natural herbal remedy for women health - ck ingredients presentation june... · 2018. 10. 31. · 2...

Naturalendo Tech Co., Ltd.

Natural Herbal Remedy for Women Health Novel Proprietary Standardized Healthcare Ingredient (EstroG-100)

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Corporate Overview

Establishment May 24, 2001 Employees 80 (22 R&D Employees)

IPO 31st Oct, 2013 in KOSDAQ / market capitalization is around USD 1.5 billion

Sales Revenue USD 124M in 2014 Capital USD 9.6M

Business Lines

1. Novel Proprietary Standardized Herbal Remedy (EstroG-100) 2. Immune Enhancer (Wellmune) 3. IGF-1 Secretagogue (YGF-251) 4. Cosmetic product (Micro Needle Patch): ENDODERMA (affiliated company)

Organizational Structure

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Healthcare Industry

Device & Equipment

U – Healthcare

Pharmaceutical

Nutraceutical

Cosmeceutical

Others Insurance

Health Machine

Hospital & Clinics

Novel Ingredient

Our Products

hGH Secretagogue

EstroG-100

Derma A2

TDDS

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Patents, Licenses, and Approvals • 17 registered and pending patents worldwide • Approved by U.S., Canada, Korea authorities

Health Canada NPN License

US FDA NDI

HFFI

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End Users • Clinically proven efficacy and safety: 1) Significant improvement of 10 menopausal symptoms out of 12 in total 2) Quality of Life improvement • Femoral Bone Mineral Density significantly improved • No side effects compared to other alternatives including HRT, Black Cohosh, and Isoflavone.

Market Status • Successful sales in Korea, US, Canada and expanding the market in other countries • Ranked No.1 over more than 45 products of HRT & Black cohosh since 2011 in Korea • Supplying to Korean major companies & its sales hit in retail price: 2010 USD 9M 2011 USD 55M 2012 USD 105M 2013 USD 270M 2014 USD 320M

“EstroG-100 is dominating the market by occupying over 90% market share of total menopause market in Korea (medicine + phytoestrogen)

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According to Health Claim, 10 Symptoms Improved!

• Date of License: July 5, 2011 • NPN(Natural Product Number): 80026169 • Helps to relieve the symptoms associated with menopause such as 1) Hot flashes 2) Night sweats 3) Paresthesia (numbness on hands/foot) 4) Insomnia 5) Nervousness 6) Melancholia(depression) 7) Vertigo(dizziness) 8) Fatigue 9) Rheumatic pain 10) vaginal dryness.

http://webprod3.hc-sc.gc.ca/lnhpd-bdpsnh/info.do?lang=eng&licence=80026169

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Risk Information: Cautions and Warnings Consult a health care practitioner if symptoms persist or worsen If you are taking ..any hormone-containing medication such as progesterone ..contraceptives or HRT or blood-thinning medication.. If you have liver troubles.

EstroG-100

10 specific claims with NO risk warning

Product A:

1 specific claim with Risk Warning

Risk Information:

None http://webprod3.hc-sc.gc.ca/lnhpd-bdpsnh/info.do?lang=eng&licence=80026169

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EstroG-100 is permitted as New Dietary Ingredient ※ The Federal Food, Drug, and Cosmetic Act (the act) requires that manufacturers and distributors who wish to market dietary supplements that contain “new dietary ingredients” which has not been distributed in USA market before 1994, notify the Food and Drug Administration about these ingredients. Generally, the notification must include information that is the basis on which manufacturers/ distributors have concluded that a dietary supplement containing a new dietary ingredient will reasonably be expected to be safe under the conditions of use recommended or suggested in the labeling. The NDI notification process is complex. NDI notifications are most often rejected due to insufficient evidence for safety, the absence of required elements, as well as lack of knowledge and experience for such notifications.

