WO2018163192A1

WO2018163192A1 - Herbal extract for promoting and managing benign prostatic hypertrophy (bph) and related ageing symptoms using extract from ageratum spp.

Info

Publication number: WO2018163192A1
Application number: PCT/IN2018/000016
Authority: WO
Inventors: V.T. Jagannathan; R.V. Venkatesh
Original assignee: Jagannathan V T
Priority date: 2017-03-06
Filing date: 2018-03-06
Publication date: 2018-09-13
Also published as: WO2018163192A9

Abstract

An herbal extract and constituents for promoting and managing of BPH and related aging symptoms in male and addressing male health thereof using extracts from Ageratum spp.(including but not limited to Ageratum conyzoides, Ageratum coeruleum and Ageratum houstonianum). At least one compound of plants, ageratum spp. such as, N,N-bis(trimethylsilyI)-2-phenyl-7-(trifluoromethyl)quinolon-4-amine,3',4',5',6',7',8-hexamethoxyflavone, Phytol,Precocene, caryophyllene, squalene, alpha linolenic acid, 9,12-octadecadienoic acid (Z,Z)-,Hexadeconic acid and Hydrocoumarin can be extracted utilizing a Common Plant Extraction Approach (CPEA). The extraction of compounds can be performed utilizing an ethanol solvent and sterile water solvent and/or ethanol mixed with sterile water (i.e., hydro alcoholic solvents) separately and the concentrated materials obtained at both the solvents are pooled together (or separately) in order to obtain an herbal extract for promoting and managing of BPH.

Description

HERBAL EXTRACT FOR PROMOTING AND MANAGING BENIGN PROSTATIC HYPERTROPHY (BPH) AND RELATED AGEING SYMPTOMS USING EXTRACT

FROM A GERA TUM SPP.

TECHNICAL FIELD

[0001] Embodiments are generally related to field of pharmaceutics, medicine and allied industries. Embodiments are also related to herbal extraction processes and techniques. Embodiments are additionally related to herbal extracts and constituents for promoting and managing benign prostrate hypertrophy and related aging symptoms. Embodiments are particularly related to process for preparing a novel alleviating Benign Prostatic Hypertrophy (BHP) herbal extract using extract from Ageratum spp. (including but not limited to Ageratum conyzoides, Ageraium coeruleum and Ageratum houstonianum) for promoting and managing of Benign Prostrate Hypertrophy (BHP).

BACKGROUND OF THE INVENTION

[0002] Benign prostatic hyperplasia (BPH) is non-malignant enlargement of the prostate gland. BPH generally begins in a man's thirty's, evolves slowly, and most commonly only causes symptoms after 50. It is common in men age 50 and older with its prevalence being as high as 90% by 85 years of age (AUA, 2003). It may compress the urethra, which courses through the centre of the prostate. This can impede the flow of urine from the bladder through the urethra to the outside. It can cause urine to back up in the bladder (retention) leading to the need to urinate frequently during the day and night. Other common symptoms include a slow flow of urine, the need to urinate urgently and difficulty starting the urinary stream. More serious problems include urinary tract infections and complete blockage of the urethra. (Lepor et al, 2005).

[0003] The causes of BPH are not known. One theory is that, as men age, prostate cells accumulate di hydro testosterone (DHT) produced from testosterone via the enzyme alpha 5 reductase with a concomitant increase in estrogens through increased expression of aromatase which may promote growth factors such as epidermal growth factor and insulin-like growth factor, that lead to enlargement of the prostate. The currently available drugs used for the management of BPH are either a) alpha blockers relax the smooth muscles of the prostate, and the bladder neck, which helps to relieve urinary obstruction caused by an enlarged prostate in BPH, and b) 5- alpha reductase inhibitors block the conversion of the male hormone testosterone into its active form as DHT in the prostate. The prostate enlargement in BPH is thought to be directly dependent on DHT, so these drugs lead to an approximate 25% reduction in prostate size over six to 12 months. (Spatafora et al, 2012).

