients.
5 Brief Description of Figures
Figure 1 illustrates flow diagram of patients where four stages viz. enrolment into
clinical trial, allocation of treatment whether SOC or SOC plus IP, follow up and
analysis are indicated.
10 Figure 2 provides preparation of dry Herbal extract wherein ground herbal
ingredients are subjected to water / solvent and the solution is distilled to obtain
distillate which is dried and subjected to grinding and sifting to remove lumps and
to obtain dry powder.
Figure 3 provides powder preparation which can be filled in sachet or capsules.
15 After dispensing, all materials are subjected to grinding, and further to sifting and
then blending with each other and with inactive ingredients. Blend is filled into
sachet or capsule.
Figure 4 provides preparation of tablets incorporating dry Herbal extract powder.
After sifting all dry herbal extract powders, they are blended with inactives /
20 excipients and compressed into tablets. Alternatively, granulation can be done in a
mixer such as rapid mixer granulator followed by drying and then blending with
inactive ingredients followed by compression. Granulation is done in a mixer such
as rapid mixer granulator using a binder selected from starch paste, polyvinyl
pyrrolidone, copovidone, hydroxy propyl methyl cellulose and solvent preferably,
25 water; or using an aqueous, alcoholic or hydroalcoholic solution of the binder to
obtain granules, Optionally, tablets can be coated. Film coating using a simple
polymer such as hydroxypropyl methyl cellulose can be done. Coating solution may
have a suitable plasticizer such as polyethylene glycol, propylene glycol, triethyl
citrate. Weight build up due to coating is preferably up to 10 % and more preferably
30 up to 5 % w/w of the compressed tablets.
11
Detailed Description of the invention
The present invention provides a polyherbal, more specifically, a polyherbo-mineral
formulation for management of prostatic disorders including treating Benign
Prostatic Hyperplasia (BPH). The polyherbo-mineral formulation contains all
ayurvedic or herbal / mineral medicines 5 accommodated in a single formulation. The
polyherbo-mineral formulation is useful in treating moderate to severe BPH
characterized by International prostate symptom score of up to 19.
Invention provides a polyherbo-mineral formulation which can be given to the BPH
patient and is effective in reducing urine-related symptoms and improving the
10 Quality of Life (QoL) of BPH patients.
The ayurvedic medicines (herbal as well as mineral) employed in the formulation
of the present invention are selected from herbal medicines and mineral medicines
which includes Apamarg (Achyranthes aspera) , Boerhavia Diffusa (Punarnava:
Hog Weed), Crataeva Nurvala (Varuna), Tribulus Terrestris (Gokshura or gokhru),
15 Bauhinia Variegata (Kanchnaar Guggul), Zingiber Officinalis (Ginger), Piper
Nigrum (Miri), Piper Longum (Piper), Terminala Chebula (black- or chebulic
myrobalan), Terminalia Bellerica (baheda), Embelica Officinalis (Amalakki),
Cinnamomum Tamala (Indian bay leaf), Elletaria, Cardamomum (green
cardamom), Cinnamomum Zeylanicum, Zinc, Hordeum Vulgare, Camphora
20 Mukul. Preferably, Apamarg (Achyranthes aspera) can be incorporated in the form
of dry extract /kshar . Kshar is most desirable. Zinc is incorporated in the form of
Bhasma and rest of the herbal medicines can be incorporated as their dry extracts. .
The polyherbo-mineral formulation of the present invention preferably contains all
ayurvedic ingredients in low amounts / doses accommodated in single unit
25 formulation such as a tablet or a capsule or a sachet.
Single formulation can be a unit formulation such as pill, powder in sachet, tablet,
capsule etc. A single formulation has low amounts / doses of all polyherbo-mineral
ingredients accommodated in unit formulation such as a tablet or a capsule or
powder / granules in a sachet. Low amount or low dose means amount / dose not
30 more than 200 mg, preferably not more than 150 mg, more preferably not more
12
than 100 mg and most preferably not more than 75 mg. Most preferably, herbal and
mineral medicines are employed in an amount of / in a dose of from 10 mg – 70 mg
in a formulation. The amounts in which herbal medicines or mineral medicines are
added whether in the form of dry herbal extracts / kshar and minerals (extract and
Bhasma) are from 10 mg to 70 mg. Never 5 before 17 ayurvedic medicines were
accommodated in such lower amounts in a single composition so that total active
content is not more than 1000 mg, preferably not more than 750 mg , more
preferably not more than
mg and most preferably not more than 500 mg.
10
Polyherbo-mineral compositions apart from 14 – 16 herbal medicines in the form
of dry extract optionally having Apamarg (Achyranthes aspera) in the form of kshar
instead of dry extract and at least one mineral which is preferably Zinc in the form
of Bhasma, contain excipients as processing aids. Processing aids can be added in
15 amounts of 0.1 – 20 % w/w. These include diluents / fillers, binders, glidants
lubricants and disintegrants. Excipients are employed in amounts of not more than
20 % w/w, preferably not more than 15 % w/w and more preferably, not more than
10 % w/w and most preferably, not more than 7.5 % w/w. Starch, cellulose, lactose
etc. can be used as a diluent /filler. Starch can be rice starch, potato starch, corn or
20 maize starch, tapioca starch etc. Binder can be starch paste, polyvinyl pyrrolidone,
copovidone, hydroxy propyl methyl cellulose. Talc, colloidal silicon dioxide and
magnesium stearate are employed as glidants and lubricants. If needed starch,
microcrystalline cellulose, sodium starch glycolate, crospovidone or
croscaramellose sodium can be added as disintegrants in amounts not more than 5
25 % w/w. More particularly, diluents are employed in amounts of 0 – 15 % w/w,
preferably from 0 – 10 % w/w, more preferably from 1 – 5 % w/w, binder from 0.25
to 5 % w/w and lubricants and glidants from 0.1 to 3 % w/w of the final formulation.
If needed, disintegrants in amount up to 5 % w/w of the composition can be added.
13
A single formulation weighs around from 300 to 600, preferably around 350 – 550
mg and most preferably from 350 – 450 mg containing low doses of 16 herbal and
one mineral medicines and suitable excipients.
Natural therapies have 5 a long history of use in our country to support optimal
prostate health. Following polyherbo-mineral medicines including mineral Zinc
are carefully chosen after referring various literatures.
Yashad Bhasma
10
Long-term insufficient zinc intake is also linked to BPH. Good dietary sources of
zinc include meat, eggs, and seafood. Yashad bhasma, obtained by calcination of
zinc is the specific medicine for this purpose.
Yashad bhasma, obtained by calcination of zinc is the specific medicine for BPH.
15 A daily dose of 125 to 250 mg with honey will give relief from the problem. It is
not possible to incorporate such large dose of Zinc Bhasma in the unit formulation
containing 15 to 16 medicines. Accordingly, Yashad Bhasma is added in an amount
of 15 % w/w of the amount prescribed.
20 Apamarg (Achyranthes Aspera)
Achyranthes Aspera is used in the treatment of boils, asthma, in facilitating delivery,
bleeding, bronchitis, debility, dropsy, cold, colic, cough, dog bite, snake bite,
scorpion bite, dysentery, earache, headache, leukoderma, renal complications,
pneumonia, and skin diseases. It can be employed as a dry extract or kshar .
25 Apamarg kshar is an alkaline Ayurvedic medicine in powder form. It helps to
manage cough and cold and condition fistula and abscess.
