Nuliv An Overview Of Nu Liv Science 2010 6 21

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Presenting NuLiv Science International July, 2010

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NuLivScience Profile

Transcript of Nuliv An Overview Of Nu Liv Science 2010 6 21

Page 1: Nuliv An Overview Of Nu Liv Science 2010 6 21

Presenting

NuLiv Science International

July, 2010

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NuLiv Operates on 6 Interconnected Business Platforms

1. Focused RESEARCH on METABOLISM (slides 3- 16)2. Discovery of novel, safe, and BIOACTIVE botanical FRACTIONS & COMPOUNDS (slides 17 - 25)3. Development of PRODUCTION PROCESS for NuLiv’s proprietary

bioactive fractions and compounds (slides 26 – 28)4. Development of safe and effective SUPPLEMENT products (slides

29)5. SOURCING and QC of botanical ingredients (slides 30 – 31)6. Futuristic WELLNESS products and services platform (A NuLiv

experimental model) (slides 32)

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Focused Research on Metabolism

For close to a decade, NuLiv has centered its research around metabolism, the biological functions that sustain life, at cellularand systemic levels

1. Research initiatives (slides 4 – 6) 1.1 Central belief 1.2 Hypothesis 1.3 Strategy2. Life Science and Clinical Research platforms (slides 7 –14) 2.1 Facility 2.2 Staff & advisors 2.3 Validation platform 2.4 Supporting framework3. Patents (slide 15)4. Papers (slide 16)

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The Central Belief that laid down the Foundation for Our Research

TCM offers the best organized and time tested holistic and systemic health wisdom.

NuLiv’s research idea, discovery of novel bioactiveingredients, and development of nutritional products

should germinate from this knowledge base

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The Hypothesis Our Research Strategy is Built Upon

• “Qi” (breathing, life force, energy) and “Xue” (circulation), the foundation of TCM principle, are the metaphysical

transformation and final manifestation and distribution of nutrients in human body.

• The biological pathway of this manifestation and distribution, i.e., nutrient absorption, transportation of nutrients through bodily fluids (blood included), metabolic and catabolic functions, regulation of haemopoiesis & angiogenic functions, even its effect on immune functions, are all integral to this final manifestation.

• “Qi” and “Xue” herbs must be bioactively involved in the various biological pathways and functions. Study of these herbs should offer better odds of novel discoveries and understanding of their benefits toward human health.

.

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Our Strategy is to Build a Research Platform that Allow us to Discover Novel Bioactive Compounds

from Chinese “Qi” and “Xue” Herbs

1. Select safe and widely used TCM herbs as research subjects.2. Extract, separate, fractionate, and purify these herbs to fraction and/or compound levels.3. Develop bioassays to identify purity and concentration level of

these fractions and compounds.4. Formulate application specific functional ingredients composed

of these fractions and/or compounds and assay for their efficacies.

5. Test ingredient efficacy and safety to the technical or financial level that is feasible; cell, animal and human.

6. Develop and test for ingredient reproducibility and stability.

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NuLiv’s Advanced and Integrated Life Science and Clinical Research Platform

Component DescriptionFacility NuLiv Taipei Laboratory

NuLiv Shanghai Laboratory

Management, Staff and Advisors

Highly educated and trained in business, multi scientific & clinical disciplines, and work closely in a truly interdisciplinary manner

Discovery and Validation In-house and 3rd party in vitro, in vivo, and human use study platforms

Supporting Framework/Network

Supported by NuLiv’s own subsidiaries and affiliates, and long term strategic partners and alliances in many distinguished academic and research institutions

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Research FacilitiesTaipei and Shanghai Laboratories

• NuLiv Taipei (NDMC) Laboratory

1. Research initiatives 2. Research: Chemistry, cell assay, animal and human study on plant derived bioactive fractions/compounds 3. Product design and development 4. Production process development

• NuLiv Shanghai Laboratory

1. Extraction, fractionation, purification of botanicals 2. Production process, MOA, and CMC development 3. Sourcing and Procurement 4. QA and QC