[0004] The most commonly available herbal medicines used in the management of BPH are Serenoa repensa, Pygeum africanum, Curcurbita pepo, Epilobim spp, Hyoxis rooperi,

Lycopersicum esculentum (tomato), Pinus pinaster, and Urtica dioico. (Allkanjan, & Vitalone

2015). A meta-analysis was conducted in 1998 analysingl 8controlled clinical studies showed the therapeutic efficacy of Serenoa repensa extracts to be significantly superior to placebo and identical to finasteride. Wiltetal, 1998) Pygeum africanum is an African herb used in many European prostate health products. It has also been the subject of a large number of separate clinical studies and has been found to stop night time urination and increasing the flow of urine during the day. (Allkanjari, & Vitalone 2015)

[0005] Ageratum conyzoides has a long history of use traditionally in Caribbean folk medicines (Lans 2007). The use of this species in traditional medicine is also extensive in regions including Brazil. Aqueous extracts of leaves or whole plants have been used to treat colic, colds and fevers, diarrhea, rheumatism, spasms, or as a urinary tonic. While there is little information on this herbal extract to date, it contains a wide variety of chemical compounds including that may have therapeutic activity including cumarins, (Vera, 1993) sterols ( amboj and Saluja, 20 1), flavonoids (Gonzalez et al, 1991). In a review of the pharmacological properties of Ageratum conyzoides, it was noted that 160 compounds have been identified and the crude fractions have shown multifarious pharmacological activities and have generally found to be safe. (Kauri & Dogra, 2014).

[0006] There is limited research on the use of extracts of plants and herbal medicines to improve male heath, particularly to help reduce the symptoms of BPH. There are no citations are literature which discusses use of extracts from Ageratum conyzoides for male health and symptoms associated BPH or with the age related decrease in androgens. However, having anti-inflammatory activity, anti-spasmodic activity and alpha 5 reductase enzyme inhibition, it is found to be a potential candidate therapy for BPH.

[0007] Based on the foregoing a need therefore exists for an improved process for preparing alleviating Benign Prostatic Hypertrophy (BHP) herbal extract using extract from Ageratum spp. (including, but not limited to, Ageratum conyzoides, Ageratum coeruleum and Ageratum houstonianum) for promoting and managing of Benign Prostrate Hypertrophy (BHP), as described in greater detail herein.

BRIEF SUMMARY

[0008] The following summary is provided to facilitate an understanding of some of the innovative features unique to the disclosed embodiment and is not intended to be a full description. A full appreciation of the various aspects of the embodiments disclosed herein can be gained by taking the entire specification, claims, drawings, and abstract as a whole.

[0009] It is, therefore, one aspect of the disclosed embodiments to provide for an improved herbal extract for promoting and managing of Benign Prostatic Hypertrophy (BPH).

[0010] It is another aspect of the disclosed embodiments to provide for an improved process for preparing herbal extract for promoting and managing of Benign Prostrate Hypertrophy

(BPH). [0011] It is f rther aspect of the disclosed embodiments to provide for an improved process for preparing a novel herbal extract using the aerial vegetative biomass (stem, leaf) of Ageratum conyzoides and its associated species for promoting and managing of Benign Prostatic Hypertrophy (BPH).

[0012] The aforementioned aspects and other objectives and advantages can now be achieved as described herein. An herbal extract and constituents for promoting and managing of BPH and related aging symptoms in male and addressing male health thereof using extracts from Ageratum spp. ^including but not limited to Ageratum conyzoides, Ageratum coeruleum and Ageratum houstonianum) is disclosed herein. At least one compound of plants, ageratum spp. such as, N-bisCtrimethylsily ^-phenyl-T-Ctrifluoromethy quinolon^-amine^'^'.S'^' '.S- hexamethoxyflavone, Phytol, Precocene, caryophyllene, squalene, alpha linolenic acid, 9,12- octadecadienoic acid (Z,Z)-,Hexadeconic acid and Hydrocoumarin can be extracted utilizing a Common Plant Extraction Approach (CPEA). The extraction of compounds can be performed utilizing an ethanol solvent and sterile water solvent and/or ethanol mixed with sterile water (i.e., hydro alcoholic solvents) separately and the concentrated materials obtained at these solvents systems are pooled together (or separately) in order to obtain an herbal extract for the treatment of BPH.