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• Approval No: 2010-20 • Claim: Help with climacteric women’s health ※ EstroG-100 is the first approved ingredient in Korea as Health Functional Food Ingredient by KFDA for alleviating menopausal symptoms such as hot flashes, night sweats, paresthesia(numbness on hand/foot), insomnia, nervousness, melancholia(depression), vertigo(dizziness), fatigue, rheumatic pain and vaginal dryness and formication

HFFI: Health Functional Food Ingredient

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2010 2050 2000

• Average Onset Age of Menopause is 49.7 in Korea • Estimated Menopause Population *32(22)% of Korean Women in 2000, raised to 45(30)% in 2010, and to 60(50)% in 2050 *32% = 10% of surgical and pre-mature menopause + 22% of natural menopause

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Function of Estrogen

• Growth and development of uterus and mammary gland • Expression of secondary sex characteristics • Control of menstrual cycles and supporting pregnancy • Bone metabolism and increase of BMD • Cardiovascular health and lipid metabolism • Anti-dementia, trophic factor for neuron • Colon cancer prevention • Teeth health • Prevention of macular degeneration • Fat distribution to subcutaneous fat tissue • Collagen production and maintaining human skin

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Menopause Classification

• About 8% Women (US) stop having period before age 40 • Same symptoms as Menopause • Average women go through this phase age 45~49 • Wildly fluctuating Estrogen Level • Same symptoms as Menopause • Estradiol level<50 pg/mL; FSH>50 mIU/mL; no period for >1 yr* • Average age for onset of menopause is 52 in US • Symptoms last 2~19 years, many more than 5 years • After Hysterectomy/Bilateral surgery * Definition: Dr. Joel Harglove, MD, Chairman, Vanderbilt Menopause Center, Nashville, TN

Premature Menopause Peri-menopause Menopause Surgical Menopause

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After Menopause, Women suffer….

• Hot flashes, Night sweats • Vaginal dryness & thinning of vaginal wall • Inelastic skin and dry eye, Insomnia, nervousness, depression, paresthesia(numbness), vertigo(dizziness), fatigue, rheumatic pain(joint), pounding of heart, headaches • Cardiovascular Diseases (CVD’s): 2 times higher risk of CVD’s after menopause • Osteoporosis

Physiological / Psychological Changes during Menopause Long Term Post-Menopause Health Risks

Women spend almost ½ of their lives post-menopause

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EstroG-100

• Herbal extracts screened out of 71 herbal extracts via non-reproductive tract target tissue response (E-screen test) • 3 herbal extracts were chosen: Cynanchum wilfordii, Phlomis umbrosa, and Angelica gigas Nakai

Proven Efficacy in vitro, in vivo, and in 3 human group (Asian and non-Asian) clinical studies

• About 400 years of documented use in Korea as folk medicine • Registered as safe main food ingredient in Korea Food Standard Codex • Cynanchum wilfordii & Phlomis umbrosa are reported to be liver-protective plants to WHO • No increase of uterus weight in ovariectomized rat tests • Inhibition of proliferation of human breast cancer cell (MCF-7) • No binding Affinity to both Estrogen Receptor α and β, cancer-inhibitory • Safe: Acute & Multi-dose toxicity tests , Genetic toxicity tests

Proven Safety

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Improving

menopausal

symptoms

Vaginal dryness

Hot flash/ Night sweats

Melancholia

Nervousness

Insomnia

Vertigo

Paresthesia

Fatigue

Rheumatic

pain

Formication

62% Improvement of symptoms

Efficacy of EstroG-100

• Clinically proven efficacy : 62% significant improvement of Quality of Life • 10 out of 12 climacteric symptoms significantly improved compared to Placebo

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Randomized Double-blind Placebo-controlled study (School of Medicine, Sungkyunkwan Univ. Samsung Cheil Hospital)

Dosing period 12 months (May 2003-April 2004)

Evaluation Style Long Term Safety Evaluation

Patients (n=47) 23 subjects in placebo group & 24 active group

Inclusion Criteria Age of 46 ~ 66 & Diagnosis of menopausal syndromes (average age=54)


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Climacteric Symptoms 5 times better improvement than placebo with significance

After 3 months OR=5.04 (95% C.I.=1.4-18.1) Fisher’s Exact Test

Femoral Bone Mineral Density Significant improvement

After 12 months 0.746±0.10 → 0.763±0.13 (P<0.05)

Serum hGH Level Significant improvement

After 12 months 0.25±0.21 → 0.92±0.97 (ng/mL) (P<0.05)

Serum Osteocalcin Level Significant improvement

After 12 months 6.02±2.74 → 5.66±3.01 (ng/mL) (P<0.05)

Serum Triglyceride Level Significant improvement

After 12 months 119.1±54.72 → 92.16±49.94 (mg/dL) (P=0.066)

Serum Alkaline Phosphatase Level Significant improvement

After 12 months 73.35±21.02 → 60.42±14.87 (IU/L) (P=0.08)


