B2E-PHYSICIANS SCIENCE TRIFOLD ENG

The Ethocyn Molecule
ELASTIN: THE YOUTH PROTEIN
Your skin is comprised of collagen and elastin fibers. Collagen fibers [found in the
reticular dermis] are the structural fibers of the skin. Collagen fibers do not
stretch very well. In fact, one of its functions if to resist stretching and provide
structure. Scar tissue is composed of collagen fibers, for example. Elastin fibers
[found in the papillary dermis] are recognized by leading academic dermatologists to be the important “Youth Protein” fibers of skin. Skin elastin fibers are
what gives youthful, smooth, firm skin its resiliency - its retraction and “snap.”
Elastin fibers are considered the skin’s “rubberbands.”
IUPAC: 6-(5-ethoxyheptyl-1-yl) bicyclo[3.3.0]octan-3-one
(CH2)4 CHCH3
Tradename: Ethocyn
Chemical Properties: racemate compound; 4 chiral centers;
8 isomers/enantiomers (stable cis bridge)
OCH2CH3
Physical Properties: clear, colorless oil
A topical, safe, and efficacious, non-steroidal anti-androgen. A noninvasive, non-irritating, unique and intelligent serum for skin aging.
Synthesis: 11-step organic synthesis + HPLC purification
Patents: Series I: Racemate structures: Composition of Matter,
Process, and Use patents issued
Medical research findings confirm that our skin
produces/synthesizes less and less elastin fibers as we
chronologically age. This is recognized to be Intrinsic
Skin Aging and completely independent of Photo (sun)
Damage Skin Aging. Using sun screens and sun blocks
protect skin from Photo Skin Aging. Using Ethocyn by
chanTal skin care products treats Intrinsic Skin Aging.
Elastin fibers give skin its ‘rubberband, snap-back’
quality. Sagging skin is lacking in ‘youth levels’ of elastin
rubberband fibers. Wrinkles form because there is elastin
fiber deficient (sagging) skin laying over the moving
muscles of your face. It is important to use Ethocyn in
order to increase elastin fiber content and quality in your
skin if you are 25 years of age or over. This is true for
both men and women, of every ethnicity. Use Ethocyn
twice a day, every day, to assure optimum skin elastin
fiber content and obtain smooth, firm, and resilient skin
that snaps back.
Dermis
Reticular Dermis
Papillary Dermis
Subcutaneous
Tissue
Capillary
Elastin
ELASTIN
Series II: Active Isomer Composition of Matter patents; Process
patents and Use patents. Issued and pending
O
Trademarks: Ethocyn; ChanTal; Ethocyn by chanTal; Procol; Logo (2)
MWT: 266.4
C17H30O2
SYNOPSIS:
Ethocyn, 6-(5-ethoxyhept-1-yl) bicyclo [3.3.0] ocatan-3-one, is safe and efficacious target tissue, non-steroidal compound which
competitively inhibits dihydrotestosterone (DHT) receptor binding in fibroblasts derived from cutaneous tissue. Pharmacological
studies confirm that Ethocyn, after topical application, is rapidly (8-10 hours) in the skin to an inactive metabolite. There is no
Ethocyn absorbed into plasma. Toxicological studies (44 studies; 5 species) demonstrated Ethocyn to be non-toxic in doses up to
2,500; this is the clinically efficacious dose of Ethocyn Essence by chanTal serums.
Collagen
One Product.
Two Biopsies.
(One to know you need it.
One to know it works.)
Fibroblast cell
HOOC
Science strives for certainty.
Ethocyn delivers it (p<0.001).
FOR INFORMATION REGARDING
THE BCS PHARMA PHYSICIAN DISTRIBUTOR PROGRAM
PLEASE CONTACT US AT:
NH2
CH
H2N
CH
(CH2)2
(CH2)3
COOH
(CH2)2
CH
NH2
HOOC
N
mdinfo@ethocyn.com
www.ethoycn.com
“It is medically proven (p<0.001) that Ethocyn gives you
the important skin elastin content of 20 year old skin.”
(CH2)4
CH
H2N
COOH
Copyright 2012 BCS Pharma Pte. Ltd.
All Rights Reserved.