[0013] The composition proposed herein comprises following compounds which plays a vital role in promoting and managing prostate health that is free from alkaloids: T- cadinene compound inhibits the growth of cancer cells. Encecaline-1- (7-methoxy2- 2-dimethyl- 2h- chromen- 6yl)ethanone of the composition prevents cancer. Senensetin=5,6,7_s3,4-pentamethoxy flavone acts as an antiinfl amatory and anticancer. Nobiletin=3_J4_J5,6,7,8-hexamethoxyflavone acts as anticancer invasion. Beta selinene acts as Anti-inflammatory and cancer prevention. Stigmastero! and Sitosterol prevents the prostate cancer. Beta-sttosterol blocks the production of dihydrotestosterone. Quercetin=3\3',4\5-7 pentahydroxy flavone used for prostitis health. Rutin=Quercetin-3- o-rhamnosylglucoside demonstrates anticancer activity and Coumarine=2H- 1- benzopyran-2- one demonstrates antitumour activity. Endo-borneol acts as anti-inflammation and Farnesol acts as a precursor for sterol biosynthesis. 6,7-dimethoxy- 2-2- dimethylchromene=Precocene Π- acts as antiinflamatory, antitumour and anticancer. Hexadecenoic acid=2-palmitoleic acid, palmitic acid and Linoleic acid=Omega-6 fatty acids ,(9z,12z)-Octadeca- 9,12-dionoic acid involved in biosynthesis of prostaglandin. Caryophyllene acts as anticarcinogenic and anti-inflammatory. Squalene acts as antitumour and anticancer and increases immune functions. Phytol=3',4\5.6,7,8-hexamethoxyflavone brings stronger immune system, maintaining cell health and decreasing cell ageing. Alpha linolenicacid reduces inflammation and prevent cancer. Conyzorigin acts as anticancer. The above composition obtained from the extraction of Ageratum spp. can be a novel composition demonstrating enhanced promotion and management of prostate health. Please note that the extraction technique and composition forming plays a vital role in developing the compound.

[0014] The common Plant Extraction Approach (CPEA) described herein can be a principle extraction technique that is well known in the art for extracting the compounds of a plant.

Initially, the aerial vegetative biomass of Ageratum spp. (preferably 60 to 90 days old plants) can be sliced into pieces (approx. l inch size) and dried at open sunlight (3-4 hours) for the removal of the moister or water content attached with the aerial biomass and subsequently shade dried at room temperature. The sliced pieces can be also dried using a fluid flash dryer. Further, a mechanized pulverizing machine can be employed to grind the dried plant slices into coarse powder in order to thereby extract the compounds using the ethanol and sterile water and ethanol mixed with sterile water solvents separately. The solvent extraction process described herein can be performed at a 1 : 10 (W/V) ratio using a Soxhlet apparatus for ethanol extraction and sterile water extraction separately and /or mixing of ethanol and water extraction and thereby the solvents separated from the extracts using a rotary evaporator under reduced pressure.

