CBD with Preclinical Tests, under FDA guidelines to assist in the transfer to FDA regulation. Focusing on Bio-Availability, stability and Arthritis studies.
*This Information has not been evaluated by the FDA, the efficacy of these products are not intended to diagnose, treat, cure, or prevent any disease.
2. Research & Development
Hebrew University of Jerusalem, Israel
Center for Human Toxicology, College of
Pharmacy, University of Utah, USA
Pain Research Center, School of Medicine,
University of Utah, USA
Lyotropic Delivery Systems, Israel
PreClinical Research Services, Colorado, USA
Science in Action, Israel
• Tel Aviv University
• Technion
• Ben Gurion University
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3. Cannabidiol (CBD) Has the Potential
to Significantly Change Medicine and
Prophylactic (Wellness) Care
CBD – A non-psychoactive
molecule in industrial hemp
n industrial hemp
• A potent anti-inflammatory with
the exceptional ability to treat
many problematic, even life-
threatening health conditions
• Works by turning several
processes in the body on or off
4. • A non-psychoactive substance only found in
cannabis plants
▫ Particularly abundant in industrial hemp
• Published scientific studies indicate desirable
anti-inflammatory properties and a potential to
positively impact adverse and even life-
threatening conditions
▫ Cancer, diabetes, heart disease,
rheumatoid arthritis, epilepsy,
osteoarthritis,
inflammatory
bowel disease and more
▫ Neurodegenerative diseases such as multiple
sclerosis and Parkinson’s disease
▫ Protect the brain after concussion
▫ Trigger weight loss and lower blood sugar levels
Cannabidiol (CBD)
CBD Crystal
Purified from
Industrial Hemp
5. • Non-Psychoactive and Non-Addicting
• Does Not Induce Catalepsy
▫ No seizures involving sensation loss, muscular
rigidity, fixity of posture
• No Effects on Psychological or Motor Functions
▫ Movement, coordination, dexterity, strength,
speed
• No Impact on Basic Physiological Parameters
▫ Heart rate, blood pressure, body temperature
• No Changes in Food Intake or Gastrointestinal Transit
• Chronic Use and Larger Doses (> 1,500 mg/day) Well
Tolerated -- Lowered Blood Pressure at Higher Doses
• Inhibition of Hepatic Drug Metabolism (CYP 450)
• Decreased Activities of p-Glycoprotein and Other Drug
Transporters
CBD Crystal
Purified from
Industrial Hemp
Is CBD Safe for
Humans?
6. Value Proposition: A Groundbreaking
Public-Health Paradigm Shift
• Profound medicinal potential for safe,
non-addictive CBD
• Unmatched technology that greatly
boosts CBD’s therapeutic utility ―
innovation promoting better health the
saving of lives
• A cost-effective, compelling paradigm
shift centered on CBD for both
preventive healthcare and serious
medical interventions when applicable
Industrial Hemp
Flowering Stage
7. Regular CBD as a Human
Therapeutic Is a Problem
• Insoluble in Water
▫ Elevated solubility in water crucial for efficiently
getting from the mouth into the bloodstream
▫ Also, substantive aqueous solubility essential for
dissolving CBD in beverages
• Low Bioavailability
▫ Only minor amounts can reach the bloodstream
and thus to sites of action in the body
• Most CBD Is Wasted
▫ Either degrades in the stomach or otherwise
passed in feces
Problem Uniquely Resolved for the First Time
8. Entry of our CBD into the Body
Greatly Enhanced with One-of-a-Kind, Patented Technology1
Our methods have a molecular affinity with other.
• Vessel Size = 1/160,000
Width of a Human Hair
• Made with Safe, Edible
GRAS2 Substances
• CBD Uniquely and
Substantively Loaded
• Elevated Bioavailability
• Entry Into the Body
Greatly Amplified
• 100% Water Soluble
• Timed-Release Capable
• Low Bioavailability
• Barely Gets into the
Bloodstream when
Taken by Mouth
• Insoluble in Water
Our CBD
Liquid Structure CBDEmpty Vessel Regular CBD
CBD
CBD
1. A new generation of ultra-small, value-added structures that
spontaneously self-assemble into stable, functional vessels
2. GRAS = Generally Recognized as Safe, the USFDA designation for safe,
edible substances freely allowed in foods and beverages
High Solubility & Bioavailablity Uniquely
Achieved
+ =
9. Liposomes, Micelles & Liquid Structures
• Amphiphilic
• Low Target Load
• Unstable — Days
▫ pH Sensitive
▫ Altered by Proteins
• Refrigeration Necessary
Liquid
Structure
• 15-nm
Micelle
• 100-nm
• Amphiphilic
• Self Assembling
▫ Spontaneously Forms
Ultra-Small Constructs
• Large Target Load
• Highly Stable
• Long-Term Room
Temperature Storage
CBD
• Unstable — Hours
▫ Hydrolysis of Ester Bonds
▫ Peroxidation of Unsaturated
Acyl Chains.