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Randomized, Double-blind, Placebo-controlled study (CA, USA)

Dosing period 3 months

Patients (n=61) 32 subjects in placebo group & 29 active group

Inclusion Criteria Age of 42 ~ 70 Diagnosis of menopausal syndromes(average age = 53)

Ad for Volunteers for US Clinical Study


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• Hot flush/ Night sweat • Paresthesia (numbness on hands/foot) • Vertigo (dizziness) • Fatigue • Muscular skeletal pain

• Nervousness • Insomnia • Depression • Formication


Kupperman Menopause Index and Vaginal Dryness (Difficulties in Sexual Intercourse) Improved Significantly

EstroG-100 was confirmed to improve both somatic and physiological symptoms with statistic significance.

Somatic / Physical Physiological / Psychological

Vaginal Dryness (Difficulties in Sexual Intercourse)

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EstroG-100 Mean±SE

Placebo Mean±SE

Week0 (Baseline) 1.45±1.02 1.75±1.11

Week6 (Change from baseline)

0.72±0.88 -0.72±0.84**††##

1.50±1.11 -0.25±0.57#


0.59±0.87 -0.86±0.88*##

1.28±1.02 -0.47±0.72## P=0.0536

SE: Standard Error *: Statistically significant compared between groups; p<0.05 by t–test(ITT) **: Statistically significant compared between groups; p<0.01 by t–test(ITT) ††; p<0.01 compared between groups by Wilcoxon rank sum test #; p-<0.05 compared to baseline, ##; p<0.01 compared to baseline by paired t-test

Fig. 1. Changes of vaginal dryness and reduced libido during 12 weeks administration of EstroG-100 and placebo.

Vaginal Dryness Improved Unlike Black Cohosh and Isoflavone

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Kupperman Index for Moderate or Severe Menopausal Symptoms Improved

SE: Standard Error **: Statistically significant compared between groups; p<0.01 by t–test(ITT) ††; p<0.01 compared between groups by Wilcoxon rank sum test ##; p<0.01 compared to baseline by paired t-test

EstroG-100 Mean±SE

Placebo Mean±SE

Week0 (Baseline) 29.45±7.39 29.16±6.55


13.62±7.61 -15.83±9.10**††##

23.31±8.96 -5.84±6.15##


11.31±5.78 -18.14±8.46**††##

23.66±7.68 -5.50±5.34##

Fig. 2. Changes of Kupperman Menopause Index(Mean±SE) during 12 weeks administration of EstroG-100 and placebo.

0

5

10

15

20

25

30

35

0 6 12

EstroG-100

Placebo

** **

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EstroG-100 (n=29) Placebo (n=32)

Week 0 Week 6 Week 12 Week 0 Week 6 Week 12

Vasomotor 2.24±0.69 1.03±0.82**††## 0.79±0.73**††## 2.22±0.66 1.78±0.75## 2.06±0.76

Numbness 1.31±0.85 0.59±0.78*†## 0.55±0.74*†## 1.41±0.91 1.13±0.94# 1.09±0.96##

Insomnia 2.28±0.84 1.28±0.96**†## 0.97±0.82**††## 2.03±0.86 1.63±1.01# 1.63±0.87#

Nervousness 1.72±0.88 0.76±0.69**††## 0.66±0.67**††## 1.56±0.84 1.22±0.83 1.34±0.75

Melancholia 1.93±0.88 1.03±0.68**††## 0.83±0.71**††## 1.59±0.95 1.31±0.93 1.31±0.74

Dizziness 0.97±0.82 0.21±0.49**††## 0.21±0.41**††## 0.75±0.72 0.72±0.77 0.59±0.80

Fatigue 2.21±0.77 0.90±0.77**††## 0.72±0.70**††## 2.00±0.88 1.69±0.90# 1.59±0.80#

Arthritic Pain 1.59±1.02 0.79±0.94**†## 0.55±0.78*†## 1.84±0.95 1.63±0.83 1.47±0.88

Headache 1.34±1.04 0.69±0.76## 0.66±0.77## 1.53±0.95 1.13±0.91# 0.84±0.72##

Palpitation (heart pounding) 1.00±0.96 0.48±0.69# 0.55±0.63# 1.31±0.93 0.91±0.82## 0.75±0.84##

Formication 0.83±0.85 0.14±0.44* ## 0.28±0.45## 1.25±1.05 0.88±1.01## 0.72±0.96##

*; p-<0.05 compared between groups, **; p<0.01 compared between groups by t –test †; p-<0.05 compared between groups, ††; p<0.01 compared between groups by Wilcoxon rank sum test, #; p-<0.05 compared to baseline, ##; p<0.01 compared to baseline by paired t-test

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Clinical Study III

Test Method Multi Center, Randomized double-blind placebo-controlled study

Study Location Aju University Medical Center Anam Hospital of Korea Univ. Severance Hospital of Yonsei Univ.

