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Non-invasive Transdermal Delivery of

Medical Carbon Dioxide with D`OXYVA


Boosts Microcirculation, Balances
Parasympathetic/Sympathetic Nerve Activity

Delivers Wide Ranging


Industry-Leading Outcomes
Date: August 8, 2016

"There are a lot of possibilities here and we are really excited


about conducting future studies to determine what D`OXYVA
may be able to provide to people with microvascular disease.

- Prof. Judy M. Delp, Ph.D., Florida State University, U.S.A.

Think Beyond Different, Way Beyond Different

Transdermal Delivery Breakthrough


Concept: administration of active molecules to the body by DIRECT
TRANSMISSION THROUGH THE SKIN
Common: patches, microneedle, nanoparticles, high velocity fluid streams

Issues: DEVELOPMENT/USAGE IS 3X IN RECENT YEARS, but all try


penetrating skins MULTIPLE BARRIERS WITH SMALL MOLECULES
Benefits: GREAT ALTERNATIVE TO ORAL AND NEEDLE DELIVERY, greater
effectiveness, absorption with less invasiveness, patient discomfort

Solution: D`OXYVA OVERCOMES ALL ISSUES, ENHANCES DELIVERY


with proprietary, rapid, safe absorption process via skin pores; not
breaking skin barrier; enhancing absorption for small to large
molecules

D`OXYVA

Marketed exclusively by Circularity Healthcare

Oxygen Delivery Depends on:


1.
2.
3.
4.

Heart
Arteries
Arterioles
Capillaries

Decreased
resistance

Smooth
muscle
cell

Interior
of arteriole

Arteriole
Smooth muscle cells

Source: Prof. Judy M. Delp, PhD

Smooth
muscle
relaxation

Normal
resting
tone

Increased
resistance

Smooth
muscle
contraction

Importance of Microcirculation
Recognition of importance of proper microcirculatory
function is growing rapidly, improved microcirculatory health
can support better outcomes in a wide variety of conditions,
both localized and systemic
Optimal microvascular function is critical in regulating blood
flow, tissue perfusion, blood pressure, oxygen delivery, waste
removal
Proper functioning has beneficial effects on prevention,
treatment of disease states; sepsis8, non-healing wounds,
diabetes9, hypertension10, 11, obesity12, metabolic syndrome13,
respiratory disorders, sexual dysfunction, and age-related
syndromes

A Few Well-Known Benefits of Improved


Microvascular Function
D`OXYVA DELIVERS ALL AND MUCH MORE AT LEVELS NEVER
DETECTED BEFORE

Better, Faster
Healing

Increased
Metabolism
Pain Relief

Fatigue
Reduction

Better Sleep
Appetite

Targeting of Microcirculation
Studies suggest diabetics suffer most from macrovascular, microvascular
impairment, though there seems to be no limit

Traditional methods of revascularization surgery or angioplasty can repair the


macrovascular impairment, but no convincing studies showing microvascular
function improvements
Microvascular disease is implicated in foot ulcers and delayed healing
Expensive, inefficient therapies; HBOT (inconclusive studies), NPWT

D`OXYVA 5-yr zero adverse events, administer in home or facilities,


comparatively inexpensive to most modalities and incomes (controlled,
randomized, double-bind, positive industry-leading study results)

Published Microcirculation Research


Assessment of microcirculation
and the prediction of healing in
diabetic foot ulcers

Coronary microcirculation - the


new frontier in coronary artery
disease

Microcirculation in chronic
venous insufficiency

Impaired tissue perfusion

Role of renal microcirculation in


experimental renovascular
disease
The microcirculation in venous
hypertension

The microcirculation as a
therapeutic target in the
treatment of sepsis

Microcirculation in hypertension A New Target for Treatment

Microcirculation in obesity - an
unexplored domain
Microcirculation in skeletal muscle
Microvascular dysfunction in
obesity

Published CO2 Research

Promising previous results using carbon dioxide to trigger peripheral vasodilation