Piper longum (Piper), Mari (Piper nigrum) , Zingiber officinale (Sunth)-
These are described to have antiseptic and antibacterial properties; Trikatu is a
30 combination of three acrid substances: Piper nigrum known as black pepper, Piper
longum known as long pepper, and Zingiber officinale known as ginger. This
14
combination is used in more than 1500 Ayurveda formulations. Trikatu is used as a
drug of choice in various diseases of Vata and Kapha.
Inhibitory effects of crude Zingiberaceae extracts on 5αR are studied and the study
concluded that Zingiber rhizome can ameliorate oxidative stress and therefore it
5 may be beneficial in the management of benign prostatic hyperplasia.
Boerhavia Diffusa (Punarnava: Hog Weed)
It is prescribed in case of all urinary problems that are caused due to prostate
ailments.
Crataeva Nurvala (Varuna)
10 It is the tree known as Varuna in herbal / nutraceutical. The herbal tablets made
from the bark of this tree are recommended in herbal / nutraceutical for prostate
enlargement or BPH. Herbal / nutraceutical is an age old traditional medical system
still in practice in India and recognized by the WHO. Herbal non-hormonal herbal
/ nutraceutical medicine that treats BPH by reducing prostate weight. It improves
15 the urinary flow rate as reducing post-void residual urine.
Tribulus Terrestris (Gokshura or gokhru)
It has been traditionally used in treating urogenital conditions. Take two teaspoons
of the fruit, grind coarsely, and bring to a boil in two cups of water until about half
the water remains. Take a cup of this. You can also take it along with sugar and milk
20 if you prefer. Tribulus terrestris may also be brought to a boil in milk. Similarly,
two other botanicals deserve mention here. Both Crataeva religiosa (varuna) and
Boerhaavia diffusa (punarnava) have been shown to be effective for symptoms of
BPH. In different clinical trials, both these have shown significant antiinflammatory
effect, especially pertaining to genito-urinary tract.
25
Bauhinia Variegata (Kanchnaar Guggul)
This is another effective herbal remedy for enlarged prostate gland. Traditionally in
herbal / nutraceutical medicine, this herbal supplement is used for all types of
excessive growth of various tissues including prostate gland. Kanchnaar Guggul
15
(Bauhinia variegate) gives results with other supplements like Varunadi vati,
Shilajit Capsules within few days of using them.
Terminala Chebula (black- or chebulic myrobalan) and Terminalia Bellerica- A
combination of herbal / nutraceutical 5 formulation containing T chebula and
bellerica have shown inhibition of enlarged prostate gland in animal models.
Embelica Officinalis (Amalakki) – herbal / nutraceutical books also indicate
amalakki for prostatis and benign prostate hyperplasia.
10 Cinnamomum Tamala and Cinnamomum Zeylanicum-
C zeylanicum is a potent herb, Dalchini or cinnamon is used for repairing damaged
tissues and treating a host of ailments including heart problem, diabetes, neural
disorders, skin infections, cough and cold.
Cinnamomum tamala is a multipurpose evergreen plant useful for the treatment of
15 various diseases or disorders such as Cancer, cardiac diseases, diabetes, Anxiety,
depression, ulcer, GI diseases and possess many pharmacological activity includes
anti-oxidant, anti-hypercholesterolemia, anti-diarrhoeal, anti-inflammatory, antifungal,
antibacterial etc. ( Shifali Thakur et al, 2021). The bay leaf is also used for
preventing and managing diabetes, dandruff, joint pain, boils, fungal infections etc.
20 A combination of C tamala, C zeylanicum along with Kanchanara Guggulu orally
and Dhanyaka Gokshura Ghrita Matra is effective conservative management for
symptomatic relief in BPH of senile age.
Elletaria Cardamomum- From the last updates of herbal / nutraceutical
medicines, E cardamomum was prescribed for the benefits in patients with benign
25 prostate hyperplasia.
Hordeum vulgare – In a study with combination of an herbal / nutraceutical
product having H vulgare, by virtue of its properties helped in reduction of prostate
size along with post void residual collection and symptomatic relief by reduction in
Hesitancy, Urgency, frequency of micturition, nocturia and Intermittency.
16
Commiphora mukul – A study results demonstrate that CM extract not only
inhibits PCa cell growth regardless of their androgen sensitivity or p53 status, but
also sensitizes hormonerefractory PCa cells to docetaxel. CME is now being tested
in animal models to determine its preventive and therapeutic efficacy in vivo.
5
All above ayurvedic medicines are generally prescribed for various ailments in
amounts / doses which are more than 100 mg, preferably up to or more than 200 or
250 mg and more preferably up to or more than 500 mg.
In view of the above, there is no clinical study available till date evaluating the
10 efficacy of aforesaid herbal ingredients and Yashad Bhasma (Zinc in the form of
Bhasma) together in low amounts in a single formulation such as a tablet or a
capsule or a powder / granule formulation against the allopathic drugs for BPH.
Therefore, the present study involves preparing a single formulation having reduced
15 or lowered amounts / doses of 17 Ayurvedic medicines and testing their safety and
efficacy in BPH where they can synergistically act to produce effects in spite of
reduced dose or lowered amounts. Reduced amounts of various herbal and mineral
medicines are used so that such lower amounts are accommodated in a single
formulation and wherein such reduced amount / dose can be supported by a clinical
20 study to have a comparative assessment of polyherbo-mineral formulations.
Preferably formulations are tablet or capsule or a powder / granule formulations
which are tested for safety, efficacy and non-inferiority when compared to an
allopathic formulation in benign prostate hyperplasia patients.
25 Present invention provides a single composition containing from 14 – 16 herbal
medicines and preferably one mineral medicine. Most herbal medicines are in the
form of dry extract except Apamarg which can be added in the form of Kshar or as
a dry extract.
30 Table 1 below provides a polyherbo-mineral composition having 17 Ayurvedic
medicines comprising 16 herbal and one mineral medicines in stated lower amounts
17
/ proportions where no single ayurvedic medicine whether herbal or mineral exceed
30% w/w of the composition and at least 15 out of 17 medicines do not exceed 15
% w/w of the composition and wherein total active content / amount of the
formulation is not more than 600 mg, preferably not more than 550 mg, more
preferably not 5 more than 500 mg and most preferably not more than 450 mg.
Table 1: Polyherbo-mineral Compositions
Sr. No. Ingredient % w/w of composition
1 Apamarg Dry Extract / Kshar 1 – 10 %;
2 Kachnar bark dry extract 0.75 – 7.5 %;
3 Yashad Bhasma 1 – 10 %;
4 Guggul Dry Extract 1 – 10 %;
5 Tejpatta Dry Extract 0.75 – 7.5 %;
6 Cinnamon Dry Extract- 10 mgs 0.5 – 5.0 %
7 Varuna Dry Extract - 47 mgs 5 – 15 %
8 Cardamon Dry Extract- 27 mgs 1 – 10 %;
9 Amla Dry Extract -20 mgs 1 – 10 %;
10 Barley Dry Extract- 65 mgs 5 – 25%
11 Pippali Dry Extract - 10 mgs 0.5 – 5.0 %
12 Kali Mirch Dry Extract- 20 mgs 1 – 10 %;
13 Baheda Dry Extract - 20 mgs 1 – 10 %;
14 Harda Dry Extract - 20 mgs 1 – 10 %;
15 Gokhru Dry Extract- 15 mgs 0.75 – 7.5 %;
16 Saunth Dry Extract - 20 mgs 1 – 10 %;
17 Punarnava Dry Extract- 20 mgs 1 – 10 %;
Excipients Up to 20 %, preferably
up to 10 %.
Various compositions are prepared as provided under examples 2.