Test period 12 weeks

Dosage 638 mg tablet orally twice a day

Study Participants 96 female participants of age of 40~70 with menopausal symptoms (105 enrolled and 9 drop out)

Inclusion Criteria Age of 40 ~ 70 with menopausal symptoms

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The result almost duplicate the 2nd Clinical Study (Non-Asian) by improving as many as 9 different symptoms.

No significant differences or changes observed when measured endometrial thickness.

No change in weight, BMI, and the level of estrogen and FSH without any adverse event reported during the study. The endometrial thickness was measured to be observed not to change in addition.

Significantly Improved!

Hot flash

Paresthesia

Nervousness

Melancholia

Vertigo

Fatigue

Formication

Rheumatic pain

Vaginal Dryness

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KMI(Kupperman Menopause Index) Improved Significantly

Placebo N=47

Mean±SD

EstroG-100 N=49

Mean±SD

Week0 (Baseline) 32.89±7.75 35.14±8.11

Week4

(Change from baseline)

p-value**

24.72±9.48

-8.17±8.58

<0.01

23.20±9.25

-11.94±10.41

<0.01

<0.05

Week12


p-value**

20.35±10.31

-12.54±12.92

<0.01

14.84±9.94

-20.31±12.07

<0.01

<0.01

Fig. 1. Changes of Kupperman Menopause Index (Mean±SE) during 12 weeks administration of EstroG-100 and placebo. SE: Standard Error, *: Statistically significant compared between groups; p<0.05 **: Statistically significant compared between groups; p<0.01 by t–test(ITT)

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Vaginal Dryness(Difficulties in Sexual Intercourse) Improved Significantly

Placebo N=47

Mean±SD

EstroG-100 N=49

Mean±SD

Week0 (Baseline) 2.02±0.91 2.10±0.82

Week 4


p-value**

1.46±1.11

-0.57±1.15

<0.01

1.43±1.10

-0.67±0.94

<0.01

>0.05

Week 12


p-value**

1.48±1.05

-0.54±1.15

<0.01

1.10±1.12

-1.00±0.98

<0.01

<0.05

Fig. 2. Changes of vaginal dryness (Mean±SE) during 12 weeks administration of EstroG-100 and placebo. SE:Standard Error, *: Statistically significant compared between groups; p<0.05 by t–test

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In e-screen test, the estrogen-specific alkaline phosphatase has significantly increased and synergetic effects of EstroG-100 has been confirmed

• E-screen test: Screen herbal extracts for Estrogenicity • Synergetic Effects of 3 Constituent herbal extracts confirmed

- Lee at al., Lab. Anim. Res. 24(2): 167-172 (2008)

0

1

2

3

4

5

6

7

G1 G2 G3 G4 G5 G6 G7 G8 G9

Group

Os

teo

ca

lcin

(n

g/m

L)

* *

*

**

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

G1 G2 G3 G4 G5 G6 G7 G8 G9

GroupF

BM

D* (

g/㎠

)

** * *

**

**

-Kim at al., Kor. J Food Sci. Technol. 40(3): 316-320 (2008)

• Significantly improved in serum osteocalcin and FBMD in OVX rat • No change in weight, liver, kidney, and uterus weight in OVX rat

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• 75% higher satisfaction rate compared to the existing Isoflavone product • 69% picked “Better Efficacy” for the top reason for the higher satisfaction

- One month Open Label Clinical Study by Hiliving, the No.1 MLM firm among local capital MLM companies in Korea with 119 participants

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• 86% decrease in menopausal symptoms compared to 39% of the Isoflavone product • Sales volume increased 2.5 times, satisfaction/repurchasing/ recommendation rate soared

* One Month Open Label Clinical Study by Pulmuone Health Care with 31 participants