[0015] The compounds obtained at both the ethanol solvent extraction process and the sterile water solvent extraction process and mixing of ethanol and water extraction process are further pooled together (or used separately) in order to form the herbal extract for treating the BPH and its related ageing issues in male. The compounds extracted at the aqueous and hydro alcoholic extraction process can be such as, for example, but not limited to, Quercetin-3-O- rhamnopyranoside, quercetin-3,7-diglucopyranoside, /'-Hydroxy benzoic acid, N,N- bis(trimethylsilyl)-2-phenyl-7-(trifluoromethyl)quinolon-4-amine,l-deoxy-d-manitol, 15- hydroxypentadecanoic acid, 2-chromenone, 3',4\5\6',7',8-hexamethoxyflavone,3,5-di-tert- butylbenzoic acid, 3- phenylisoquinoline, 3,7,1 l ,15-tetramethylhexadec-2-en-l-ol, 4-tert-butyl- 2,6-dimethylacetophenone, 6-vinyl-7-methoxy-2,2-dimethylchromene,Androhydro-d-mannosan, beta-Funebrene, caryophyllene, coumarin, hexxa-o-methylmyricitin, hydrocoumarin, linoleoyl chloride, methyl cis-1 1, 14,17-icosatrienoate, methyl linoleate, Neophytadiene, p- Octylacetophenone, phenol, 2,4,6-tris (IJ-dimethylethyl), phytol, precocene I and II,squalene, and beta sitosterol. [0016] The compounds extracted at the ethanol solvent extraction process can be such as, for example, but not limited to, N,N-bis(trimethylsilyl)-2-phenyl-7-(trifluoromethyl)quinolon-4- amine, (Z)-3eta-famesense, l-(3,5-ditert-butyle-4-hydroxyphenyl)ethanone, 2-(l ,3- benzodioxol-5-yl)-5-hydroxy-3,6,7,8-tetramethoxy-4h-chromen-4-one,2-(3,4-dimethoxyphenyl)- 5,6,7,8-tetramethoxy-4H-l-benzopyran-4-one, 2,4,6-tri-tert-butylphenol, 2-chromanone, 2H- chromen-2-one, 3',4'5,,6,7,8-hexamethoxyflavone, 3,5-di-tert-butylbenzoic acid, 3,7,11 ,15- tetramethylhexadec-2-en-l -ol, 3-thujanol, 4-tert-butyl-2,6-dimethylacetophenone, 6- demethoxyageratochromene, 6-vinyl-7-methoxy-2,2-dimethylchromene, 9,12-octadecadienoic acid (Z,Z)-,AJl-trans-squalene, Alpha-benzopyrone, Alpha-caryophyllene, Alpha-linolenic acid, Alpha tocopherol -be ta-D-m an noside, Beta-sesquiphellandrene, Butylphosphonic acid, hexyl 4- (2-phenylprop-2-yl)phenyl ester, Caryophyllene, Coumarin, Delta-cadi nene, Dotriacontane, Hexadeconoic acid, hydrocoumarin, methyl cis-1 1, 14, 17-icosatrienoate, methyl linoleate, methyl palmitate, neophytadiene, N-hexatriacontane, n-tetracontane, N-tetracosane, N-tetratriacontane, N-triacontane, Phytol, precocene I, Precocene II, squalene, stigmasterol, Stimasta-4,2,2-dien- 3,beta-ol, and Tetracontane. The solvents utilized for extracting compound herein should not be construed in any limited sense. Those skilled in the art can understand that similar kind of solvents such as hexane, ethyle acetate, acetone, chloroform, dichloromethane, etc. can also tried for preparing herbal extraction and developing the formulation for the treatment of BPH.

DETAILED DESCRIPTION

[0017] The particular values and configurations discussed in these non-limiting examples can be varied and are cited merely to illustrate at least one embodiment and are not intended to limit the scope thereof [0018] The embodiments now will be described more fully hereinafter with reference to the accompanying drawings, in which illustrative embodiments of the invention are shown. The embodiments disclosed herein can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like numbers refer to like elements throughout. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

[0019] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and/or "comprising," when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[0020] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0021] An herbal extract and constituents for promotion and management of BPH and related aging symptoms in male and addressing male health thereof using extracts from Ageratum spp. (Including but not limited to Ageratum conyzoides, Ageratum coeruleum and Ageratum houstonianum) is disclosed herein. At least one compound of plants, ageratum spp. such as, N,N-bis(trime lsilyI)-2-phenyl-7-(rrifl^

hexamethoxyfiavone, Phytol, Precocene, caryophyllene, squalene, alpha linolenic acid, 9,12- octadecadienoic acid (Z,Z)-,Hexadeconic acid and Hydrocoumarin can be extracted utilizing a Common Plant Extraction Approach (CPEA). The extraction of compounds can be performed utilizing an ethanol solvent and sterile water solvent and/or ethanol mixed with sterile water (i.e., hydro alcoholic solvents) separately and the concentrated materials obtained at both the solvents are pooled together (or separately) in order to obtain an herbal extract for promoting and managing of BPH.