Duling14 found an increase in perivascular PO2 and arteriolar diameter in hamster cheek pouch after
bathing the tissue in CO2

Hartmann et al. bathed lower extremities in CO2-enriched water and measured an increase in PO2 by
10%, while vasomotion by laser Doppler increased 300%. Some subjects had mild peripheral artery
disease. They concluded the Bohr effect resulted in better oxygen utility 15

In a subsequent investigation by the same authors using the same methods, they found an
improvement in dorsal foot TcPO2 and pain-free walking distance in claudicants

Savin et al.12 used administration methods similar to that described in a study with D'OXYVA in 10
subjects with peripheral artery disease and claudication. Femoral blood flow, tibial pressure, and
TcPO2 in the foot were significantly increased after skin exposure of CO2 gas

Fabry et al.16 randomized 62 patients to transdermal CO2 or room air for 18 consecutive days. In the
experimental group, there was an increase in great toe arterial pressure, a 20% increase in baseline
PO2, and improvements in vasomotion. These effects continued at 3- and 12-month follow-ups.

Toriyama et al.17 studied the effect of CO2 bathing in 83 limbs with critical ischemia and achieved limb
salvage in 83% without surgery. They concluded that peripheral vasodilation from CO2 bathing
resulted from an increased parasympathetic and decreased sympathetic activity.

Signaling Gas Molecules


Carbon dioxide is one of the mediators of local autoregulation of blood
supply. If its levels are high, the capillaries expand to allow a greater blood
flow to that tissue.
Hemoglobin, the main oxygen-carrying molecule in red blood cells, carries both
oxygen and carbon dioxide.
However, the CO2 bound to hemoglobin does not bind to the same site as oxygen. Instead, it combines
with the N-terminal groups on the four globin chains. However, because of allosteric effects on the
hemoglobin molecule, the binding of CO2 decreases the amount of oxygen that is bound for a given partial
pressure of oxygen.

The decreased binding to carbon dioxide in the blood due to increased oxygen
levels is known as the Haldane Effect.
It is important in the transport of carbon dioxide from the tissues to the lungs.

Conversely, a rise in the partial pressure of CO2 or a lower pH will cause


offloading of oxygen from hemoglobin, which is known as the Bohr Effect.

Published Study - Diabetic Foot Global Conference


Los Angeles, CA - March 21-23, 2013

D`OXYVA Study Design


Subjects:
6 subjects with diabetes
8 subjects without diabetes
Treatment:
The subjects thumb was inserted
into the D`OXYVA device and
bathed in CO2 water/gas vapor for
5 minutes.
Measurements:
Brachial blood pressure

Vasamed SensiLase
Skin Perfusion Pressure

Skin perfusion pressure in the toe

5 minutes pre-treatment
5 min post-treatment
30 minutes post-treatment
60 minutes post-treatment
120 minutes post-treatment
240 minutes post-treatment

A graph displays pressure and


perfusion during cuff deflation and
indicates the pressure at which
skin perfusion is found to return.

Microvascular Treatment Breakthrough


Transdermal delivery of gaseous CO2 offers distinct advantage of increasing SPP, a
reliable predictor of wound healing7, 44
5-min CO2 immersion of thumb demonstrated significant increase in measures of
remote skin microvascular function/perfusion in toe, suggesting improving
peripheral wound healing
Effects evident at all periods up to and including last test period at 240-min postexposure
Clear SPP, SPP/SBP ratio increase, SBP, DBP decrease continued 4 hours posttreatment
Differences in skin perfusion, blood pressure responses detected between
diabetic, non-diabetic subjects requires further examination in larger studies

Transdermal delivery of CO2 to the thumb


promotes sustained huge blood flow at the foot
Diabetic (n =6)
Non-Diabetic (n=8)

50

Change in SPP (mmHg)

*
40

30

20

10

-5 5

30

60

120

Time (minutes)

240

How Transdermal CO2 Delivered at the Thumb Causes


Blood Flow Increase to the Foot?