0%

20%

40%

60%

80%

100%

Isflavone EstroG-100

Satisfaction Rate

0%

50%

100%

150%

200%

250%


Sales Volume/Month

0

20

40

60

80


Repeat Order Rate

0%

20%

40%

60%

80%


Recommendation Rate

30


- One month Open Label Clinical Study by LG Household & Health Care for 6 weeks with 30 participants

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Hot flush and vaginal dryness, 33 % of total improved cases

- Open Label Clinical Study by Kim Jung Moon Aloe for 4 weeks with 20 participants

Symptoms cases %

Hot flush 11 20% Paresthesia 4 7%

Insomnia 3 6% Nervousness 3 6% Melancholia 3 6%

Vertigo 4 7% Fatigue 5 9%

Rheumatic pain 3 6% Formication 2 4% Headache 2 4% Palpitation 2 4%

Vaginal dryness 7 13% PMS 2 4%

Menstrual pain 2 4% Restarting menstruation 1 2%

Total 54 100%

Out of 20 participants, 10 participants showed the improvement of menopausal symptoms within 7 days after taking EstroG-100. The main improvement symptoms were hot flush and vaginal dryness, 33 % of total improved cases.

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Safety in three human clinical studies • No serious adverse effects – not even a single case of vaginal bleeding / spotting • No change in body weight • No significant changes in E2 and FSH • No change in blood pressure, blood sugar, cholesterol, LDL/HDL • No change in endometrial thickness

Other Proven features • All three herbs have been documented for use as herbal remedy for +400 years in Korea • All are registered as safe food ingredient in Korea Food Standard Codex • Cynanchum wilfordii & Phlomis umbrosa are reported to be liver-protective plants to WHO

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MCF-7 proliferation inhibition

Estrogen receptor binding affinity test

0 20 40 60 80

100 120

10㎍/㎖ 50㎍/㎖ 100㎍/㎖ 500㎍/㎖ 1000㎍/㎖

Cynanchum wilfodii extract P hlomis umbros a extrac t

0

20

40

60

80

10㎍/㎖ 50㎍/㎖ 100㎍/㎖ 500㎍/㎖ 1000㎍/㎖

EnBio Estrogen Receptor / Coactivator, Ligand Assay System

Affinity of EstroG to ER beta

10-6 10-5 10-4 10-3 10-2 10-1 100 101 102 103 104

0.0

0.3

0.6

0.9

1.2E2

FGF271

Concentration (ug/ml)

Ab

so

rb

an

ce (

450 n

m)

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• No specific toxic symptoms in relation to test substance were observed • Minimal lethal dose (MLD) > 4,000 mg/kg (HED = 648.6mg/kg)

• Ames (Bacterial Reverse Mutation), Micronucleus, Chromosome Aberration

• No observed adverse effect level (NOAEL): upward 1,000 mg/kg in the male and female group

Single oral toxicity study Thirteen-week repeated (91 day) oral dose toxicity study of in Sprague-Dawley rats Genetic Toxicity Study – proven non-toxicity

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a. E-screen assay to see non-reproductive tract target tissue response for a certain plant extract to induce alkaline phosphotase or ALP √ confirmed

b. Reproductive tract response for a certain plant extract to change uterus weight of ovariectomized rats (now, just for safety) √ confirmed

c. Receptor binding affinity test (now, just for safety) √ confirmed

d. Gene reporter vector assay (now, just for safety)

In a non-reproductive tract target tissue response for e-screen assay, all of the 3 constituent herbal extracts of EstroG-100 found to promote estrogen-specific ALP activity to show estrogenic action while EstroG-100 promoted more than any of the individual herbal extract (Lee et al. Anti-menopausal effect of the newly-developed phytoestrogen, FGF271 (=EstroG-100), in vitro and in vivo. Lab. Anim. Res. 24(2): 167-172(2008).) In the earlier study that has not been published, the 3 constituent herbal extracts of EstroG-100 were selected out of 71 different herbal extracts by this e-screen assay.