Made in the USA
- Jeffrey Hoefflin, M.D., FACS
Diplomate, The American Board of Plastic Surgery
Fellow, The American College of Surgeons
ETHOCYN RESEARCH AND DEVELOPMENT
ETHOCYN RESEARCH AND DEVELOPMENT
ETHOCYN RESEARCH AND DEVELOPMENT
Ethocyn Clinical Trials (contd):
Ethocyn Clinical Trials:
Ethocyn Pre-Clinical Studies
EFFICACY:
EFFICACY:
EFFICACY:
- Ethocyn Clinical Trial Dose Response Study: Clinical Investigator: Jeffrey Hoefflin M.D. FACS; Study Duration: 2 Months; N=32;
(28 females; 4 males) in Ethocyn Essence Serum by chanTal; Ethocyn applied topically b.i.d. (2x/day) regimen; Dose - 0.25% Ethocyn
and 0.025% Ethocyn in Ethocyn Essence Serum vehicle; 2mm biopsies ventral forearm; Biopsies taken at baseline, 1 and 2 months.
Biopsy analysis: As per prior Ethocyn Trials analyses.
- UCLA Univ Medical Center Pilot Ethocyn Clinical Trial I: Clinical Investigator - Dr. Richard Strick, M.D., Prof Dermatology UCLA;
Study Duration 6 Months; N=20 Subjects/Participants (17 females,3 males); Ages 40-57 yrs; Ethocyn applied topically b.i.d. (2x/day)
regimen; Dose-5.0% Ethocyn in alcohol and water vehicle; 2mm biopsies ventral forearm; Biopsies taken at baseline, 2, 4, and 6 months.
Biopsy analysis: slides were randomized thus hiding identity of the Subject and time sequence; Verhoeff’s elastin tissue stain; Computer
Image Analysis was performed to determine the percentages of surface area of each slide that took up the elastic tissue stain. All were
analyzed blindly.
- UCLA Univ Medical Center Ethocyn Clinical Trial II: Same Center and Clinical Investigator: Dr. Richard Strick M.D.; Study Duration3 Months; N=47 Subjects of which 29 Subjects (21 females; 8 males); Aged 40-77yrs and a Control Group (N=18 subjects Aged 18-25
yrs; 8 females; 10 males); Ethocyn applied topically b.i.d. (2x/day) regimen; Dose - 0.5% Ethocyn in Ethocyn Essence Serum by chanTal
serum vehicle; 2mm biopsies ventral forearm; Biopsies taken at baseline, 1, 2 and 3 months. Biopsy analysis: slides were randomized
thus hiding identity of the patient and time sequence; Verhoeff’s elastin tissue stain; computer image analysis was performed to determine
the percentages of surface area of each slide that took up the elastic tissue stain. All were analyzed blindly.
- DHT Receptor Lab Assays (Kd and AA activity confirmed) UCLA; CLMG: Univ Florida
- SEM skin biopsy (early Physician IND pilot clinical trial) confirmed Ethocyn made skin texture smoother more elastic
- Hamster Flank AA animal model: confirmed in animal model is a local, non systemic AA
- In Vitro Androgen Receptor Functional Assay- a gene expression system assay w/ Luciferase expression
- A gene expression system assay w/ Luciferase expression
- Genes Expression DNA Micro Assay - confirmation of Ethocyn’s up-regulation of the elastin synthesis gene(s); and Ethocyn's
down-regulation of mmp production gene(s).
SYNOPSIS:
This Clinical Trial Results confirmed what earlier Ethocyn Trials concluded that Ethocyn increases Subjects’ elastin fiber content to that
of 20 year old skin elastin fiber content after twice a day topical application for 60 days. At 30 days, the elastin content of all patients
was 50%(mean) of that realized in 60 days. (p=0.02)
RESULTS:
- Both formulations( 0. 25%and 0.025% Ethocyn)showed a statistically significant increase in elastin content.
- The 60 day treatment data for both dose groups were statistically identical to referenced (18-25 year old Subjects % elastin as reported
by Dr. Richard Strick, UCLA Clinical Investigator) Control Group data.
- The 60 day treatment data for both groups were statistically identical to each other.