[0022] The composition proposed herein comprises following compounds which plays a vital role in promoting and managing prostate health that is free from alkaloids: T- cadinene compound inhibits the growth of cancer cells. Encecaline-1- (7-methoxy2- 2-dimethyl- 2h- chromen- 6yl)ethanone of the composition prevents cancer. Senensetin=5,6,7,3,4-pentamethoxy flavone acts as an antiinf!amatory and anticancer. Nobiletin=3,4,5,6,7,8-hexamethoxyflavone acts as anticancer invasion. Beta selinene acts as Anti-inflammatory and cancer prevention. Stigmasterol and Sitosterol prevents the prostate cancer. Beta-si tosterol blocks the production of dihydrotestosterone. Quercetin=3',3',4'₃5-7 pentahydroxy flavone used for prostitis health. Rutin=Quercetin-3- o-rhamnosylglucoside demonstrates anticancer activity and Coumarine=2H- 1- benzopyran-2- one demonstrates antitumour activity. Endo-borneol acts as anti-inflammation and Farnesol acts as a precursor for sterol biosynthesis. 6,7-dimethoxy- 2-2- dimethylchromene=Precocene II- acts as antiinflamatory, antitumour and anticancer. Hexadecenoic acid=2-palmitoleic acid, palmitic acid and Linoleic acid=Omega-6 fatty acids ,(9z,l 2z)-Octadeca- 9, 12-dionoic acid involved in biosynthesis of prostaglandin. Caryophyllene acts as anticarcinogenic and anti-inflammatory. Squalene acts as antitumour and anticancer and increases immune functions. Phytol=3',4',5.6,7,8-hexamethoxyflavone brings stronger immune system, maintaining cell health and decreasing cell ageing. Alpha linolenicacid reduces inflammation and prevent cancer. Conyzorigin acts as anticancer. The above composition obtained from the extraction of Ageratum spp. can be a novel composition demonstrating enhanced promotion and management of prostate health. Please note that the extraction technique and composition forming plays a vital role in developing the compound.

[0023] The common Plant Extraction Approach (CPEA) described herein can be a principle extraction technique that is well known in the art for extracting the compounds of a plant.

[0024] The compounds obtained at both the ethanol solvent extraction process and the sterile water solvent extraction process and mixing of ethanol and water extraction process are further pooled together (or used separately) in order to form the herbal extract for treating the BPH and its related ageing issues in male. The compounds extracted at the aqueous and hydro alcoholic extraction process can be such as, for example, but not limited to, Quercetin-3-O- rhamnopyranoside, quercetin-3,7-diglucopyranoside, f-Hydroxy benzoic acid, N,N- bis(trimethylsilyl)-2-phenyl-7-(trifluoromethyl)quinolon-4-amine,l -deoxy-d-manitol, 15- hydroxypentadecanoic acid, 2-chromenone, 3\4\5\6\7\8-hexamethoxyflavone,3,5-di-tert- butylbenzoic acid, 3- phenyl isoquinoline, 3,7,11 ,15-tetramethylhexadec-2-en-l -ol, 4-tert-butyl- 2,6-dimethylacetophenone, 6-vinyI-7-methoxy-2,2-dimethylchromene_rAndrohydro-d-mannosan, beta-Funebrene, caryophyllene, coumarin, hexxa-o-methylmyricitin, hydrocoumarin, linoleoyl chloride, methyl cis-1 1,14,17-icosatrienoate, methyl linoleate, Neophytadiene, p- Octylacetophenone, phenol, 2,4,6-tris (1,1-dimethyIethyl), phytol, precocene I and n,squalene, and beta sitosterol.

[0025] The compounds extracted at the ethanol solvent extraction process can be such as, for example, but not limited to, N,N-bis(trimethylsilyl)-2-phenyI-7-(trifluoromethyl)quinolon-4- amine, (Z)-,Beta-famesense, l -(3,5-ditert-butyle-4-hydroxyphenyl)ethanone, 2-(l,3- benzodioxol-S-ylJ-S-hydroxy-S^^^-tetramethoxy^h-chromen^-one^-iS^-dimethoxyphenyl)- 5,6,7,8-tetramethoxy-4H-l -benzopyran-4-one, 2,4,6-tri-tert-butyIphenol, 2-chromanone, 2H- chromen-2-one, 3',4'5,,6,7,8-hexamethoxyfIavone, 3,5-di-tert-butylbenzoic acid, 3,7,1 1,15- tetramethylhexadec-2-en-l -ol, 3-thujanol, 4-tert-butyl-2,6-dimethylacetophenone, 6- demethoxyageratochromene, 6-vinyl-7-methoxy-2,2-dimethylchromene, 9,12-octadecadienoic acid (Z,Z)-,All-trans-squalene, Alpha-benzopyrone, Alpha-caryophyllene, AJpha-linolenic acid, Alpha tocopherol-beta-D-mannoside, Beta-sesquiphellandrene, Butyl phosphonic acid, hexyl 4- (2-phenylprop-2-yl)phenyl ester, Caryophyllene, Coumarin, Delta-cadinene, Dotriacontane, Hexadeconoic acid, hydrocoumarin, methyl cis-1 1,14,17-icosatrienoate, methyl linoleate, methyl palmitate, neophytadiene, N-hexatriacontane, n-tetracontane, N-tetracosane, N-tetratriacontane, N-triacontane, Phytol, precocene I, Precocene II, squalene, stigmasterol, Stimasta-4,2,2-dien- 3,beta-ol, and Tetracontane.