10
18
Processes for the preparation of Dry Extracts and compositions containing dry
extracts of Examples 1 and 2 are as follows.
Preparation of Dry Extracts
1. The active ingredients are 5 dispensed separately and subjected to grinding in
a grinder to get desired coarse or fine powder.
2. The powder mixture of step 1 is subjected to extraction using water or
solvent (preferably 3 times of water or solvent is used) and the extracted solution is
subjected to distillation to obtain distillate. Solvent used is ethanol or isopropyl
10 alcohol.
3. The distillate is dried to obtain dry extract,
4. The dry extract is further subjected to grinding using a grinder and ground
extract is sifted to remove any lumps etc. to get dry extract powder or dry extract.
15 Process for the preparation of Kshar of Achyranthes aspera (Apamarg)
1.Drying- The Apamarg dried is taken / procured and chopped into small pieces and
then dried under sunlight for up to 5 days (40 hours).
2. Burning of dried Apamarga - Dried Apamarg is taken in a large iron pan and
20 burnt into ash form till white colour ash is obtained. Then, it is left for self-cooling
(swangasheeta).
3. Then, water is added in a ratio (4,6 or 8) with 1 part ash and macerate well and
the mixture is left overnight undisturbed for a period of time (3, 12 and 72 hours).
The next morning, supernatant is collected by filtration and the dark colour
25 sediment is discarded. Then the supernatant is filtered two or three times till clear
liquid is obtained known as Ksharodaka (alkaline liquid).
4. In the next step, Ksharodaka (alkaline liquid) is heated with moderate fire with
alternating stirring for 3 hours till it turns into white colour powder.
30 Process for the preparation of unit formulation for e.g., tablet or a capsule or
powder from dry extract is as follows.
19
Preparation of unit formulation
1. Dry extracts of all ayurvedic medicines or Dry extracts of all ayurvedic
medicines except Apamarg and Apamarg kshar instead 5 of Apamarg dry extract are
dispensed and sifted through 40 mesh sieve and then mixed.
2. The mixture of step 1 is blended with one or more excipients selected from
diluent, binder, glidant, lubricant and if needed disintegrant and compressed into
tablets or filled into the capsules, or sachets; or
10 3. The mixture of step 1 or 2 is optionally granulated in a mixer such as rapid
mixer granulator using a binder selected from water , solvent or binder solution
starch paste, polyvinyl pyrrolidone, copovidone, hydroxy propyl methyl cellulose
and solvent preferably, water; or using an aqueous, alcoholic or hydroalcoholic
solution of the binder to obtain granules,
15 4. The granules of step 2 are sifted through suitable mesh and then blended
with excipients selected from glidant, lubricant and if needed disintegrant and
compressed into tablets or filled into the capsules or sachets,
5. The tablets are optionally coated. Film coating using a simple polymer such
as hydroxypropyl methyl cellulose can be done. Coating solution may have a
20 suitable plasticizer such as polyethylene glycol, propylene glycol, triethyl citrate.
Weight build up due to coating is preferably up to 10 % and more preferably up to
5 % w/w of the compressed tablets.
Thus, process chosen is a simple one requiring simple equipments such as grinder,
sifter, blender, rapid mixer granulator, sachet and capsule filling machines, tablet
25 compression machine and tablet coating machine which are easily available in any
manufacturing plant.
Further step involves subjecting formulation of Example 2 to clinical study to check
safety, efficacy and non-inferiority of said formulation. A tablet formulation
30 prepared as provided under example 2 is taken for the study.
20
A prospective, multi-center, randomized, open-label, two-arm study was designed
to evaluate the safety and efficacy of polyherbo-mineral tablet formulation
according to example 2 plus SOC when compared with only SOC in patients with
BPH. The study was conducted at four different centers in central India. A total of
140 eligible patients were assigned randomly to 5 the two treatment arms in a ratio
1:1 and followed for 12 weeks. The details of the study are as provided under
example 3.
Following primary and secondary end points are selected.
10 Primary Endpoint
Efficacy:
• Change in Total International Prostate Symptom Score (IPSS) from baseline to
EOT
15 Secondary Endpoint
Efficacy:
• Change in IPSS storage (Irritative) sub score from baseline to EOT
• Change in IPSS voiding (Obstructive) sub score from baseline to EOT
• Change in IPSS quality of life (QOL) Index from baseline to EOT
20 • Change in Qmax from baseline to EOT
• Change in PVR volume from baseline to EOT
• Change in IIEF-EF (question 1-5 and 15) score from baseline to EOT
• Proportion of participants with AE and SAE from the data of screening to EOT
• Proportion of patients having common side effects of alpha blockers from
25 baseline to EOT.
After 12-week treatment, changes in IPSS scores (Storage + Voiding) between two
groups was also performed after adjusting with baseline IPSS scores using analysis
of covariance (ANOVA).
30 The analysis of Proportion of patients achieving therapeutic response (IPSS scores)
was performed considering Mann-Whitney U test. The Proc frequency procedure
21
of SPSS version 26.0 (IBM Corp ARMONK USA) was used. The ANOVA model
include the treatment group and baseline IPSS scores as covariate. The LSM of
products and their 95% CI were estimated from ANOVA model.
The estimate of difference in least square mean of IP+SoC to SoC arm is -0.6722
and its 95% confidence interval was 5 (-1.1762, -0.1682) with P-value p<0.0001
which is statistically significant.
The upper bound of 95% confidence interval is less than 0 which indicate
superiority of test product over the reference product.
Based on the analysis, the least square mean (Standard error) of test product is
10 observed -50.7992 (10.6531), while in reference product it is -12.0060(11.0551).
The estimate of difference in least square mean of test to reference product is -
32.6897 and its 95% confidence interval observed (-51.9762, -13.4032) with Pvalue
0.0011 which is statistically significant the observed upper bound is well
15 below zero. The difference in mean change in FPG from baseline (screening) to end
of treatment visit was statistically significant.
The difference in least square mean of test to reference product is -38.7932 and its
95% confidence interval was (-67.7299, -9.8565) with P-value 0.0091 which is
statistically significant. The difference in mean change in 2-hr PPG from baseline
20 (screening) to end of treatment visit was statistically significant.
The upper bound of 95% confidence intervals were less than predefined non
inferiority margin which indicate non-inferiority of test product over the reference
product.
25 Following observations are noted during the clinical study:
• The mean age of patients differed non-significantly between two groups.
• Regarding anthropometry, BMI showed significant increase with time in both the
study groups (p<0.0001). This was contributed by the significant increase in weight
30 of patients with time in both the groups.
22
• Among vital parameters, pulse rate showed significant reduction from screening
to day 90 in both the treatment groups (p<0.0001).
• At day 90, systolic and diastolic blood pressures were significantly higher in
IP+SOC group as compared to SOC group, although clinically non-significant.
• In haematology, basophil and 5 MCHC showed significant change from screening
to day 90 in both the treatment groups.
• The between and within group differences of all the biochemical parameters were
statistically nonsignificant.
• The log-PSA level differences between and within groups were statistically non10
significant. Also, the between group comparison of change in log-PSA levels was
non-significant.
• Urine frequency reduced significantly from screening to day 90 in both the groups
(p<0.0001). At day 90, median urine frequency was smaller in IP+SOC group as
compared to SOC group. The change in urine frequency from screening to day 90
15 was significantly higher in IP+SOC group as compared to SOC group (p=0.018).
• Urine urgency score reduced from screening to day 90 in both the groups. The
change in the score from screening to day 90 differed significantly between two
groups (p=0.048). The change was higher in IP+SOC group as compared to SOC
group.
