Nuliv An Overview Of Nu Liv Science 2010 6 21
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Transcript of Nuliv An Overview Of Nu Liv Science 2010 6 21
Presenting
NuLiv Science International
July, 2010
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)
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)
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
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.
.
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.
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
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
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
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
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
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.
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
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
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
• 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
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)
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
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.
Creatine kinase
MDAIL-6 Inflammatory
biomarkers inhibition
Exercise
Oxidative stresselevation
Glucose uptake
Oxidative stressreduction
ATP
How ActiGinTM Works
How AstraGinTM Works
AstraGinTM’s Nutrients Absorption Model
How AstrionTM Works
Pharmacodynamics of ImmunoAGTM
OsteoSineTM In vivo Study
Normal bone treated with retinoic
acid to simulate osteoporosis
conditions
Treated with 400 mg of
OsteoSine daily for 5 weeks
How Slim&FitTM Works
Slim&Fit TM’s Biological Pathways/Mechanisms on Regulating Metabolic Functions
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)
Extraction, Fractionation, Separation, and Purification of Raw Herbs to Fraction and Compound Levels
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
Our Supplements are Highly Effective and Safein Supporting Critical Human Health Functions
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
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)
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.
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