[0026] The solvents utilized for extracting compound herein should not be construed in any limited sense. Those skilled in the art can understand that similar kind of solvents such as hexane, ethyle acetate, acetone, chloroform, dichloromethane, etc. can also tried for preparing herbal extraction and developing the formulation for the treatment of BPH.

[0027] In vitro study on the evaluation of activity modulation of 5 alpha reductase type 1 and type 2 gene expression profiles on human prostrate cells using the extract of Ageratum spp. was conducted. The extract produced very good amount of reduction (2.6 times) of the activity of the enzyme ensuring the efficacy of the herbal extract of ageratum spp. in reducing the symptoms of BPH.

[0028] In vitro methods of study are interesting alternative system to traditional in vivo tests to evaluate biological properties of ingredients or finished products for biomedical employ. The aim of the study is to find out and quantify the changing in the expression level of 5 alpha reductase in human prostrate cells. The enzyme is expressed in skin melanocytes, fibroblasts and keratinocytes and transforms testosterone into dihydrotestosterone, a key metabolite implicated in various biological functioning. After birth the 5 alpha reductase (typel) is expressed in more locations, including the liver, skin, scalp and prostrate. 5 alpha reductase (Type 2) is expressed in prostrate, seminal vesicles, epididymis liver, and to a lesser extent the scalp and skin.

[0029] In this in vitro test fibroblasts are pre-treated with testosterone in order to induce the production of 5 alpha reductase and are exposed subsequently to the various test substances for 48 hours. A titrated extract of Serenoa repens (Saw palmetto), a well known pharmacologically active compound used to treat the prostrate hyperplasia is used as a positive control.

[0030] Clinical trial was conducted with the herhal extract of ageratum spp. on the human prostrate cells for a short duration of 12 weeks period in Brisbane, Australia and accessed efficacy of the herhal extract made out of Ageratum spp. on the symptoms of BPH, associated aging-related symptoms and changes in PSA levels, sex hormones, lipids and blood sugar levels in middle aged and older males and found to be very successful in treating BPH.

[0031] In the above mentioned clinical trial the efficacy of the herhal extract of Ageratum spp. was assessed mainly for the primary symptoms of Benign Prostrate Hypertrophy (BPH) using the International Prostrate Symptom Score (IPSS), which includes assessment of the quality of life. The secondary outcome of measurement on aging related symptoms using the Aging Male Symptoms (AMS) questionnaire including questions on psychological, somatic and sexual. In both the cases the subjects were completed on the questionnaires of pre-trial (baseline data) and data on 4,8 and 12 weeks.

[0032] Initially, 106 men were enrolled and commenced treatment in the study, with 98 completing the study; 52 in the active treatment group and 46 in the placebo group. There were eight withdrawals from the study; three from active treatment group; five from placebo group. There were no significant differences between the active treatment and placebo groups for average age, anthropometric measures and the lifestyle factors. The sex hormone profiles were similar between both groups, as was total cholesterol, triglycerides and blood glucose levels. The study cohort had normal full blood count, renal and liver function parameters. The average PSA levels were similar in both groups at baseline as a total cohort and also when stratified for age, (using the individual healthy reference ranges for men aged <50, >50<60, >60<70 and those men >70 years of age).

[0033] Relationship between age and health indices age was significantly positively correlated with PSA levels in both groups (Active treatment group, r=0.250, p=0.01; Placebo group r=0.237, p=0.03).