20 • Sonographic measurements differed non-significantly between groups at
screening and day 90; however, the within group change was significant in both
IP+SOC and SOC groups (p<0.0001).
• The IPSS-storage scores differed significantly between groups at day 90
(p=0.013). In IP+SOC group, the median score was lower than that of SOC group.
25 The change in score from screening to day 90 was significant in both the treatment
groups (p<0.0001). Further, the change in score from screening to day 90 differed
significantly between groups (p=0.015).
23
• The IPSS-voiding scores differed significantly between groups at day 90
(p=0.007). In IP+SOC group, the median score was lower than that of SOC group.
The change in score from screening to day 90 was significant in both the treatment
groups (p<0.0001). Further, the change in score from screening to day 90 differed
5 significantly between groups (p=0.002).
• The IPSS (storage + voiding) scores differed significantly between groups at day
90 (p=0.004). In IP+SOC group, the median score was lower than that of SOC
group. The change in score from screening to day 90 was significant in both the
treatment groups (p<0.0001). Further, the change in score from screening to day 90
10 differed significantly between groups (p<0.0001).
• The IPSS-QOL scores differed significantly between groups at day 90 (p=0.001).
In IP+SOC group, the median score was lower than that of SOC group. The change
in score from screening to day 90 was significant in both the treatment groups
(p<0.0001). Further, the change in score from screening to day 90 differed
15 significantly between groups (p=0.022).
• The IIEF scores on erectile function, intercourse satisfaction, orgasmic function,
overall satisfaction, and sexual desire showed statistically significant improvement
in IP+SOC arm from day-1 to Day 90 (P<0.05). However, in SOC arm, this change
was non=significant (P>0.05) for all the
20 parameters.
• The Qmax scores of patients were significantly higher in IP+SOC group as
compared to SOC group (p=0.035) at day 90. The increase in scores from day1 to
day 90 was significant in IP+SOC group (0.002), while non-significant in SOC
group.
25 • The minimum voided volume showed non-significant changes between and
within groups. Regarding adverse events, the proportion of patients showing AEs
at day 90 in IP+SOC group (1.4%) was smaller than that of SOC group (7.3%),
although the difference was statistically non-significant (p=0.198).
Study Endpoints
24
Conclusions
This study demonstrated the efficacy and safety of IP as a supplement to SOC. The
combination significantly increased the IPSS storage & voiding scores, and IIEF
domain scores from day 1 to day 90. Furthermore, 5 IPSS-QoL significantly
improved with IP supplementation from day 1 to day 90. This study has provided
evidence that the combination of herbal and nutraceutical products with a standard
of care provides a safe and effective option for those suffering from LUTS-related
issues in BPH patients. More clinical trials are needed to underscore the importance
10 of natural products in the management of BPH, at least as an add-on treatment, if
not as a primary role.
Examples
Following examples illustrate the invention without limiting scope of the invention
15 in any way.
A single formulation containing low doses of at least 14, preferably 15 and more
preferably 16 dry herbal extracts and a mineral zinc in the form of a Bhasma is
prepared and tested to evaluate the safety and efficacy in patients with benign
20 prostatic hyperplasia. Lower amounts of medicines is very important parameter
because herbal medicines are generally employed in higher amounts / doses such
as 200 mg and above, 300 mg and above and more preferably in 500 mg and above.
Low amount / dose means amounts /doses not more than 200 mg, preferably not
more than 150 mg, more preferably not more than 100 mg and most preferably not
25 more than 75 mg. Most of the amounts / doses of dry herbal extracts are selected
from 10 mg to 70 mg so that total active content is less than 1000 mg, preferably
less than 750 mg , more preferably less than 600 mg and most preferably less than
500 mg and yet these medicines act synergistically to produce significant effect as
reflected from clinical study.
30
25
Example 1:
Table 1:
Weight of each capsule / tablet is around from 300 – 600 mg, preferably from 350
5 – 500, more preferably from 350 – 450 mg.
Ingredient % w/w of
composition
1. Apamarg (Achyranthes aspera) Dry Extract / Kshar 1 – 10 %;
2. Kachnar bark (Bauhinia Variegata) dry extract 0.75 – 7.5 %;
3. Yashad Bhasma 1 – 10 %;
4. Guggul (Camphora Mukul) Dry Extract 1 – 10 %;
5. Tejpatta (Cinnamomum Tamala) Dry Extract 0.75 – 7.5 %;
6. Dalchini / Cinnamon (Cinnamomum Zeylanicum) Dry
Extract
0.5 – 5.0 %
7. Varuna (Crataeva Nurvala) Dry Extract 5 – 15 %
8. Cardamon (Elletaria, Cardamomum) Dry Extract 1 – 10 %;
9. Amla (Embelica Officinalis) Dry extract 1 – 10 %;
10. Barley (Hordeum Vulgare)Dry Extract 5 – 25%
11. Pippali (Piper Longum) Dry Extract 0.5 – 5.0 %
12. Kali Mirch (Piper Nigrum) Dry Extract 1 – 10 %;
13. Baheda (Terminalia Bellerica) Dry Extract 1 – 10 %;
14. Harda (Terminala Chebula) Dry Extract 1 – 10 %;
15. Gokhru (Tribulus Terrestris) Dry Extract 0.75 – 7.5 %;
16. Saunth (Zingiber Officinalis) Dry Extract 1 – 10 %;
17. Punarnava (Boerhavia Diffusa) Dry Extract 1 – 10 %;
18. Excipients selected from one or more of diluent, binder,
glidant, lubricant and disintegrant
Up to 20 %,
preferably up
to 10 %.
26
Example 2
Table 2:
Ingredient Content in mg per tablet or capsule
1. Apamarg Dry Extract /
Kshar
15 30 40 28
2. Kachnar bark dry extract 25 15 5 15
3. Yashad Bhasma 15 20 25 20
4. Guggul Dry Extract 45 30 15 28
5. Tejpatta Dry Extract 5 15 25 15
6. Cinnamon Dry Extract 15 10 5 10
7. Varuna Dry Extract 35 40 65 47
8. Cardamon Dry Extract 45 30 15 27
9. Amla Dry Extract 10 20 30 20
10. Barley Dry Extract 60 70 45 65
11. Pippali Dry Extract 5 10 15 10
12. Kali Mirch Dry Extract 30 20 10 20
13. Baheda Dry Extract 10 20 30 20
14. Harda Dry Extract 30 20 10 20
15. Gokhru Dry Extract 5 15 20 15
16. Saunth Dry Extract 30 20 10 20
17. Punarnava Dry Extract 10 20 30 20
Weight 390 405 395 400
Excipients 4 - 20 4 - 20 4 - 20 4 - 20
Total unit weight
394 - 410 409 - 425
399 -
415
404 -
420
5
Preparation of Dry Extracts
27
1. The active ingredients are dispensed separately and subjected to grinding in
a grinder to get desired coarse or fine powder.
2. The powder mixture of step 1 is subjected to extraction using water or
solvent (preferably 3 times of water or solvent is used) and the extracted solution is
5 subjected to distillation to obtain distillate.
3. The distillate is dried to obtain dry extract,
4. The dry extract is further subjected to grinding using a grinder and ground
extract is sifted to remove any lumps etc. to get dry extract powder or dry extract.
10 Yashad Bhasma was procured from market. Alternatively, Yashada bhasma is
prepared by a three step process i.e. Shodhan (purification), Jarana (polling) and
Marana (incineration).
Process for the preparation of unit formulation for e.g., tablet or powder for
15 sachet or capsule filling.