1. Neural Signals

Metaboreflex

2. Hormonal Signals

Epinephrine
Angiotensin

3. Tissue Signals

Adenosine
Potassium

}
Source: Prof. Judy M. Delp, PhD

Discussion
Rogers et.al., found transdermal CO2 with D`OXYVA in a localized area produced
a sustained, remote vasodilation, and a lowering of systemic blood pressure

Findings share some similarity with hemodynamic changes occurring following


acute bout of exercise, in which both neural, vascular components contribute to
sustained decrease in vascular resistance, blood pressure persisting after
cessation of exercise18
Rogers et.al., recorded that period of sustained vasodilation in response to
transdermal CO2 was heightened in diabetics

Interestingly, in hypertensive individuals, post-exercise hypotension period


magnitude and duration is greater as compared to normotensive individuals18, 19

Discussion (cont.)
Paradoxically, Rogers et.al. findings in diabetics and previous findings in
hypertensive patients post-exercise imply, sensitivity to signals mediating
cardiovascular responses increases in patients with pre-existing cardiovascular
dysfunction19
Sustained systolic blood pressure decrease occurs post-exercise and after CO2
delivery, suggesting neural mechanisms contribute to observed reduction in
systemic vascular resistance
Roles of efferent sympathetic nerve activity18-20, afferent nerve activity from
muscle21-24, baroreceptor reflex20, 23 in mediating post-exercise hypotension
remain controversial
Neural mechanism(s) could contribute to changes in skin SPP, systolic blood
pressure, induced by exposure to transdermal CO2 with D`OXYVA

Studying Autonomic Nerve Activity


Studies to monitor heart rate, heart rate
variability, sympathetic nerve activity during/after
D`OXYVA transdermal CO2
Fully assessing autonomic nervous system role(s)
in mediating sustained SPP, systolic blood pressure
increases reported in initial study

THE AUTONOMIC NERVOUS SYSTEM


CONTROLS INTERNAL BODY PROCESSES:

Blood pressure
Heart and breathing rates
Body temperature
Digestion
Metabolism (thus affecting body weight)
The balance of water and electrolytes
(such as sodium and calcium)
The production of body fluids (saliva,
sweat, and tears)
Urination
Defecation
Sexual response

THE AUTONOMIC NERVOUS SYSTEM HAS


TWO MAIN DIVISIONS:
Sympathetic
Parasympathetic

Randomized Trial
Penn State University, PA

The Effect of Transdermal CO2 Diffusion on Sympathetic Nerve Activity and Vascular
Responses in Humans
Phase I, randomized, placebo-controlled, double-blind human clinical trial on 13 healthy subjects

Goal: Determining the effects of transdermal CO2 diffusion on the SYMPATHETIC


NERVOUS SYSTEM, VASCULAR BEDS is important in determining its efficacy for use as
treatment in chronic conditions, disease states

Method: Examine MUSCLE, SKIN SYMPATHETIC NERVE ACTIVITY, RENAL, CORONARY,


SKIN, LEG BLOOD FLOW, before, during, and 30 minutes after transdermal CO2 diffusion
in healthy subjects

Results: Sympathetic nerve activity to skeletal muscle appears not affected,


sympathetic bursts decline during delivery, sympathetic nerve activity to the skin in the
leg did not change during delivery but increased 30 minutes after, which is associated
with skin blood flow changes. The study had no adverse events, no toxicity reported.

Principal Investigator: CHESTER A. RAY, PhD, Department of Medicine, The Heart &
Vascular Institute, College of Medicine, Pennsylvania State University, U.S.A.