There are 4 different traditional methods of screening candidate plants for estrogenecity

EstroG-100 :

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Even though the exact mechanism has not been clarified, the following available evidences suggest that some phytochemicals in EstroG-100 act as estrogen agonists and/or antagonists without influencing the levels of estradiol (E2) and follicle stimulating hormone or (FSH):

In two researches for the reproductive tract target tissue response, EstroG-100 did not increase the uterus weight of ovariectomized rats while it increased femoral bone mineral density. (Kim et al. Korean J. Food Sci. Technol., 2008 and Lee et al. Lab. Anim. Res. 2008)

EstroG-100 did not show any affinity to both estrogen receptor alpha and beta in the receptor binding affinity test

reported by Chungbuk National Univ. of South Korea Each herbal extract of EstroG-100 showed inhibitory effect of the proliferation of human breast cancer (MCF-7) cells In a randomized double-blind placebo controlled clinical study, EstroG-200(A finished product containing EstroG-

100 as main active) improved menopausal symptoms, bone density of femoral bone neck, oseteocalcin level without any serious side effects with no increase of body weight and BMI and without influencing level of E2 and FSH (Lee et al. Evaluation of effectiveness and safety of natural plants extract (Estromon(=EstroG200)) on perimenopausal women for 1 year. J of Korean Society of Menopause. 11(1): 116-26 (2005)

In other clinical study performed in U.S. that was finished on Feb. 2010, EstroG-100 significantly improved

menopausal symptoms of non-Asian American women without any side effect (Chang et al. The Effect of Herbal Extract (EstroG-100®) on Pre-, Peri-, and Post-Menopausal Women: A Randomized Double-Blind Placebo-Controlled Study. Phytother. Res. 26: 510-516 (2012)).

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Various mechanism of action is being studied since there are number of somatic and psychological menopausal symptoms. The below is the summary of what’s been studied up to now.

Hot Flush: Ovariectomized (OVX) rat has been used as the animal model for menopausal hot flushes. Tail skin temperature (TST) has been monitored after challenge with pharmacological agents which can modulate thermoregulation pathway. Upon stress induced by dosing yohimbine and physical pressure, TST was measured with significant improvements in all EstroG-100 groups (125, 250 and 1000mg/kg/day) compared to control group after dosing 1 week.

Osteoarthritis: In vitro assay, levels of biomarkers related to healthy cartilage maintenance including type II collagen, aggrecan, sulfated proteoglycan and SOX-9 increased significantly and the inflammatory cytokine related biomarkers, COX-2, MMP, and NF-kB were evaluated to determine inhibition of arthritis, were significantly altered in EstroG-100 treated group (50ng/ml). In the in vivo carrageenan-induced paw edema model, the paw edema of the EstroG-100 treated groups (50, 100 and 200mg/kg/day) were inhibited similarly compared to cerecoxib treated group (60mg/kg/day).

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Osteoporosis - In vitro study, TRAP activation (osteoclast differentiation quantification factor) was

shown to be inhibited in dose-dependent manner in EstroG-100 treated groups (10mg/kg).

Sleep Disorder: EstroG-100 was administered once a day for 4 weeks (100 and 300mg/kg/day). At 30 minutes after the last administration, pentobarbital, the sleep inducer, was administered to measure the sleep induction time. Then sleep continuity time was measured upon the time of awakening in each testing group. Dosing of EstroG-100 decreased the sleep induction time and increased the sleep continuity time compared to control groups, which show that EstroG-100 has great benefits on sleep induction and sleep continuity.

Depression: EstroG-100 is confirmed to have antagonistic effects for 5-HT6 receptors (reported to be closely related to depression) in all concentrations, and it showed increased inhibition activity dose-dependently. Especially, 30 μg/mL dose showed 30~40% of inhibition activity, and 100 μg/mL dose showed more than 40% of inhibition. This result indicates that EstroG-100 has antagonistic effects to 5-HT6 receptors which could be effective as treatment of depression.

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• Women’s Health Initiative Study (WHI) • National Institute of Health (NIH) sponsored 8.5-year study with 16,000 subjects to estimate the benefits and risks of HRT • The Study was terminated early at 5 years with increased risks of breast cancer (26%), CVD (22%), stroke (41%), coronary heart disease (29%), blood clots (100%), Alzheimer's (100%) • US FDA required “Black Box Warning” • Prescribed ONLY for < 4 weeks

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-

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

5,000

'01 '03 '05 '07 '09 '11 '13E '15E '17E

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The U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) advised that a warning label would be placed on the all black cohosh products due to 21 reported cases of liver problems associated with black cohosh use (MHRA, 2006)

01/15/2007

At the end of one year, there was no significant difference seen between the number of daily hot flashes and/or night sweats in any of the herbal groups compared to the placebo group, with an average of 0.6 less vasomotor symptoms per day in the herbal groups. There was a significant difference-4.06 fewer symptoms per day-in the hormone therapy group compared to the placebo groups