1. All the active ingredients and excipients are dispensed, ingredients are
subjected to grinding if required and sifted through 40 mesh sieve and then mixed,
2. The mixture of step 1 is blended with one or more excipients selected from
diluent, binder, glidant, lubricant and if needed disintegrant and compressed into
20 tablets or filled into the sachets or capsules, or
2. The mixture of step 1 or 2 is optionally granulated in a mixer such as rapid
mixer granulator using water / solvent such as alcohol selected from ethanol or
isopropyl alcohol; or hydroalcoholic mixture or binder solution in water, alcohol or
hydroalcoholic solvent in a mixer such as rapid mixer granulator wherein a binder
25 is selected from starch, polyvinyl pyrrolidone, copovidone, hydroxy propyl methyl
cellulose to obtain granules,
3. The granules of step 2 are sifted through suitable mesh and then blended
with one or more excipients selected from diluent, glidant, lubricant and if needed
disintegrant and compressed into tablets or filled into the capsules,
30 4. The tablets are optionally coated. Film coating using a simple polymer such
as hydroxypropyl methyl cellulose can be done. Coating solution may have a
28
suitable plasticizer such as polyethylene glycol, propylene glycol, triethyl citrate.
Weight build up due to coating is preferably up to 10 % and more preferably up to
5 % w/w of the compressed tablets.
5 Example 3
Tests performed on tablets containing 16 (dry) Herbal extracts and one mineral in
the form of “Bhasma” prepared as per example 2 which is referred as
Investigational product or IP.
i) Average weight of tablet = 391.71 mg (within + 5 % w/w);
10 ii) pH of tablet = between 5.5 to 6.5;
iii) water soluble extractives – from 40 – 80 % w/w
iv) alcohol soluble extractives – from 5 – 25 % w/w;
v) pathogens S. aureus, Salmonella, E coli – absent
15 Methodology
Trial design
A prospective, multi-center, randomized, open-label, two-arm study was designed
to evaluate the safety and efficacy of herbal / nutraceutical tablet formulation plus
SOC when compared with only SOC in patients with BPH. The study was
20 conducted at four different centers in central India between 2022 and 2023. A total
of 140 eligible patients were assigned randomly to the two treatment arms in a ratio
1:1 and followed for 12 weeks.
Table 3: SOC treatment medications and dose
Sr. No. SOC details Dose
1 Silodosin 8 mg/OD
2 Dutasteride 0.5 mg/OD
3 Alfuzosin 10 mg/OD
4 Tamsulosin (flowmax) 0.4 mg/OD
5 Bethanechol 50mg/OD
29
6 Mirabegron 50mg/OD
7 Tadalafil 5mg/OD
8 L-Arginine 6 gm SOS/OD
9 Proanthocyanidin 6.5 gm SOS/OD
The active ingredients of the investigational product (IP) (provided under table 4)
consisted of herbal / nutraceutical ingredients in low doses and in certain
combination invented by present inventors. The details of the investigational
5 product ingredients are given in tables 1 - 2.
Participants
A total of 176 patients were screened at all four centers to attain the target sample
of 140 patients. The patients were randomized to the two arms using block
10 randomization of size two. Male patients in the age range of 18 to 65 years
diagnosed with BPH, having international prostate symptom score (IPSS) more
than 8, with Qmax between 5 to 15 ml/sec and voided volume > 125 ml, postvoiding
residue < 300 ml on ultrasound, and willing to participate in the study were
included for assessment. Characteristics of patients at baseline in two arms is
15 provided in table 5.
Excluded patients were those with PSA > 4 ng/ml at screening, having a history of
neurogenic bladder, urethral strictures, prostatitis, urologic cancer, and prostatic
surgery, significant bladder outflow, heart disease, uncontrolled arrhythmias,
hypertension, and those on hemodialysis.
20 Informed consent was obtained from the patients before enrolling in the study.
During the study, patients were free to withdraw their consent from the study. The
patient flow is given in Figure 1.
30
31
Drug administration
Investigational product also referred as IP is a polyherbo-mineral composition /
formulation containing combination of 16 herbal ingredients and one mineral
ingredient and suitable excipients. Excipients are added from 0.1 to 20 % w/w
depending upon whether the investigational 5 product is a tablet or a capsule or a
powder.
The active ingredients of the investigational product (IP) (provided under table 4)
consisted of herbal / nutraceutical ingredients in low doses and in certain
combination invented by present inventors. The details of the investigational
10 product ingredients are given in tables 1 - 2.
For the clinical trials, IP in the form of tablets were prepared and administered to
the test group twice daily, in the morning and evening around the same time, for a
period of 12 weeks / 90 days, in addition to SOC. The SOC consisted of allopathic
treatment. Table 3 provides SOC treatment given in both the arms. Patients were
15 not permitted to take any other medicines or Over the Counter (OTC) products
(including vitamins and products from natural origin), except those prescribed by
the Principal Investigator (PI), as essential for the well-being of the patient in the
test group.
Patients were expected to maintain compliance and accountability for all study drug
20 medication during the conduct of the study.
IP description
The herbal/nutraceutical investigational product is in the form of a tablet comprised
of ingredients as mentioned in Table 1 and having characteristics as described under
25 example 3. The allopathic treatment was the SOC (as provided in table 3) given to
patients in both treatment arms.
Efficacy & Safety evaluations
The study aimed at determining the efficacy and safety of the herbal/nutraceutical
30 (IP) in the treatment of BPH.
32
The primary efficacy variables include comparison of the change in total
international prostate symptom score (IPSS) (storage & voiding) from baseline to
end of treatment (EOT) between SOC+IP and SOC arms.
The secondary endpoints were to compare the change in: a) IPSS storage, b) IPSS
voiding, c) IPSS quality of life scores 5 d) Qmax, e) PVR f) IIEF-EF, g) urine
frequency and urgency score, from baseline to end of treatment.
The safety was evaluated in terms of adverse events (AE) and severe adverse events
(SAE), as well as common side effects of alpha-blockers, drug interaction, change
in prostate-specific antigen (PSA), biochemical, hematological, and vital
10 parameters during the study.
Ethics & regulatory authorization
The entire study was conducted following the principles of Good Clinical Practice
(GCP), the declaration of Helsinki, and Indian Council of Medical Research
15 (ICMR) guidelines for biomedical research on humans.
Statistical methods
The data on continuous parameters were summarized using mean, standard
deviation, and range, while categorical parameters were expressed in terms of
20 frequency and percentage.
The normality assumption of continuous parameters was tested using Shapiro-
Wilk’s test. Accordingly, the between-group comparisons were tested for
significance using a t-test for independent samples. The prostate-specific antigen
25 data was log-transformed and compared within the group using paired t-test, while
between groups using t-test for independent samples. Urine frequency and urgency
score across times in each group were compared using Friedman ANOVA, while
between groups at each time was compared using the Mann-Whitney U test. The
post-void residue (PVR) within and between groups were compared by Wilcoxon
30 signed-rank test and Mann-Whitney U test respectively. Further, the IPSS storage,
voiding, storage + voiding, and quality of life scores were compared within and
33
between groups using Friedman ANOVA and Mann-Whitney U test respectively.
The change in these scores from baseline to day 90 was compared between groups
using the Mann-Whitney U test.
All the analyses were performed using SPSS version 26.0 (IBM Corp. ARMONK
USA) 5 and the statistical significance was evaluated at a 5% level.
Results
The characteristics of patients enrolled in the two groups are described in Table 5.