SAFETY:
- UCLA and Shanghai Clinical Trials Protocols’ Participants Laboratory Evaluations:
Hematology: White Blood Cells, Hemoglobin, Blood Platelet Count, Red Blood Cells;
Urinalysis: White Blood Cells, Red Blood Cells, Protein, Others;
Serum Chemistry: SGPT, SGOT, Total Protein, Cholesterol, Creatinine, Potassium, Sodium, BUN, Alkaline Phosphatase, Triglycerides,
Total Bilirubin;
Hormone Assay: Total and Free Testosterone (TT and FT), Leutinizing Stimulating Hormone (LH), Follicle Stimulating Hormone (FSH),
Estradiol.
SYNOPSIS AND CONCLUSION:
For all Subjects in all Ethocyn Clinical Trial Studies: All laboratory results both in baseline and final visit were normal. During the analysis
14
of the lab records, no significant change between before treatment and after treatment was found. This was in line with the Ethocyn C
Clinical Trial that confirmed its 100% metabolism by beta oxidation such that there is no parent Ethocyn compound entering systemic
circulation.
No other skin care product in the
world can do what Ethocyn does ...
“The single most important cause of age related wrinkles
is the loss of skin elastin fibers. Elastin fibers are the
restorative force on the skin. Everyone, whether male or
female, will begin to lose skin elastin fibers at age 25. Only
one product in the world can restore your elastin levels to
that of 20 year old skin: Ethocyn.”
- Peter T. Pugliese, M.D.
Author of the medically acclaimed “Skin Physiology II”
and “Advanced Professional Skin Care”
SYNOPSIS:
Tables available at Ethocyn website: www.ethocyn.com; The Clinical Investigator presented his findings regarding both Clinical Trials at
the American Academy of Dermatology Conference where he reported that Ethocyn, after 60 day (b.i.d. - twice per day application) topical
use, by males and females, there was quantitatively observed over a 100% (mean) increase of skin elastin fiber content (p<0.001) in over
80% of the clinical trial participants of the first Pilot Clinical Trial and all participants in his Second 3 Month Clinical Trial. The elastin
content of the older (40-77 years of age) population was equal in elastin fiber content to that of “young skin” Control Group (aged: 18-25
years). The two percent (i.e. 2 patients) of the clinical trial participants in the Pilot Study that showed no increase in skin elastin fiber
content after use of Ethocyn were genetically gifted in that their skin contained a pre-Ethocyn treatment high elastin fiber content.
RESULTS:
- The first month elastic tissue results showed a greater than 50% increase
- At two months the increase was over 100% with all Subjects showing a response (Second Study)
- The Subjects’ skin had become visibly less wrinkled, especially when they smiled, frowned or talked. In many cases, the skin improved
dramatically.
- By the end of three months, there was an even further increase in the average elastic tissue levels.
- By two months, the elastic tissue levels were comparable to the levels found in the Control Group of 18-25 year olds (average age 20).
- Upon microscopic examination the quality of the elastin that had been produced was that of the normal elastin seen in youth.
- Subjects reported that that their skin was “smoother, tighter and less wrinkled.”
- The evaluation of ultra close up photographs from the beginning to the end of the Studies confirmed that the use of Ethocyn improved
the appearance at a high level of statistical significance.
- Independent statistical analysis of each of these trials concluded p<0.001
- Clinical Investigator conclusion in his medial conferences and journal publications: “Ethocyn is medically proven (p<0.001) to give you
the important skin elastin fiber content of 20 year old skin.”
- University Of Shanghai, Shanghai Institute of Dermatology Ethocyn Dose Response Clinical Trial: Clinical Investigators: Dr. Xue
Ming Wang M.D.,Zin Ying Zhou, M.D., Yi Hong Jiang Medical Doctor, Yin Fen Lin-Medical Doctor; N=158 divided into 4 groups: 20-29 yrs;
30-39 yrs; 40-49 yrs; 50-60 yrs; (106 females, 52 males); Study Duration - 60 days for 20-39 yr old subjects; 120 days for 40-60 yr old
Subjects; Asian skin only Subjects; Doses: Ethocyn applied topically b.i.d. (2x/day) regimen; Doses: 5.0%, 0.5%, 0.25% in alcohol and
water vehicle; 2mm biopsies ventral forearm; biopsies taken at baseline, mid-study and end of Trial. Biopsy analysis: As per prior UCLA
Clinical Trials analyses.