Randomized Trial
Penn State University, PA

Studying Autonomic Nerve Activity


Dr. Yen - Taipei Medical University, Taiwan
Subjects: Normal Humans
Both genders, age 18+, no history of respiratory or vascular disease
Recruit from companies and schools

Data Collection:
General information
Effects:

Baseline

Vital sign
Heart Rate Variability (HRV)
ETCO2
0 min
5 min
TcPO2

D`OXYVA
5-min treatment

30 min

60 min

General Information
Male

Female

Total

10

13

Average

Min

Max

Age

32.512.7

23

60

height

1697.3

155

179

weight

65.910.1

47

80

Studying Autonomic Nerve Activity


Results
Increase oxygen concentration and lower carbon
dioxide concentration in blood at 30 mins. after
treatment, and may persist over 60 mins.
Tend to decrease RRIV, stabilize overly-high heart
rate variation, reduce the risk of cardiac arrhythmia
Balanced sympathetic and parasympathetic tone;
this effect may be due to parasympathetic extend

Respiratory Results
(SpO2)
98
97.8
97.6
97.4
97.2
97
baseline

5 min

30 min

60 min

30 min

60 min

(ETCO2)
48
46
44
42
40
38
36
baseline

5 min

Heart Function
(Heart Rate)

R-R(RRIV)

100

300

90

250
200

80

150
70

100

60

50

50

0
baseline

5 min

30 min

60 min

baseline

5 min

NN(SDNN)
70
60
50
40

30
20
10
0
baseline

5 min

30 min

60 min

30 min

60 min

Autonomic Nervous System Function


(SYM)

(VAG)

30

1.2

25

20

0.8

15

0.6

10

0.4

0.2

0
baseline

5 min

30 min

60 min

baseline

5 min

(Balance)
30
25
20
15
10
5
0
baseline

5 min

30 min

60 min

30 min

60 min

Autonomic Nervous System Function


(SYM Modulation)

(ANS)

1.4

2.5

1.2

1
0.8

1.5

0.6

0.4

0.5

0.2
0

baseline

5 min

30 min

60 min

baseline

5 min

(ANS Age)
1.4
1.2
1

0.8
0.6
0.4
0.2
0
baseline

5 min

30 min

60 min

30 min

60 min

Discussion Autonomic Nervous System


Toriyama et al.17 studied the effect of CO2 bathing in 83 limbs with
critical ischemia and achieved limb salvage in 83% without surgery.
They concluded that peripheral vasodilation from CO2 bathing
resulted from an INCREASED PARASYMPATHETIC and DECREASED
SYMPATHETIC activity.
Prof. Chet A. Ray studied the effect of transdermal CO2 delivery
with DOXYVA during delivery and 30 minutes after and found no
effect or a DECREASE ON SYMPATHETIC nerve activity and an
INCREASE IN PARASYMPATHETIC activity in healthy subjects.
Dr. Yen studied the effect of transdermal CO2 delivery with
DOXYVA during delivery and 5, 30, 60 minutes after and found it
that balanced sympathetic and parasympathetic tone and this
effect may be due to the resulting parasympathetic extend

Discussion Summary
DOXYVAs SOLITION through skin pores and tissue without breaking skin barrier or
harming skin; detected no increase in blood or tissue CO2 during delivery and a
significant sustained O2 increase trending to 100% SpO2 in 10 minutes, and an
equally large decrease of CO2 in all subjects and in all studies.
Peripheral CO2 receptors in ANS sense increase concentration locally, signal nerve
activity.
Carbonic anhydrase, oxygen curve shift (Bohr effect), vasodilation detected in all
subjects for hours after delivery in all studies.
DOXYVA increases parasympathetic and decreases sympathetic nerve activity in
great majority of subjects for at least 60 minutes in a study.
DOXYVAs impact on microcirculation concurs with all published research in the
field explaining shunting that it increases microvascular blood flow and
vasomotor activity in areas deprived of it such as diabetic foot ulcers, ischemia,
vascular, burn and trauma wounds and decreases it where too much blood flow is
detrimental such as a cancerous tumor.

Diagnostics Used in D`OXYVA Studies


Moor Instruments

SenTec

Vasamed

Hitachi

Masimo

WeGene

Case Study Military Hospital


Taipei, Taiwan
Post-D`OXYVA (2x daily)
Pre-D`OXYVA
Lower
extremity
arterial
embolism. 1st
catheter poor
results, 2nd
cannot pass
to knee. 6-mo
on painkillers,
morphine,
hormones;
enlarging
wound.