The mean age of patients in the SOC+IP group was 53.1 ± 7.19 years while that in
10 the SOC group was 54.55 ± 6.62 years, and the difference between the means was
statistically non-significant. Further, the anthropometric parameters showed a
statistically non-significant difference between the two groups. The proportion of
patients with medical history was higher in the SOC+IP group (29.6%) than in the
SOC group (15.9%); however, the difference was statistically non-significant.
15 Overall, the patient characteristics were similar between the two groups at baseline.
The comparison of the primary endpoint, i.e. IPSS score within and between groups
is given in Table 6. The within-group comparison for IPSS (storage & voiding)
showed statistically significant change in both the treatment groups (p < 0.0001).
The median change in score from day 1 to day 90 for the SOC+IP group was
20 significantly higher than that of the SOC group with a p < 0.0001. Further, IPSS
(storage) showed a significant lowering from day 1 to day 90 in both groups with p
< 0.0001. The median change in the IPSS storage between the two time points in
the SOC+IP group was significantly higher than in the SOC group, with a p-value
of 0.015. The IPSS (voiding) showed a significant lowering from day 1 to day 90
25 in both groups with p < 0.0001. The median change in the IPSS voiding between
the two-time points in the SOC+IP group was significantly higher than the SOC
group with a p-value of 0.002. Moreover, IPSS quality of life improved
significantly from day 1 to day 90 in both the groups with a p < 0.0001. The median
change in IPSS QoL in the SOC+IP group was higher than that of the SOC group
30 with a p-value of 0.022.
34
The comparison of various secondary endpoints was also performed with the results
shown in Table 7. The parameter Qmax showed a significant increase from day 1
to day 90 in the SOC+IP group with a p-value of 0.002; however, the change was
non-significant in the SOC group. At day 90, the median Qmax in the SOC+IP
group was significantly higher than 5 the SOC group with a p-value of 0.035 (Table
7). The post-void measurement showed a significant lowering of the median from
day 1 to day 90 in both the study groups with a p < 0.0001 (Table 7).
Similarly, IIFS scores were compared within and between groups. In the SOC+IP
group, all the IIFS parameters showed significant improvement (p < 0.05), unlike
10 the SOC group. The urine urgency score showed statistically non-significant
differences within and between groups.
The biochemical, hematological, vital, and Adverse Events term-wise events are
provided in Tables 8, 9, 10 and 11.
The safety endpoints like biochemical parameters showed statistically non15
significant differences within and between groups. Regarding haematology,
basophils, and MCHC showed significant change within both the groups, while
monocytes showed statistically
significant change in the SOC+IP group, and neutrophils showed significant change
in the SOC group. The vital parameters like pulse rate and systolic blood pressure
20 showed a significant reduction in the mean levels of parameters from day 1 to day
90. There were adverse events in the SOC+IP group, while 16 were in the SOC arm
during the study.
25
35
36
37
38
39
40
41
42
43
44
Discussion on Safety and Efficacy of the treatments
Polyherbo-mineral formulation of the present invention exhibited synergistic action
of its multiple low dosed herbal and mineral constituents. These acts at multiple
levels, which need further study 5 to find out the exact mechanism. In the present
study, some promising results were observed with the herbal formulations in
addition to SOC (standard of care treatment), in the treatment of benign prostate
hyperplasia (BPH).
According to a study done by Ma X et al. (2020), herbal formulations that include
10 fatty acids and antioxidants can aid in lowering prostate gland inflammation,
enhancing urine flow, and preventing the growth of cancer cells. Additionally, it has
been discovered that herbal preparations alleviate the pain and symptoms of benign
prostate cancer, such as an increase in urine frequency and difficulty peeing.
Inclusion criteria for age in this study was Male Patients of age between 18 years
15 to 65 years (both inclusive) who were diagnosed for benign Prostatic Hyperplasia.
The age of patients diagnosed with BPH and enrolled in the study ranged from 39–
64. The symptoms are uncommon in younger men , while they are more prominent
in older men. Bijak et al. (2017) also showed that the incidence and severity of
symptoms of BPH both rise with age [Bijak, 2017].
20
The safety analysis included recording and analysing following,
• Recording Incidence of adverse events (AEs), classified according to their
seriousness, severity as per CTCAE v5.0 and AEs considered to be drug-related
• Recording vital signs (pulse rate, systolic and diastolic blood pressure (seated),
25 body temperature and respiratory rate),12-Lead ECG, Physical examination and
clinical laboratory investigations (hematology, biochemistry and urinalysis).
• Any Clinically significant abnormal change from baseline in the concurrent
medical condition(s), Physical examination and clinical laboratory data shall be
recorded as an • Incidence of SAEs and death.
30
45
The primary endpoint related to IPSS (storage + voiding) showed a significantly
low median score in the SOC+IP group as compared to the SOC group on day 90.
The change in scores from screening to day 90 was noticeable in both groups.
Further, the median change in IPSS (storage + voiding) scores from day 1 to day 90
5 was significantly higher in the SOC+IP group than in the SOC group.
This finding indicates that the IPSS V/S ratio is a more useful diagnostic tool and
can be utilized to distinguish between patients with bladder-related and bladder
outlet-related urinary tract infections. Apart from the significance of SOC+IP with
IPSS (storage + voiding), storage and voiding alone, also demonstrated substantive
10 modifications in the management of BPH when compared to SOC.
In the present study, the primary indicator IPSS-QoL indicated a significant change
in the scores from screening to day 90 in both groups. The SOC+IP group had a
significantly larger median change than the SOC group. In another study by Patel
et al. (2016), the authors also reported a significant reduction in the QoL scores
15 from baseline to six weeks. Some of the ingredients like Crataeva, Boerhavia,
Commiphora mukul were common to the present IP product. In the present study, a
significant increase in the Qmax score from day 1 to day 90 in the SOC+IP group,
unlike the SOC group is observed. In a study by Sahu et al. (2003), the authors
reported a significant increase in the Qmax scores before and after treatment with
20 their polyherbal formulation. In a study by Sokeland (2000), the author also
observed an increase in the Qmax score for the treatment group constituting sabal
and urtica extract. Regarding IIEF scores of patients, there was no significant
difference between the two groups for different indicators. The vast majority of
men, 85%, report at least some difficulty with erections after prostate cancer
25 treatment [Emanu JC et al, 2016]. In the present study, it is observed that all five
indicators related to IIEF scores showed statistically significant improvement in the
patients. The use of this therapeutic technique in the management of sexual
functioning is supported by this research. Regarding urine-related problems, the
urine frequency significantly reduced from day 1 to day 90 in both treatment
30 groups. Earlier, Nassiri and Hosseinzadeh (2009) conducted a clinical trial on
46
prostate cancer patients and reported that after one month of administration of
nutraceutical supplements, there was a significant reduction in urine frequency.
In the study conducted by Agnihotri et al (2014), the prostate-specific antigen (PSA)
marker showed statistically non-significant change within and between groups. All
the patients had PSA levels below 5.82 ng/ml, which is the 5 cut-off referred for
biopsy. Although PSA measurement in the evaluation of BPH should not be a
requirement, its measurement before and after treatment may provide a surrogate
for treatment efficacy [Kim EH et al, 2016]. However, in the present study, there
was no effect of IP on the PSA levels of patients. Another study by Flaig et al.
10 (2010) suggests that herbal products and supplements with SOC do not show any
significant changes in PSA levels of patients. Other biochemical parameters
differed non-significantly within and between groups. Although some of the
hematological and vital parameters showed significant changes within the groups,
the change was clinically unrelated to the treatment. The adverse events were
15 smaller in the SOC+IP group as compared to the SOC group, eventhough the
difference was statistically non-significant (p=0.198).