There was no correlation between age and severity of symptoms at any time point as measured by the IPSS in either group (Active treatment group, r=0.037, p=0.72;

Placebo group r=0.048, p=0.64). There was no correlation between PSA levels and either total testosterone or free testosterone or oestradiol, Cortisol, DHEA, SGBP or blood glucose in either group. Age was not correlated with total testosterone in either group however, free testosterone was negatively correlated with age in the active group (r=206,p=0.04) and placebo group (r=0.208, p=0.5). In both groups, at baseline, BM1 positively correlated with both total testosterone levels (active treatment, r=0.429, <0.0 l ; placebo group, r=0.35, p+<0.001).

[0034] There was no change in general health parameters; including weight or blood pressure during the study for either the active treatment or placebo group. There were no significant changes in lifestyle including sleep patterns, the type or duration of physical activity in either group.

[0035] There was no significant difference between the groups at baseline. The average IPSS score for active treatment and placebo groups respectively were 22.0 and 20.0, considered to be in "severely symptomatic". There was a gradual significant reduction in IPSS over time in the active treatment group from a score of 22.0 to 15.1 , considered to be "moderately symptomatic". The IPSS score remained relatively stable at all time points in the placebo group. Repeated measures ANOVA showed a significant difference across time F( 1,406) = 12.72, P<0.001 and a significant difference between groups F(l ,1508) = 47.23, P=0.001 for total IPSS Score.

[0036] In the Active treatment group, there was a steady reduction in the symptom severity for all questions in the IPSS at TW4 and then at TW8 and this effect was maintained at TW12. There were no changes observed in the average responses of the placebo group. The night time urinary frequency was reported in question seven; this reduced from 2.5 - 1.7 in the Active treatment group but remained relatively constant in the placebo group (2.2 to 2.4). At baseline, the average quality of life response (question eight) was four (Mostly unhappy about the condition) for both groups. There was a slight improvement in the Active treatment group who reported an average score of three (Mixed feelings about the condition) after the treatment period.

[0037] The average day-time and night-time urinary frequency for the active treatment and placebo treatment groups at TWO were similar at baseline, and reflected a total daily urinary frequency of approximately nine times per day. For most people, normal frequency is about six to seven times in a 24-hour period. There was a steady decrease in both day-time frequency and night-time frequency in the active treatment group observed at TW4 and this continued at TW8 and TW12. The total frequency in the Active treatment group significantly reduced from 9.2 to 6.9 time per day over the treatment. There was no change in day-time or night-time urinary frequency in the placebo group. This resulted in a significant difference between groups for day-time frequency (W = 1827, p- value = 7.167e-06) and nighttime frequency (W = 1999, p- value = 1 ,015e-08).

[0038] The severity of the aging-related symptoms, often attributed to andropause and low testosterone, was assessed using the AMS questionnaire at TWO and TW12. Both the active treatment and placebo groups had the same symptom severity at commencement of treatment. There was a no change in totaJ AMS score or the psychological, somatic or sexual sub-domains in either the active treatment group or the placebo group at TWO, which is consistent with the no changes observed in total and free testosterone levels.

[0039] Effect on Hormones, Cholesterol, Triglycerides and PSA The androgens, total testosterone, free testosterone, androstenedione and DHT as well as SHBG were in the healthy reference range for both groups and remained stable over the 12 weeks. There were no changes in Cortisol or DHEA levels in either group. Total cholesterol and triglycerides remained stable over the treatment in both groups. The average PSA levels did not change in either Active treatment or placebo group after treatment.

[0040] The effect of Ageratum conyzoides on sexual function was assessed using the DISFSR at baseline and at week 12 for those men that chose to answer the questionnaires. There was no significant change in the total score or the sub-domain scores in active treatment group after treatment. There were no changes observed in the placebo group before or after treatment in total score or any sub-domain.

[0041] The Clinical trial conducted with the herbal extract of Ageratum spp. on the prostrate ceils was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) with Trial ID. ACTRN No: 12614001074684. The study was carried out according to the principles expressed in the Declaration of Helsinki and was approved by the Queensland Clinical Trial Network Human Research Ethics Committee (QCTN) No: 2014001.