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Laminar

Flow, Cell

Culture

Water

Purification

System

CO2

IncubatorLab Bench

Spectrophotometer

Photomicrographic

Equipment

High Speed

Centrifuge

PCR machine

Gel Dryer Deep Fryer

Gel Photosystem

Animal Room

National Defense Medical Center

NuLiv Taipei Laboratory Has Access to Equipmentsto Perform a Wide Range of In Vitro and In Vivo Studies

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Shanghai laboratory Develops Production Process Criteria, Performs QC

Extraction/Separation /Isolation Room

Chemical Analysis Room Extraction Equipments

Waters 2695 HPLC Agilent 1100 HPLCAgilent

6890N/5973

GC/MS

Camag TLCS

Shimadzu 2401PC UV

spectrophotometer

Nikon YS2

biological

microscope

Instrumental Analysis Room

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NuLiv Management /Business & Research Executives

Founder & CEO Austin Wang, M.S. NuLiv Holdings, Inc. (World Headquarters) Taipei City, Taiwan

Executive DirectorY.H. Lee, M.D. Vice Chancellor, China Medical Univ. (Taiwan), Previously Dean, Chang Kung Medical School, Dep. Director, Chang Kung Hospital System (10,000+ beds)

Principle Scientific Advisor H.C. Lin, Ph.D. Univ. of North Carolina. Taught TCM at NDMC for over 20 years. Pioneered the hypothesis that “Qi” herbs regulate absorption and other metabolic functions

PresidentAmericas, Europe, Asia, Africa

Business DevelopmentSales & Marketing Representative

Americas, Europe, Asia, Africa

Michael Wang, M.S. NuLiv Science USA, Walnut, CA

David Allen, Ph.D. World Wellness, LLC., San Diego, CA

PresidentGreater China

David Wu, Ph.D. Business Administration, Univ. of South Australia,

DirectorResearch & Development

NuLiv Taipei Laboratory

Thomas Yang, Ph.D., Molecular Microbiology, Univ. of Texas, Southwestern Medical Center

DirectorNuLiv Shanghai Laboratory

Sunnie Sun, Ph.D., Pharm. Analysis, Sheng Yang Pharm. Univ.

DirectorClinical Research

Rose Chen, M.D., Ph.D., Shanghai TCM University

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NuLiv’s Scientific Advisors

Chang, T.C., Ph.D. Biochemistry, Univ. of Illinois, Professor, Dept. of Biochemistry, National Defense Medical Center,Taiwan

Chang, W.L., Ph.D. Pharmacy, National Taiwan Univ., Professor, School. of Pharmacy, National Defense Medical Center, Taiwan

Kuo, C.H., Ph.D. Physiokinetics, Univ. of Texas, Professor and Chair, Department of Exercise Science, National Taipei Physical Education College, Taiwan

Chen, C.X., Professor Director, Department of Pharmacology, TCM Univ., Shanghai, China. Serves as our toxicity and safety advisor on TCM and other herbs

Komatsu, Yasuhiro, Ph.D.

Medical science, Juntendo University, Prior Dean of R&D department, Tsumura & Co.

Chu, C. H, Ph.D. Food engineering, University of Tokyo, expert in pre-clinical pharmacology tests

Fan, David, Ph.D. Senior Lecturer, Trinity College, Cambridge Univ., Editor-in-chief, Angiogenesis

Hsieh, Steve, Ph.D. Nutritional Biochemistry, Univ. of Wisconsin, Ex Vice Chairman, National Science Council, R.O.C. Government

Looi Hwang, Ph.D. Industrial & Environmental Pharmacy Ph.D. from Purdue, previously G.M. of MSD, Hanzhou, China & and Merck of Singapore

J.K. Luo, Ph.D. Editor (acting), Journal of Heterocyclic Chemistry, Professor at University of S. Florida

Funfack, Wolf, M.D. Metabolic Balance founder.

Peng, C.K., Ph.D. Statistical Physics, Boston Univ., Assoc. Professor/Co-director, Rey Institute for Nonlinear Dynamics in Physiology and Medicine, Harvard Medical School.