References:
1. Chirumamilla MM. Prostate gland enlargement and ayurvedic treatment.
20 Available from:
http://www.muralimanohar.com/Articles,%20English/Prostate%20Gland%20Enla
rgement%20and%20Ayurvedic%20Treatment.html
2. Thakur, Shifali & Chaudhary, Gitika. (2021). Review Based Upon
Ayurvedic and Traditional Uses of Cinnamomum tamala (Tejpatta). International
25 Journal of Pharmaceutical Sciences Review and Research. 68.
10.47583/ijpsrr.2021.v68i02.011.
3. Planet Ayurveda. Effective prostate herbal remedies. Available from:
http://www.planetayurveda.com/prostateherbal-remedies.htm. [Last cited on 2012
May 15].
47
4. Clinical Efficacy Of Chandraprabha Vati In The Management Of Urinary
Tract Infection, Vd. Snehal S. Rachchawar, Vd. Geeta Parulkar, Vd. Dilip U.
Wange, International Journal Of Scientific Research, Volume – 12, Issue – 06, June
– 2023.
5. Macey MR, Raynor MC. Medical and 5 Surgical Treatment Modalities for
Lower Urinary Tract Symptoms in the Male Patient Secondary to Benign Prostatic
Hyperplasia: A Review. Semin Intervent Radiol. 2016 Sep;33(3):217-23. doi:
10.1055/s-0036-1586142. PMID: 27582609; PMCID: PMC5005076.
6. Ma, Xuesheng & Meredith, Juliana. (2021). Herbal medicine for the
10 treatment of andrological diseases: Traditional Chinese Medicine. 10.1016/B978-
0-12-815565-3.00020-5.
7. Bijak, M. Silybin, a major bioactive component of milk thistle (Silybum
marianum L.Gaernt.)-chemistry, bioavailability, and metabolism. Molecules. 2017:
22; 1942.
15 8. Alcaraz A, Carballido-Rodríguez J, Unda-Urzaiz M, Medina-López R.
Ruiz-Cerdá JL, RodríguezRubio F et al. Quality of life in patients with lower
urinary tract symptoms associated with BPH: change over time in real-life practice
according to treatment – the QUALIPROST study. Int Urol Nephrol. 2016: 48 (5);
645-656.
20 9. Patel HR, Patel M, Patel MM et al. Clinical evaluation of polyherbal formulation
in benign prostatic hyperplasia: randomized, placebo-controlled, single blinded
clinical study. International Journal of Clinical Trials. 2016: 3(3); 147-154.
10. Sahu M, Bhat R and Kulkarni K. Clinical evaluation of himplasia in benign
prostate hyperplasia: An open clinical trial. Medicine Update, 2003: 11 (1): 75-78.
25 11. Sokeland J. Combined sabal and urtica extract compared with finasteride in men
with benign prostate hyperplasia: analysis of prostate volume and therapeutic
outcome. BJU International. 2000: 86; 439-442.
12. Emanu JC, Avildsen IK and Nelson CJ. Erectile dysfunction after radical
prostatectomy: Prevalence, medical treatments and psychosocial interventions.
30 Curr Opin Support Palliat Care. 2016: 10(1); 102-107.
48
13.Nassiri M. and Hosseinzadeh, H , Review of the pharmacological effects of Vitis
vinifera (Grape) & its bioactive compounds. Phytother. Res. 2009: 23; 1197–1204.
14. Agnihotri S, Mittal RD, Kapoor R and Mandhani A. Raising the cut-off of
prostate specific antigen for biopsy in symptomatic men in India to reduce
5 unnecessary biopsies. Indian J Med Res.,2014: 139 (6); 851-856.
15. Kim EH, Larson JA and Andriole GL. Management of benign prostate
hyperplasia. Annual reviews. 2016: 67; 137-151.
16. Flaig TW, Glode M, Gustafson D, Bokhoven A, Tao Y, Wilson S et al. A study
of highdose oral silybin-phytosome followed by prostatectomy in patients with
10 localized prostate cancer. Prostate. 2010: 70; 848–855.Claims We claim
1. A polyherbo-mineral formulation comprising at least 14 herbal compositions selected from compositions of Achyranthes aspera (Apamarg), Boerhavia Diffusa (Punarnava: Hog Weed), Crataeva Nurvala (Varuna), Tribulus Terrestris (Gokshura or gokhru), Bauhinia Variegata (Kanchnaar Guggul), Zingiber Officinalis (Ginger), Piper Nigrum (Miri), Piper Longum (Piper), Terminala Chebula (black- or chebulic myrobalan), Terminalia Bellerica (baheda), Embelica Officinalis (Amalakki), Cinnamomum Tamala (Indian bay leaf), Elletaria, Cardamomum (green cardamom), Cinnamomum Zeylanicum, Hordeum Vulgare, Camphora Mukul, and at least one mineral composition of a mineral Zinc for Management Of Prostatic Disorders including treating Benign Prostrate Hyperplasia.
2. The polyherbo-mineral formulation as claimed in claim 1 comprising 16 herbal compositions selected from compositions of Achyranthes aspera (Apamarg), Boerhavia Diffusa (Punarnava: Hog Weed), Crataeva Nurvala (Varuna), Tribulus Terrestris (Gokshura or gokhru), Bauhinia Variegata (Kanchnaar Guggul), Zingiber Officinalis (Ginger), Piper Nigrum (Miri), Piper Longum (Piper), Terminala Chebula (black- or chebulic myrobalan), Terminalia Bellerica (baheda), Embelica Officinalis (Amalakki), Cinnamomum Tamala (Indian bay leaf), Elletaria, Cardamomum (green cardamom), Cinnamomum Zeylanicum, Hordeum Vulgare, Camphora Mukul, and at least one mineral composition of a mineral Zinc.
3. The polyherbo-mineral formulation as claimed in claim 2 comprising following compositions of herbal or mineral medicines; and excipients,

Ingredient % w/w of composition
1. Apamarg (Achyranthes aspera) Dry Extract / Kshara 1 – 10 %;
2. Kachnar bark (Bauhinia Variegata) dry extract 0.75 – 7.5 %;
3. Yashad Bhasma 1 – 10 %;
4. Guggul (Camphora Mukul) Dry Extract 1 – 10 %;
5. Tejpatta (Cinnamomum Tamala) Dry Extract 0.75 – 7.5 %;
6. Dalchini / Cinnamon (Cinnamomum Zeylanicum) Dry Extract 0.5 – 5.0 %
7. Varuna (Crataeva Nurvala) Dry Extract 5 – 15 %
8. Cardamon (Elletaria, Cardamomum) Dry Extract 1 – 10 %;
9. Amla (Embelica Officinalis) Dry extract 1 – 10 %;
10. Barley (Hordeum Vulgare)Dry Extract 5 – 25%
11. Pippali (Piper Longum) Dry Extract 0.5 – 5.0 %
12. Kali Mirch (Piper Nigrum) Dry Extract 1 – 10 %;
13. Baheda (Terminalia Bellerica) Dry Extract 1 – 10 %;
14. Harda (Terminala Chebula) Dry Extract 1 – 10 %;
15. Gokhru (Tribulus Terrestris) Dry Extract 0.75 – 7.5 %;
16. Saunth (Zingiber Officinalis) Dry Extract 1 – 10 %;
17. Punarnava (Boerhavia Diffusa) Dry Extract 1 – 10 %;
18. Excipients selected from one or more of diluent, binder, glidant, lubricant and disintegrant Up to 20 %, preferably up to 10 %.