SYNOPSIS:
This Shanghai Ethocyn Clinical Trial on Asian Subjects/Participants showed the same profiles of baseline elastin content over different
age populations, male and females as Caucasian and Hispanic Subjects who participated in the UCLA Clinical Trials. Computer image
analysis of the elastin stained tissue slides after b.i.d Ethocyn topical application showed a significant increase in elastin, analogous to
the increases observed in the prior two UCLA studies. The average increase in skin elastin fiber content over the entire Shanghai Ethocyn
Clinical Trial was 88% (p<0.01) for ages 20-60 years of age. The average increase in elastin content for Subjects in the 40-60 age Group
was 96%, analogous to the UCLA mean 100% increase over the same aged (40-77 yrs) population.
RESULTS:
- Ethocyn Clinical Trial Results (p<0.001) was confirmed to be the same for Asian as were the clinical trial results in Caucasian and
Hispanic skin
- There were no significant differences in the efficacy of Ethocyn dosages amongst the Shanghai Clinical Trial doses of 5.0%, - 0.5% and
0.25%.
- Ethocyn is medically proven (p<0.001) to give Asian Subjects (aged 20-60 years of age) the important skin elastin fiber content of 20
year old skin.”
SYNOPSIS:
Ethocyn in H3 receptor assays confirmed its ability to competitively block intracellular DHT from binding to the DHT receptor. Ethocyn
Kd’s were established as the first proof of this novel chemical structure to be a non steroidal anti androgen. Early, Ethocyn pre IND
clinical trials established its mechanism of action to be a DHT receptor specific anti androgen which is specific to the site of topical
application (hamster flank assay). Speculation at this early stage of testing was that the Ethocyn molecule must be undergoing rapid
skin metabolism to a non-AA metabolite. This was later confirmed in C14 clinical trials in Groningen, Holland. In recent years, advances
in gene modulation technology has further validated Ethocyn’s mechanism of action to be a DHT specific non steroidal anti androgen.
Ethocyn exhibits no affinity for either the progesterone or estrogen receptor. It is very specific in its mechanism of action, a desired
characteristic to minimize chances of any side effects.
SAFETY:
- 44 safety studies; 5 species
- H 3,C14, HPLC extensive quantitative analysis at independent laboratories recommended by FDA, IKS, BGA
- Vehicle formulation pre-clinical trials
- Dose comparisons pre-clinical trials
- IND approval after 7 years, USD $18million in preclinical studies
SYNOPSIS:
Ethocyn pre-clinical studies were designed to evaluate the safety and toxicity of Ethocyn and its metabolite(s) when administered
topically, by ocular installation or orally to laboratory animals under varied experimental conditions. The pre-clinical program
encompassed evaluation of mutagenicity with Ames Assay, acute toxicity following oral administration to rats, primary dermal irritation
in rabbit, primary ocular irritation in rabbit, subchronic toxicity following dermal application in rat, photoallergic response and contact
sensitization (Magnusson/Kligman) following dermal application in guinea pig, teratogenicity studies in rat. Absorption, tissue
distribution and excretion profiles of Ethocyn were determined in rats after dermal application of radiolabeled Ethocyn.
RESULTS:
- Ethocyn is without mutagenic activity in the standard Ames Assay.
- The Ethocyn compound is non toxic in fourteen day acute oral toxicity tests, non-irritating when administered dermally and
non-irritating to ocular tissue as determined in animal studies.
- Ethocyn produced no systemic toxic effect when applied dermally for 90-days (2.5, 25 mg/kg in rats (60x a 1% clinical dose in human
skin; the clinical dose confirming clinical efficacy is 0.025%).
- The compound did not induce photosensitivity, contact irritant or photoallergic response or contact sensitization in guinea pigs after
dermal application.
- Ethocyn was not embryo toxic or teratogenic in rat teratology studies when applied dermally.
- Ethocyn was metabolized to a non anti androgen metabolite when applied dermally.
- Percutaneous absorption of Ethocyn characterized in an in vitro diffusion model studies system with animal skins indicate that the flux
(%dose/hr/cm2) rate of absorption of the applied dose was greatest in rabbit skin followed by rat-monkey-human-pig. HPLC analysis
shows that Ethocyn is metabolized in the skin to a group of metabolites including a less polar metabolite, none of the metabolites
having anti androgen activity.
- Such preclinical investigation and conclusions resulted in an IND issuance by USA FDA permitting Ethocyn to move into human
clinical trials, anticipating no side effects.