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Our In vitro, In vivo, and Human Research Platforms

In vitro Assay Systems

• Establish any cell assay system in 2 to 4 months• Currently available cell assay systems: HaCaT and HDF cell, Caco-2, 3T3-L1, HSMMT,HepG2, HCH & SW 1353, and etc

In vivo Assay for efficacy and

safety Systems

• Nude mice for cancer and cosmetic studies• db/db mice for diabetes and wound healing studies• SD rat for ergogenic and diabetes studies• absorption model (portal vein)• Acute and Sub-acute Toxicity

Human use Study

• Topical skin care test• Ergogenic test • Cancer adjuvant therapy

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Our Supporting Framework & Network

Facility, equipment, interdisciplinary consultation

National Defense Medical CenterIndustrial Technology Research institute, TaiwanYang Ming University, TaiwanTaipei Medical University, Taiwan

In vivo and human study China Pharmaceutical University, Nanjing, China Taipei Physical Education CollegeI-Shou University HospitalNuLiv Wellness Clinic

Consultation, Cellular science Metabolic health TCM pharmacology & toxicology angiogenesis

Yang Ming Univ. Stem Cell Research CenterTaipei Medical Univ. Stem Cell Research CenterDr. Wolfgang Funfack, Metabolic Balance, De. Shanghai TCM universityChina Medical University, TaiwanTrinity college, Cambridge University, UK

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Title Country/Region Patent NO. Application NO.

Method for Regulating Nutrient Absorption with Astragalosides

USA US11/426,029

China CN200610090113.0

Taiwan I271195

Method for Regulating Nutrient Absorption with Ginsenosides

USA US11/426,06

ChinaCN200610090114.5 CN200910178493.7CN200910178492.2

Taiwan I317280 Method for Skin Care PCT PCT/US07/77326

USA US11/469,659

China CN200710089586.3

Taiwan TW095132614

Use of Cycloartane compounds for treating arthritis

USA US12/353,779

China N/A yet

Taiwan TW098135306

Patents from NuLiv’s Research

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• Effect of ginsenosides on glucose uptake in human Caco-2 cells is mediated through altered Na+/glucose cotransporter 1 expression. Chang TC, Huang SF, Yang TC, Chan FN, Lin HC, Chang WL. J Agric Food Chem. 2007 ;55(5):1993-8.

• Effect and mechanism of ginsenosides CK and Rg1 on stimulation of glucose uptake in 3T3-L1 adipocytes. Huang YC, Lin CY, Huang SF, Lin HC, Chang WL, Chang TC. J Agric Food Chem. 2010 ;58(10):6039-47.

• Glycogen overload by postexercise insulin administration abolished the exercise-induced increase in GLUT4 protein. Chou CH, Tsai YL, Hou CW, Lee HH, Chang WH, Lin TW, Hsu TH, Huang YJ, Kuo CH. J Biomed Sci. 2005 ;12(6):991-8.

• The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma cell therapy. Chen YL, Jian MH, Lin CC, Kang JC, Chen SP, Lin PC, Hung PJ, Chen JR, Chang WL, Lin SZ, Harn HJ.Mol Pharmacol. 2008 ;74(4):1046-58.

• The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. Tsai NM, Chen YL, Lee CC, Lin PC, Cheng YL, Chang WL, Lin SZ, Harn HJ. J Neurochem. 2006;99(4):1251-62.

• The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo. Tsai NM, Lin SZ, Lee CC, Chen SP, Su HC, Chang WL, Harn HJ. Clin Cancer Res. 2005;11(9):3475-84.

• Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. Cheng YL, Chang WL, Lee SC, Liu YG, Chen CJ, Lin SZ, Tsai NM, Yu DS, Yen CY, Harn HJ. Life Sci. 2004;75(13):1579-94.

• Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor through the oestrogen beta receptor.