4. The polyherbo-mineral formulation as claimed in claim 2 comprising in a single formulation, 16 herbal compositions and one mineral composition wherein each composition is in amount of not more than 200 mg.
5. The polyherbo-mineral formulation as claimed in claim 4 comprising in a single formulation, 16 herbal compositions and one mineral composition wherein each composition is in amount of not more than 100 mg.

6. The polyherbo-mineral formulation as claimed in claim 2 comprising in a single formulation, 16 herbal compositions and one mineral composition wherein each composition is in amount of from 10 mg – 70 mg.
7. The polyherbo-mineral formulation as claimed in claim 5 comprising in a single formulation, 16 herbal compositions and one mineral composition amounting not more than 1000 mg, preferably not more than 750 mg and more preferably not more than 600 mg.
8. The polyherbo-mineral formulation as claimed in claim 1 or 2 wherein herbal composition is a dry extract.
9. The polyherbo-mineral formulation as claimed in claim 1 or 2 wherein Apamarg composition is a dry extract or kshar.
10. The polyherbo-mineral formulation as claimed in claim 1 or 2 wherein composition of mineral zinc is a bhasma.
11. The polyherbo-mineral formulation as claimed in claim 1 or 2 wherein composition of Apamarg is kshar, composition of zinc is Bhasma and composition of each of Boerhavia Diffusa (Punarnava: Hog Weed), Crataeva Nurvala (Varuna), Tribulus Terrestris (Gokshura or gokhru), Bauhinia Variegata (Kanchnaar Guggul), Zingiber Officinalis (Ginger), Piper Nigrum (Miri), Piper Longum (Piper), Terminala Chebula (black- or chebulic myrobalan), Terminalia Bellerica (baheda), Embelica Officinalis (Amalakki), Cinnamomum Tamala (Indian bay leaf), Elletaria, Cardamomum (green cardamom), Cinnamomum Zeylanicum, Hordeum Vulgare, Camphora Mukul is a dry extract.
12. The polyherbo-mineral formulation as claimed in claim 2 containing excipients in an amount of from 0.1 – 20 % w/w of total weight of the formulation selected from a diluent, a binder, a glidant, a lubricant and optionally a disintegrant.
13. The polyherbo-mineral formulation as claimed in claim 2 containing from 0 – 15 % w/w, preferably from 0 – 10 % and more preferably from 1 – 5 % w/w of

a diluent, from 0.25 to 5 % w/w of a binder, and from 0.1 to 3 % w/w of lubricants and glidants and optionally a disintegrant in amount of up to 5 % w/w of the formulation.
14. The polyherbo-mineral formulation as claimed in claim 13 wherein diluent is selected from one or more of Starch, cellulose, lactose wherein Starch can be rice starch, potato starch, corn or maize starch or tapioca starch or any combination thereof, binder can be selected from starch paste, polyvinyl pyrrolidone, copovidone and hydroxy propyl methyl cellulose, glidants and lubricants are selected from Talc, colloidal silicon dioxide and magnesium stearate and a disintegrant when present is selected from starch, microcrystalline cellulose, sodium starch glycolate, crospovidone and croscaramellose sodium.
15. A process for preparing a polyherbo-mineral formulation comprising
i) dispensing dry extracts / dry extract powders of all ayurvedic medicines /
herbal medicines selected from Achyranthes aspera (Apamarg), Boerhavia Diffusa
(Punarnava: Hog Weed), Crataeva Nurvala (Varuna), Tribulus Terrestris (Gokshura
or gokhru), Bauhinia Variegata (Kanchnaar Guggul), Zingiber Officinalis (Ginger),
Piper Nigrum (Miri), Piper Longum (Piper), Terminala Chebula (black- or chebulic
myrobalan), Terminalia Bellerica (baheda), Embelica Officinalis (Amalakki),
Cinnamomum Tamala (Indian bay leaf), Elletaria, Cardamomum (green
cardamom), Cinnamomum Zeylanicum, Hordeum Vulgare, Camphora Mukul, or
dispensing dry extracts / dry extract powders of all herbal medicines except
Apamarg and dispensing kshar of Apamarg;
ii) dispensing Bhasma of zinc;
iii) optionally sifting dry extract powders / kshar / Bhasma if required;
iv) mixing all dry extract powders, kshar and Bhasma;
v) mixing blend of step iv with one or more excipients selected from diluent,
and binder, and if needed disintegrant to produce a blend;
vi) mixing blend of step v with glidant and / or lubricant and compress the blend
of step into tablets or filled into the capsules or sachets.;
or

vi) Granulating blend of step iv or v using water / solvent such as alcohol
selected from ethanol or isopropyl alcohol; or hydroalcoholic mixture or binder solution in water, alcohol or hydroalcoholic solvent in a mixer such as rapid mixer granulator wherein a binder is selected from starch, polyvinyl pyrrolidone, copovidone, hydroxy propyl methyl cellulose to obtain granules and blending granules with one or more excipients selected from diluent, binder, glidant and / or lubricant and if needed disintegrant to produce a blend;
vii) compressed blend into tablets or filled into the capsules or sachets;
viii) optionally coating the tablets.
16. The process as claimed in claim 15 wherein dry extract or dry extract powder
of herbal medicines is prepared by a process comprising
i) dispensing herbal medicine;
ii) grinding herbal medicine to produce coarse or fine powder;
iii) extracting ground powder with water or solvent preferably taking 3 times of
water or solvent compared to the ground powder;
iv) distilling extract to produce distillate;
v) drying distillate to produce dry powder;
vi) optionally grinding and sifting dry powder to produce dry extract powder of the
herbal medicine.
17. The process as claimed in claim 15 wherein kshar of Apamarg is prepared by a
process comprising
i) procuring dried apamarg and chopping into small pieces followed by further
drying chopped pieces under sunlight for up to 5 days (40 hours).
ii) Burning of dried Apamarga in a large iron pan where burning is continued till
white colour ash is obtained and leaving it for self-cooling (swangasheeta).
iii) Adding water in a ratio of (4,6 or 8) with 1 part ash and macerating well;
iv) Leaving the mixture undisturbed overnight for a period of 3 or 12 or 72 hours;
v) collecting supernatant by filtration and discarding dark colour sediment;
vi) obtaining clear liquid known as Ksharodaka (alkaline liquid) by filtering
supernatant 2 or 3 times;

vii). heating Ksharodaka (alkaline liquid) with moderate fire with alternating stirring for 3 hours till white colour powder is produced.
18. The process as claimed in claim 15 wherein Yashad bhasma is prepared by a three step process comprising Shodhan (purification), Jarana (polling) and Marana (incineration).
19. The polyherbo-mineral formulation of claim 2 for use in the Management Of Prostatic Disorders including treating Benign Prostrate Hyperplasia.

20. The polyherbo-mineral formulation of claim 2 for use in Management Of Prostatic Disorders including treating Benign Prostrate Hyperplasia in addition to standard of care treatment.
21. The polyherbo-mineral formulation of claim 2 for use in the treatment of Benign Prostrate Hyperplasia in addition to standard of care treatment (SOC) selected from one or more of the following,

Sr. No. SOC details Dose
1 Silodosin 8 mg/OD
2 Dutasteride 0.5 mg/OD
3 Alfuzosin 10 mg/OD
4 Tamsulosin (flowmax) 0.4 mg/OD
5 Bethanechol 50mg/OD
6 Mirabegron 50mg/OD
7 Tadalafil 5mg/OD
8 L-Arginine 6 gm SOS/OD
9 Proanthocyanidin 6.5 gm SOS/OD