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As of Oct 2012, due to 36 out of 53 case reports related to Black Cohosh involved liver problem, MHRA has warned manufacturers of Black Cohosh products that the herbal supplements must contain warnings about potential liver problems (MHRA 2012).

http://www.nutraingredients.com/Regulation/UK-tells-black-cohosh-makers-to-add-warnings-and-backs-THMPD

10/30/2012






















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Genistein (a major isoflavone aglycone) may cause Cancers ( NIH & FDA – National Toxicology Program, Genistein Final , Jan, 2008)

• Exposure to Genistein for 2 years caused mammary gland / pituitary gland adenoma in female rats. • Exposure to Genistein for shorter duration following birth was also possibly associated with increased rates of pituitary gland and mammary gland tumors.

Cancer Causing Risks

• Isoflavone Could be Toxic because its high level of hormone-like action. • It could be Hormone Dependent Cancer Causing Material due to its high binding affinity to Estrogen Receptor α, and β

Relative Binding Affinity

α β

Estradiol 100 100

Coumestrol1) 94 185

Genistein2) 4 87

1) Kuiper et al, Vol 139, No. 3, Endo 1997 2) Vol 138, No. 10, Endo 1998,

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EstroG-100 Pomegranate Soy Isoflavones Black Cohosh HRT

Improvement of Menopausal symptoms

10 1

(Hot Flush) 2

(Hot Flush, Fatigue) Partially some Improved

Improvement of

Vaginal Dryness O X X X O

Bone metabolism Index O X O X O

Bone density O

(FBMD) X O X

O

(Backbone)

Triglyceride O X X X X

Side Effect X X Cancer Related

(limit on dosage) Liver damage Fatal Side Effect

Increase of Body weight & BMI X X X X O

E2, FSH Changes X X X X O

Development In the 2000s In the 1998s In the 1990s In the 1990s In the 1940s

Related Patents 17 registered and pending X X X X

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Countries Category Authority Approval date / Expected date

15 2H 16 2H 17 1H 17 2H

USA Food supplement FDA Completed in 2010

Korea Health functional food

supplement MFDS Completed in 2010

Canada Natural health product Health Canada Completed in 2011

Malaysia Traditional medicine NPCB Completed in 2013

Pakistan Health supplement DRAP Completed in 2014

Thailand Food supplement MOPH Completed in 2014

India Food supplement FSSAI Competed in 2015

New Zealand Food supplement NZFSA Completed in 2015

Iran Food supplement MOHME Completed in 2015

EU Food supplement EFSA 3Q 2016 Expected Date

China Food supplement CFDA 3Q 2016 Expected Date

Japan Food supplement MHLW 3Q 2016 Expected Date

Ecuador Food supplement EMOH 1Q 2017 Expected Date

Vietnam Food supplement VFA 1Q 2017 Expected Date

Columbia Food supplement MHSP 1Q 2017 Expected Date

Dominica Food supplement DMOH 1Q 2017 Expected Date

Brazil Food supplement ANVISA 1Q 2017 Expected Date

Indonesia Food supplement BPOM 1Q 2017 Expected Date

Russia Food supplement MOPH 1Q 2017 Expected Date

Philippines Traditional medicine BFAD 1Q 2017 Expected Date

Egypt Food supplement EMOH 3Q 2017 Expected Date

46

BAEKSUO QUEEN (Lotte & CJ Home Shopping)

KT&G (Hwaaelak Queen)

NOWFOODS (Herbal Pause)

Donga BAEKSUO (Donga Pharm)

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Current Status in N. America Market

First bio company in Korea to receive the approvals and successfully signed the contracts to supply ingredients to major industries in North America.

Solidified contract with #1 Canadian Pharma Valeant

On the shelves of # 1 & 2 pharmacy chains, Walgreens & CVS

Major infomercial company Ideal Living launched Profemin

On the shelves of Whole Foods Market, the largest organic food supermarket

Solidified contract with Natural Factors, #1 health supplement company in Canada

Currently in negotiation with top 2-3 global pharmaceutical companies

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HERBALIFE Yakult CJO

https://en.wikipedia.org/wiki/File:LoblawsYongeAndBernard.JPG

natural herbal remedy for women health - ck ingredients presentation june... · 2018. 10. 31. · 2...

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