• Leung KW, Cheung LW, Pon YL, Wong RN, Mak NK, Fan TP, Au SC, Tombran-Tink J, Wong AS. Br J Pharmacol. 2007;152(2):207-15. • Metabolites of ginsenosides as novel BCRP inhibitors. Jin J, Shahi S, Kang HK, van Veen HW, Fan TP. Biochem Biophys Res

Commun. 2006;345(4):1308-14.• Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. Leung KW, Cheng YK, Mak NK, Chan

KK, Fan TP, Wong RN.FEBS Lett. 2006 ;580(13):3211-6 • Modulating angiogenesis: the yin and the yang in ginseng. Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW,

Yeung HW, Wong RN, Sasisekharan R, Fan TP. Circulation. 2004;110(10):1219-25. • S.-F. Huang, Y.-C. Huang, J.-Y. Lin, W.-L. Chang and T.-C. Chang (2010) Effect of Ginsenoside Rb1 on Glucose Uptake and Expression

of Glucose Transporters in Animal Cells, Adaptation Biology and Medicine, Volume 6: Cell Adaptations and Challenges, 2010 (In Press).

• Yu-Chuan Huang, Cheng-Yu Lin, Su-Fen Huang, Wen-Liang Chang, and Tsu-Chung Chang (2010) Differential effect of oleanolic and ursolic acid on GLUT4 expression and membrane translocation in 3T3-L1 adipocytes, Manuscript in preparation .

Published Papers and papers in Press

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Discovery of Novel, Safe, and Bioactive Botanical Fractions and Compounds

After a decade of following our research central belief, hypothesis, and strategy,and by subjecting dozen “Qi” and “Xue” herbs through our in vitro, in vivo, andhuman studies, we have discovered 6 bioactive fractions and compounds inthese herbs that have shown dose-dependent benefit toward specific humanfunctions

1. 6 bioactive fractions / compounds discovered (slide 18)2. Functional ingredients formulated with our bioactive fractions/compounds

2.1 Brief descriptions of the 6 functional ingredients (slide 19)2.2 ActiGinTM, for optimum exercise energy, endurance, and recovery (slide 20)2.3 AstraGinTM, for enhanced nutrients absorption at the cellular level (slide 21)2,4 AstrionTM, for youthful and radiant skin (slide 22) 2.5 ImmunoAGTM, for adjuvant therapy (slide 23)2.6 OsteoSineTM, for reversing bone loss (slide 24)2.7 Slim&FitTM, for weight control and metabolic syndrome (slide 25)

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6 Fractions / Compounds from our Research and Their Biological Functions

Fractions/Compounds Discovered

Functions

NL-F001 Anti-angiogeneisNL-F002 Enhance amino acids, vitamins, and

glucose absorption at the cellular level; anti-angiogenesis

NL-F003 Increase Adiponectin secretionErgogenic/recovery

NL-F004 Enhance amino acids, vitamins, and glucose absorption at the cellular level

NL-F006 Enhance amino acids, vitamins, and glucose absorption at the cellular level ; Increase Adiponectin secretion

NL-F007 Increase collagen and hyaluronic acid secretion; decrease MMP-1 secretion

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Proprietary Nutraceutical Ingredients Formulated with NuLiv Bioactive Fractions and Compounds

AstraGinTM An all natural nutrient uptake enhancing complex that improves amino acids, glucose, vitamins absorption by 62%, 57%, 50% through regulation and parallel alteration on both the protein and mRNA expression levels of the nutrient transporter genes

AstrionTM Reduces the number and appearance of fine lines & wrinkles, skin discoloration due to sun damage, and firms, tones, and hydrates skin through increased dermal genesis and UV protection. Dermal genesis promotes the synthesis of new collagen and hyaluronic acid and, at the same time, reduces the breakdown of existing collagen due to UV light destruction

ActiGinTM Increased delivery of glucose to muscle cells; Protect against free radical attack after exercise; Anti-inflammation; Minimize muscle cell damage; Increased glycogen replenishment after Intensive workout

ImmunoAGTM ImmunoAGTM promotes nutrient absorption and metabolism in intestinal cells, Inhibits abnormal cell proliferation and angiogenesis, induces abnormal cell mitotic arrest and apoptosis through the activation of multiple signal pathways. In an in vivo study, ImmunoAGTM demonstrated to inhibit abnormal cell growth by 44% and prolonged the life of subcutaneous abnormal cell bearing rats by 33% when compared to a control group.