Case Study Dr. Benjamin Sinappan


Kuala Lumpur, Malaysia
Post-D`OXYVA (3-wk 2x daily)
Week 1

Week 2

Week 3

Case Study Dr. Benjamin Sinappan


Kuala Lumpur, Malaysia
Pre-D`OXYVA

Post-D`OXYVA (1x on affected area)

Pre-D`OXYVA: Lower extremity chronic venous insufficiency (CVI).


6-mo on painkillers, morphine, hormones; enlarging varicose vein.
Hypoxia-inducible factor pathways are thought to play a key role.

Case Study - University of Szeged, Hungary


Pre-D`OXYVA (2 Mo. Hospital)

Post-D`OXYVA (25 days 2x daily)

68-year-old male suffered forklift truck


accident, trimalleolar fracture with massive
soft tissue contusion and crural decollement,
extensive decollement was not realized and
treated adequately, septic, glycaemic status
unbalanced, skin necrotized around anterior
surface leg, medial malleoli and around heel.

16th Congress of the European Society for


Trauma and Emergency Surgery (ESTE)
May 10-12, 2015 Amsterdam, Netherlands

Presented by Prof. Endre Varga, MD


(habil), PhD (med)

Very drastic surgical


debridement, necrotised skin
removed, microbiological
analysis of swab wound
samples, mixed infection
(Enterobacter cloacae and
ludwigii, Acinetobacter sp.,
Proteus mirabilis and
Escherichia coli.), antibiotic
treatment. Every two days
surgical debridement, jet
lavage, no further necrotised
tissue 10 days after, 2-wk VAC,
Integra. Compliance dropped
off, psychological support as
he removed dressings,
surprisingly after 2 wks fly
larvae (Diptera:
Sarcophagidae) in skin graft
area.
Post-D`OXYVA: Walks with
crutches after 3-mo,
discharged.

Pilot Study Dr. Harikrishna R. K. Nair


Hospital Kuala Lumpur, KL, Malaysia

Successful Late Stage Gangrenous Diabetic Wound Pilot Studies were


Recently Completed at HKL with D`OXYVA that Launched Randomized
Diabetic Foot Ulcer Trials
The results of the study clearly demonstrated SIGNIFICANT QUALITY OF
LIFE BENEFITS AND SPEEDING UP WOUND HEALING using Circularity's
D`OXYVA proprietary, noninvasive, handheld transdermal delivery system
as an adjunct therapy.
Results: All four (4) volunteers enrolled in the pilot study experienced
SIGNIFICANT REDUCTION OF PAIN, TYPICALLY FROM AN 8 ON THE VISUAL
ANALOG SCALE FOR PAIN (VAS SCALE) DOWN TO 1 in a week or two.
Results: All volunteers saw an INCREASE IN APPETITE, MOOD AND
MARKEDLY BETTER SLEEP. Patients suffering from stage IV gangrene
experienced improvements in wound healing within a few weeks. No
adverse events of any kind were reported by the subjects.

Randomized Clinical Trial


Dr. Harikrishna R. K. Nair, HKL - Malaysia

Randomized clinical trial; 60 volunteers with stage II diabetic


ulcer wounds
Goal: Design proper dosing and length of treatment with
D`OXYVA to maximize benefits and better determine time of
healing
Method: Measure various parameters for wound healing
using FDA-cleared noninvasive diagnostics, including:
continuous and noninvasive capillary blood flow volume change,
continuous and noninvasive real-time monitoring of
transcutaneous CO2 partial pressure (PCO2), functional oxygen
saturation (SpO2), pulse rate (PR), pulsation index (PI), heart rate
(HR), and perfusion index (PI).