▫ Aggregate and Leak
• Refrigeration Necessary
Liposome
• 200-nm
• Hydrophilic
• Very Low Target
Load
• Bacteriostatic
• Made Only With GRAS
Ingredients
10. • Extraordinarily Small, Stable CBD-Loaded
Receptacles, 15 nm Diameter, Specifically
Constructed for Maximizing the Entry of CBD
Into the Body
• Smaller than Unstable Liposomes (100- 150
nm) and Micelles (up to 200 nm)
Ineffectually Used by Others
• Human Hair – 160,000 nm Thick, Red
Blood Cell – 7,500 nm Diameter, Flu Virus
– 100 nm Diameter, HIV-1 Virus – 125 nm
Diameter, DNA Molecule – 2.5 nm Width
Liquid Structure CBD
Cryo-Electron Microscopy
Transmission Electron Microscopy at -200 oC (-330 oF)
CBD-Loaded
Receptacle
Empty
Receptacle
50 nm
50 nm
11. How Our Liquid Structure CBD is Efficiently
Brought from the Small Intestine to the
Bloodstream
• Liquid Structure CBD Attaches
to the Intestinal Wall
• Only CBD Passes Through
Membranes of the Intestinal
Wall & Into the Bloodstream
• The GRAS1 Liquid Structures
Do Not – Once Empty, Detach
from Intestinal Wall, Fall Apart
and Then Are Digested
• CBD’s Entry Into the Body is
Tremendously Increased
1GRAS = substances deemed safe in
foods by the USFDA
4
.
5 6
.
1 2 3
Intestinal Wall Bloodstream
..... .
EmptyUnit
Detaches
CBD-Loaded
Liquid Structure
Attaches to
Intestinal
Wall
CBD
Transferredto
Bloodstream
..
.
. . .
.......
. ..
.
.
• =CBD
EmptyUnit
Falls Apart
12. More Liquid Structure CBD
Gets Into the Body
Taken by Mouth
Amount in the Bloodstream (Plasma) at 30 Min.
Sprague Dawley
Rats
10 mg/kg
Dose
N = 10
in Each Group
Liquid Nano Droplet CBD
Regular CBD in Olive Oil
13. Taken by Mouth
Amount in the Bloodstream (Plasma) at 0.5 & 2.0 Hours
More Liquid Structure CBD Gets Into the Body
0.5 Hours 2.0 Hours
Liquid Structure CBD
Pure CBD in Olive
Oil
CBDinBlood
Plasma
ng/ml
Sprague Dawley
Rats
N = 10
In Each Group
25 mg/kg
Dose
14. Tumor Necrosis
Factor Alpha (TNF-α)
Our Liquid Structure CBD
& Inflammation
• A Key Inflammation-Causing Protein
▫ Made by immune-system cells
• An Underlying Factor in Many Diseases
▫ Rheumatoid arthritis, osteoarthritis, psoriatic
arthritis, ulcerative colitis, Crohn’s disease,
atherosclerosis, heart attack, diabetes
3D Model of
TNF-α Protein
15. TNF-α Levels Greatly Decreased with Liquid Structure CBD
• 50-mg Pure CBD in Olive Oil versus 5-mg Liquid Structure CBD
• 70% less TNF-α with 5-mg Liquid Structure CBD
CBD & Inflammation
Control Pure CBD in Olive Oil
N = 5 in Each Group
LiquidStructure
CBD
16. CBD May Transform to THC and More in the
Stomach
• Transformation to THC Means the Loss of CBD (Reduced
Bioavailability), Maybe Unwanted Psychoactive Effects and More
• Negative Ramifications for Drug Testing
• Resistance to Acid Hydrolysis a Necessity
17. CBD Transformation in
Gastrointestinal Fluid
• Liquid Structure CBD Reactive Site of the CBD Molecule
Protected, Thus Impervious to Chemical Change
• No CBD Transformation or Degradation
No CBD
Transformation
Unprotected CBD May Be
Altered in the Stomach, Thus
Wasted Prior to Reaching
Sites of Action
Liquid StructureCBD
Pure CBD in Olive Oil
• Almost All CBD Can Thus Reach the Small Intestine
18. Other CBD Formulations Convert in the Stomach
HPLC Spectra CBD and Degradation Products
0 Minutes 60 Minutes 120 Minutes
CBD in
Olive Oil
Popular
Commercial
CBD Oil Product
Our
Liquid Structure
CBD
• In Gastrointestinal Fluid, our CBD Does Not Transform to
Other Substances.