[0042] It will be appreciated that variations of the above-disclosed and other features and functions, or alternatives thereof, may be desirably combined into many other different systems or applications. Also that various presently unforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art which are also intended to be encompassed by the following claims.

Claims

CLAIMS lAVe Claim:

1. A process for preparing herbal extract and constituents for promotion and management of Benign Prostatic Hypertrophy (BPH) and related aging symptoms in male and addressing male health thereof using extracts from Ageratum spp., said process comprising:

extracting at least one compound of Ageratum spp. utilizing an ethanol solvent and sterile water solvent and/or ethanol mixed with hydro alcoholic solvents separately and the concentrated materials obtained at both the solvents are pooled together in order to obtain an herbal extract which plays a vital role in promoting and managing prostate health that is free from alkaloids.

2. The process of claim 1 wherein at least one compound of Ageratum spp. comprises at least one of the following compounds: N_JN-bis(trirnethylsilyl)-2-phenyl-7-(trifluoromethyl)quinolon- 4-amine,3\4\5',6',7',8-hexamethoxyflavone, Phytol, Precocene, caryophyl!ene, squalene, alpha linolenic acid, 9,12-octadecadienoic acid (Z_jZ^Hexadeconic acid and Hydrocoumarin.

3. The process of claim 2 wherein the extraction of compounds can be performed utilizing an ethanol solvent and sterile water solvent and/or ethanol mixed with hydro alcoholic solvents separately and the concentrated materials obtained at both the solvents are pooled together in order to obtain an herbal extract which plays a vital role in promoting and managing prostate health that is free from alkaloids.

4. The process of claim 1 wherein the composition comprises T- cadinene compound which inhibits the growth of cancer cells.

5. The process of claim 1 wherein the composition comprises Encecaline-1- (7-methoxy2- 2- di methyl- 2h-chromen- 6yl) ethanone which prevents cancer.

6. The process of claim 1 wherein the composition comprises Senensetin-5,6,7,3,4- pentamethoxy fiavone that acts as an anti-inflammatory and anticancer.

7. The process of claim 1 wherein the composition comprises Nobiletin-3,4,5,6,7,8- hexamethoxyflavone which acts as anticancer invasion.

8. The process of claim 1 wherein the composition comprises Beta selinene which acts as Antiinflammatory and cancer prevention.

9. The process of claim 1 wherein the composition comprises Stigmasterol and Sitosterol which prevents the prostate cancer.

10. The process of claim 1 wherein the composition comprises Beta-sitosterol which blocks the production of dihydrotestosterone.

1 1. The process of claim 1 wherein the composition comprises Quercetin=3',3',4',5-7 pentahydroxy fiavone used for promoting and managing prostitis health.

12. The process of claim 1 wherein the composition comprises Rutin=Quercetin-3- o- rhamnosylglucoside which demonstrates anticancer activity and Coumarine=2H-l - benzopyran- 2- one which demonstrates anti-tumour activity.

13. The process of claim 1 wherein the composition comprises Endo-borneol which acts as anti- inflammation and Farnesol which acts as a precursor for sterol biosynthesis.

14. The process of claim I wherein the composition comprises 6,7-dimethoxy- 2-2- dimethylchromene=Precocene Π- that acts as an tiinfl amatory, antitumour and anticancer.

15. The process of claim 1 wherein the composition comprises Hexadecenoic acid=2- palmitoleic acid, palmitic acid and Linoleic acid=Omega-6 fatty acids,(9z,l 2z)-Octadeca- 9,12- dionoic acid which involves in biosynthesis of prostaglandin.

16. The process of claim 1 wherein the composition comprising Caryophyllene which acts as anticarcinogenic and anti-inflammatory.

17. The process of claim 1 wherein the composition comprises Squalene which acts as anti tumour and anticancer and increases immune functions.

18. The process of claim 1 wherein the composition comprises Phytol=3',4',5.6,7,8- hexamethoxyflavone which brings stronger immune system, maintaining cell health and decreasing cell ageing.

19. The process of claim 1 wherein the composition comprises Alpha linolenicacid reduces inflammation and prevent cancer.

20. The process of claim 1 wherein the composition comprises Conyzorigin which acts as anticancer.