The Effect of Deoxyhaemoglobin Vasodilator in Heart Failure Patient:


A Case Report - Zurairie, M1, Afandi, M2, Filza, IA3

1Wound

Background: WHO projects the largest increases in cardiovascular disease worldwide are occurring in
Asia. In the heart failure patients, the risk of death increasing particularly with left ventricular ejection
fraction (LVEF) less than 40%. There is resistance in practicing the implantation of defibrillator to reduce
sudden cardiac death among the Asian populations and there is less option could be taken to increase
the LVEF.

We are reporting a case of a 62 year-old gentleman, with history of four times angioplasty done for
vessels disease with poor LVEF (37%) and the first experience in Malaysia with deoxyhaemoglobin
vasodilator therapy in increasing the LVEF. After a month of therapy, our experience with dosage and
frequency of the transdermal carbon dioxide (CO2) delivery as well as patients LVEF before and after the
treatment were documented.

Results: After 4 weeks, the patient clinically improved from heart failure symptoms. Objectively, his LVEF
was increased from 37.17% to 46.99% and the PaO2 increased from 84.5mmHg to 104.7mmHg

Care and 2Cardiothoracic Surgical Unit, Hospital Raja Perempuan Zainab II, Malaysia
3Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Malaysia

Case Study - Bangkok, Thailand


Pre-D`OXYVA (2-yr therapy)

Post-D`OXYVA (6-wk 2x daily)

Pilot Study Moor Blood Flow


Chulalongkorn University, Bangkok, Thailand

Equine Study Moor Cont. Blood Flow


Esler Arabians, San Francisco, CA
~100-300%
capillary flux
increase
60-90 min
Post-D`OXYVA
(1x) in 5 horses
No change in
control group of
5 horses

Case Study - Moor / Masimo iSpO2


Taipei, Taiwan
400% peak increase in Perfusion Index (PI)
30 min Post-D`OXYVA (1x) same time both
hands, both Moor & Masimo diagnostics

The moorFLPI-2 blood flow imager uses the


laser speckle contrast technique to deliver realtime, high-resolution blood flow images,
providing outstanding performance in a wide
range of pre-clinical and clinical research
applications.
Source: Moor Instruments

The iSpO2
Masimo
Personal
Health app
coupled
with your
iSpO2 pulse
oximeter
allows you
to track and
trend your
blood
saturation
(SpO2),
pulse rate
(PR), and
Perfusion
Index (PI).
Source: Masimo

Highlighted User Feedback


My heartfelt thank you to InvisiDerm management
for their support before and after my heart attack.
I firmly believe the collateral capillaries that have formed
on my heart, bypassing the damage, is a direct result of my
using the (D`OXYVA) system. I'm very happy to report an
increase from 15% to an estimated 30% in the injection
fraction number (I believe that is the correct name) that
has occurred since I left the hospital. The generous gift of
treatment cartridges has allowed me to increase my daily
usage to 2-3 times per day and the cardiologist now says I
may be a candidate for bypass surgery. I will keep the
company informed of my progress. Again THANK YOU
INVISIDERM for making it possible for me to write this
letter.

Highlighted User Feedback


Scar tissues are healing
As an Esthetician, I noticed certain scar tissues are healing and the cut
that I have is healing really fast. I am very happy with it.
Better vision, breathing and sleeping
"My vision seems to be a little clearer. I have been experiencing
chemically induced asthma from noxious fumes from a Nail Salon next
door. I noticed that when I am struggling to breath, I will do an
application and my ability to breath is noticeably better. Also, I am
sleeping better now."
Better metabolism, weight loss, sex drive
I have found that after only two weeks of using the D'OXYVA system
daily that my metabolism has increased and is helping me to lose
weight. My sex drive has increased and I am sleeping better
throughout the night.