• CBD Altered in Other Preparations
19. LUMifuge™ Stability Analysis
• Breakthrough technology – Only tool worldwide for
accelerated and reliable, product stability testing
• Instabilities detected 2300X faster and more accurately
• Precise stability and shelf-life determinations in minutes
or hours, not months or years
• Product decay detected via changes in light transmission
HundredsofSensors
Light Source Sample Sensor Concentration
Stable –No Breakdown
Flocculation
Aggregation
Coalescence
Demulsification
Sedimentation
20. LUMIfuge Analysis & Our CBD
• No Breakdown
• Shelf Life 3 Years at
Room Temperature
• Live Active Testing
Diluted – 15% in Water
• No Breakdown Even
When Diluted
• Same Shelf Life as Full-
Strength our CBD
Sensors
Turning On
Sensors
Turning Off
Full Strength
22. Stable Across Temperatures
4 oC
39 oF
25 oC
77 oF
40 oC
10 oF
Day 0
Day 15
Day 30
Day 68
6
0
1
2
3
4
CBDConcentration(wt%)• Over a Time Span of 68 Days, No Obvious Degradation
of our CBD – Even at Higher Temperatures
6
5
23. Differential Scanning Calorimetry
Leo International
Liquid Structure CBD
Common
Empty Vessel
(Liquid Structure)
Conformational Stability of Liquid Structure CBD
Across a Broad Temperature Range
24. Bioavailability & Water Solubility
The ability of a substance to be dissolved in water -- a key
determinant of absorption into the bloodstream
Liquid CO2 (A)
Organic Solvent (B)
CBD Extracts
• Edible Oils Support
Bacterial Growth
Powdered CBD (A)
Liposomal CBD (B)
•Note Turbidity in B –
Liposomes Unstable, Fall
Apart and CBD Precipitates
• Supports Bacterial Growth
A B
Our Liquid
Structure CBD
2 Different
Formulas
• Bacteriostatic
Insoluble
Insoluble (A)
Partly Soluble (B)
Fully (100%)
Soluble in Water
A B
25. Liquid Structure CBD:
USFDA Clinical Trials in Israel
• Deemed Israel’s first
“cannabis” medicine by
the Ministry of Health
• Authorization for IRB
clinical trials for a major
medical condition
• USFDA approval for those
trials done in Israel – 1997
bi-lateral agreement
• Phase 1 – 2A in process
Sourasky Medical Center, Tel Aviv
26. Liquid Structure CBD’s Medicinal Potential
Safer Pain Management ― Resolving the Opioid Crisis? Case Study
The Opioid Epidemic Safe, Non-Addictive Liquid Structure CBD
Promising
Human Case Study Results• The most devastating drug crisis
in American history
• 175 deaths each day
• About 64,000 overdose deaths in
2017, one-half million since 2000
• Almost 1 million heroin users in
2016, more than 13,000 deaths
• Fentanyl ― 100 X stronger than
morphine, “number 1” reason
for opioid-related deaths
• Breakthrough pain ― frequent flares of
crippling pain, a huge problem in stage 4
cancer patients
• Fentanyl most often prescribed
• Case study (n = 40) ― non-addictive
nano-structure CBD taken 2X per day by
stage 4 cancer patients
• Fentanyl intake voluntarily decreased by
about 75%
• 25% of patients stopping fentanyl use
• Nano-shell CBD a seemingly effective
analgesic
27. How CBD Works ꟷ Receptors
Outside Cell
Cell Membrane
Inside Cell
CB1
Relaxation
Anxiolytic (Anti-Anxiety)
CBD DOES NOT BIND TO CB1 OR CB2
Indirectly upregulates the anandamide
(messenger molecule) made by the CB1
receptor (see above)
Enhances or inhibits the binding action of
certain G-protein coupled receptors.
THC
28. 10mg 30count White Label Bottle
5mg 60count White Label Bottle
• Naturally green due to phytonutrient's,
being reintroduced.
• Purest in form, highest
*All Softgels are Gluten and
lactose free.
Does not contain yeast,
dairy, eggs, wheat, corn,
sugar, starch, salt, artificial
flavors or fragrances