OsteoSineTM Promotes bone mineral density and structural strength by enhancing bone formation and reducing bone resorption. This dual action has been confirmed by NuLiv’s PO (post-ovariectomized) female rats (equivalent to menopausal women) and RA (retinoic Acid-induced acute osteoporosis) rats (Equivalent to none gender or age-related osteoporosis persons) models.

Slim&FitTM Decreases the intestinal absorption of glucose through the regulation and parallel alteration on both the protein and mRNA expression levels of the nutrient transporter genes while increases the glucose absorption in muscle and adipocyte cells through insulin independent pathway.

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Creatine kinase

MDAIL-6 Inflammatory

biomarkers inhibition

Exercise

Oxidative stresselevation

Glucose uptake

Oxidative stressreduction

ATP

How ActiGinTM Works

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How AstraGinTM Works

AstraGinTM’s Nutrients Absorption Model

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How AstrionTM Works

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Pharmacodynamics of ImmunoAGTM

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OsteoSineTM In vivo Study

Normal bone treated with retinoic

acid to simulate osteoporosis

conditions

Treated with 400 mg of

OsteoSine daily for 5 weeks

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How Slim&FitTM Works

Slim&Fit TM’s Biological Pathways/Mechanisms on Regulating Metabolic Functions

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Development of Production Process for

NuLiv’s Proprietary Bioactive Fractions and Compounds

We develop production process, reference standard, MOA,bioassay, and QA Programs for the production of ourproprietary active fractions and compounds so that theyhave the same purity and concentration level as in thoseused in our research.

1. Extraction, Fractionation, Separation, and Purification of Raw Herbs to the Fraction and Compound Levels (slide 27)

2. Purity and concentration level of our proprietary bioactive fractions / compounds are identified and measured by specific bioassays (slide 28)

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Extraction, Fractionation, Separation, and Purification of Raw Herbs to Fraction and Compound Levels

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The Purity and Concentration Level of our Bioactive Fractionsand Compounds are Identified and Measured by Specific Bioassays

Active constituentsMedicinal plants

Crude extracts

Fraction 1Fraction 2Fraction 3Fraction 4Fraction 5Fraction 6…

fractionationextraction

FormulationDepend on function

Products & Marketing

Structure elucidation

UVMSNMRIRCD

1H NMR13C NMR2D NMR

separation

Absorption

Anti-cancer

Skin care, etc

Active constituents

QC systems-LC/UV-GC/MS

Bioassay

QC

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Our Supplements are Highly Effective and Safein Supporting Critical Human Health Functions

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Our Sourcing Operations Guarantees Premier Quality Products with Competitive Prices and Timely Delivery to our Customers

NuLiv/Customer specifications/requirements

Vendor

Vendor Survey for Certificates, Qualifications, MOA, COA, sample

Onsite Vendor Survey

DisqualifiedQualified

Contract/Agreement

Primary

suppliers

SecondarySupplier

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Our Quality Control on Sourcing OperationsClosely Follows Pharmaceutical Protocols

• Follow USP/NF, AOAC, ChP, GB, In-house developed MOA• PhytoMonitorTM Double QC Checking

– First tested at the manufacturing sites or production sample tested at NuLiv shanghai Laboratory

– Production order samples tested at NuLiv Shanghai laboratory before order can be shipped.

– Samples can be tested by independent 3rd party laboratories in the U.S. for additional quality control.

– Alkemists Pharmaceuticals, CA– Michelson Lab, CA– Oregon Department of Agriculture (heavy metals)

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Futuristic Wellness Product and Service Platform(A NuLiv Experimental Model)

Wellness Advisors

Interactive and personalwellness information exchange

and virtual community managementNuLiv Wellness Management Inc.

DeviceHRM Meridian

Blood analysis CD/Biochips

Nutritional SciencesNuLiv Laboratories

(Slides 1 – 42)System complexity analysisDynaDx – Harvard Reylab

Evidence based wellness know-how

NuLiv Wellness Clinic

Wellness/Sub-clinical Primary Care Clinic

Cellular sciencesSteminent Therapeutic Inc.

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Whether its research capability,cutting edge proprietary botanical fractions,

highly effective nutritional supplement products, premium quality botanical ingredients,

or even Futuristic Wellness Model, NuLiv Science is the company that you can trust.

Thank you