In-facility Patient Needs


PRE-HEALING
Average Use (e.g., Stage 1-3)
1 device per 10 patients
2 boxes (25 cartridges) per patient per month

Severe cases (e.g., late Stage 4)


1 device per 5 patients
3-4 boxes per patient per month

POST-HEALING (e.g., wound closure, post-operative)


1 device per 20 patients
1 box per patient per month

Benefits to Health Facilities


Faster, more complete healing, recovery; better patient
outcomes
Faster patient discharge ~ half the time as usual
Significantly less readmissions

Significantly lower cost of care


Significant savings on other therapies

Market Drivers for D`OXYVA


Diabetes, cardiovascular, arthritis, COPD complications creating an epidemic
globally with uncontrollable costs, Asia is hardest hit
Several major long term trends are reshaping the healthcare industry
worldwide, DRIVING THE DEMAND FOR D`OXYVA:
Movement to outpatient setting; care for wounds, disorders facing increasing
demands for EXPEDIENCY, NON-INVASIVENESS, LOW COST
Increasing demand for post hospitalization care; driving need for
HOME BASED WOUND CARE AND INEXPENSIVE HOME HEALTH options

Increasing role of TELEMEDICINE & TELEDIAGNOSTICS tracking patient progress &


satisfaction, making patient comfort & quick recovery top priority
SHRINKING HEALTHCARE BUDGETS and reimbursement for hospital stays

Circularity Healthcare at a Glance


By expert opinion, Circularity Healthcare is bringing about a
change in the standard of care, drug delivery, circulatory,
and neurological fields
Attracted top scientific and medical experts in a dozen
countries
Obtained critical clinical evidence and user feedback with
an outsized safety and efficacy record
Zero adverse events (4 years), hundreds of thousands apps

Circularity Healthcare at a Glance


ISO13485:2012 certified manufacturer since 2015
CE-marked drug delivery device since 2016
FDA-cleared pharmaceutical CO2 (Medical CO2)
Upcoming approvals for chronic disease treatment
Entry in dozens of countries worldwide
4 years five star customer satisfaction rating
Oncology, endocrinology, cardiovascular, respiratory, dermatology, etc.

Circularity Healthcare at a Glance


Active in 50 countries, in North America, Europe, and Asia with joint ventures,
distribution channels
Established business model in the U.S. and internationally, validated by and
marketed with leading FDA-cleared diagnostics
Affordable applications for the vast majority of the population with one of the
lowest risk profiles on the market
Obtained uniquely strong, sizeable patent portfolio in over 70 countries coupled
with several technological, legal, and regulatory safeguards
Strong clinical research, product, technology, research and development program
with years of advances in store

Thank You for Your Attention

Ecommerce website:
DOXYVA.com
Corporate website:
CircularityHealthcare.com
Social Media:
Facebook.com/DOXYVA
Video:
Youtube.com/CircularityDOXYVAS.com
Toll Free Phone:
+1-855-5DOXYVA
Email:
info@doxyva.com
info@circularityhealthcare.com

Legal Disclaimer

Notice! Medical Carbon Dioxide is manufactured and delivered under applicable standards per each
country's regulatory requirements. In the United States, the Food and Drug Administration has cleared
the use of Medical Carbon Dioxide for the route of inhalation for humans but not yet for transdermal
delivery with D`OXYVA. Transportation of Medical Carbon Dioxide via any postal or courier service
requires certification for handling Dangerous Goods (HAZMAT) by the U.S. Department of Transportation
(DOT). Use of unapproved substances and products may be illegal, cause serious injury, and even death!

Warning! Ask your physician before using D`OXYVA FOR MEDICAL AND CLINICAL RESEARCH PURPOSES,
prescription only. The D`OXYVA transdermal delivery device holds a growing number of Class I (low risk)
licenses around the world. Use for non-medical purposes is available over-the-counter (OTC) and in
various retail stores online and offline. Circularity's novel D`OXYVA patented transdermal drug delivery
pathway with FDA-cleared Medical Carbon Dioxide (UN1013) has not been evaluated yet by the U.S.
Food and Drug Administration (FDA) and is not intended to diagnose, treat, cure, or prevent any disease.
The information provided herein is for educational and research purposes and is not intended to replace
medical advice.