Circularity - Science Publications: General Public Patients

Index:
Title: Behind the Science
Let's talk about your circulatory system
Your heart and vascular system
Outstanding clinical research results
In humans
In domestic animals
What do healthcare professionals think of DOXYVA?
Bibliography

Title: Behind the Science

------------------------

The science behind DOXYVA (deoxyhemoglobin vasodilator) is extraordinary and bright, and
its potential to positively impact our general health and quality of life could revolutionize
holistic medicine. When our body is out of balance (loss of homeostasis), diseases follow.
Several factors that can cause loss of homeostasis are stress, alcohol, starvation, overheating,
malnutrition, loss of sleep, lack of oxygen, excessive exercise, and small fluid ingestion.
DOXYVA aims to deliver a highly concentrated CO2 vaporized solution that will help our body
restore its homeostasis through the improvement of blood circulation in our body, thereby
targeting organ blood microcirculation (micro vascular system). It is through microcirculation
that our organs receive their nutrients and oxygen and remove waste in order to maintain a
healthy and balanced cellular environment.

Let's talk about our circulatory system

Standard organ functions, cell functions, and metabolism rely on our circulatory system for a
constant delivery of oxygen, nutrients, hormones, electrolytes, and water and for metabolic by-
product (waste) removal. Our circulatory system is a complex plumbing network composed of:
heart, a powerful pump in charge of maintaining constant blood pressure throughout the body
and vascular system, and a tubing network in charge of distributing blood and its nutrients to
our bodys organs.

As we age and develop health conditions such as diabetes, high blood pressure, digestive
disorders, pain, stress, and grief, our circulatory network loses its ability to deliver adequate
blood flow where it's needed the most. This sequence of events causes our body to lose its
capability to self-heal.

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare

Circularity - Science Publications: General Public Patients

Our heart and vascular system

Our heart is a two-sided pump connected to a complex vascular system (blood vessels)
arranged in series and parallel circuits, similar to a home plumbing network. Our bodies have
different size arteries in charge of delivering clean, O2 saturated, and nutritive blood to our
organs and veins, which are themselves in charge of carrying used blood with poor nutrients
and low O2 levels from the organs. Our vascular system works in a way so that the great arteries
have little impact on blood pressure, but small ones control almost 70% of the blood flow
resistance (blood pressure). For example, a person can have a 50% occlusion of a large artery
and be totally asymptomatic.

In other words, the microcirculation system helps our bodies to have uninterrupted blood flow
where its needed the most.

The microcirculation resides within our organs (liver, kidney, pancreas, brain, skin, etc.) and is
responsible for the regional blood flow (the average adult blood volume in our body is 5.5
liters) to each organ. The blood vessels that form the microcirculation are less than 100m in
diameter, and each adult organ can have more than 2 miles of capillaries inside it. Inside adult
organs, the microcirculation vessels consist of capillary bed units. Each capillary bed unit is
composed of:

arteriole (blood from the heart), which is responsible for delivering nutrients and oxygen
meta-arterial (potential capillary blood bypass route), which shunts blood to other capillary
beds
precapillary sphincter (controls blood flow), which helps to close and open the arterioles
diameter as a response to chemical and physical stimuli
venules (blood return to the heart), which is responsible for carrying metabolic waste and
poorly oxygenated blood from the organ

Each capillary bed is in charge of exchanging small molecules between organ cells and the blood
and maintaining a healthy cell microenvironment (homeostasis) within the body.

To be efficient, our body regulates organ blood flow according to its metabolic needs. There is
still debate regarding the exact mechanism that governs the process, but there is no discussion
regarding the bodys chemicals and protein protagonists that mediate and link vascular blood
flow (vasodilatation) to cellular metabolisms, such as nucleotides (DNA building blocks), nitric
oxide, pH, and CO2.

The vascular system reacts to metabolism by-product concentration by deciding where to

allocate resources and remove waste. However, with time and with the accumulation of
microcirculation damage due to bad health care habits, poor diet, and sickness, our bodies lose
their ability to maintain homeostasis. When this occurs, our bodies fail to heal properly, and

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare

Circularity - Science Publications: General Public Patients

disease follows, such as pain, acidosis, diabetes, infections, and poisoning, among other
conditions.

Under these situations, our body needs help to achieve homeostasis and wellness. With that in
mind and taking advantage of our bodys healing power, Circularity Healthcare developed
DOXYVA (deoxyhemoglobin vasodilator). DOXYVA is a class 1, low-risk medical device; it uses
the natural properties of CO2 (an FDA-cleared drug) to activate our bodys chemoreceptor and
increase organ blood flow through the microcirculation while promoting oxygen delivery in
capillary beds and organ tissue.

DOXYVA technology used by Circularity Healthcare is a novel method of delivery of

supersaturated CO2 and water vapor to our skin. The skin is the largest organ in our body and
possesses a high concentration of microcirculation, particularly in our hands. The high level of
vascular beds and pores is what makes it the ideal route for CO2 delivery.

Our bodies produce and exhale CO2, and it is capable of absorbing it through the skin. The skin
can absorb CO2 100 times more efficiently than water. Once CO2 enters our system, the
following physiologic changes occur:
Dilatation of capillary arteriole sphincter (decreased capillary resistance).
Increased blood flow through the microcirculation (organs).
Adaptive modifications in the circulatory system that promote improved blood flow.

When all these body adjustments occur inside the body, we start to perceive the positive
impact of the DOXYVA medical devices efficient delivery of highly concentrated CO2, including
more energy / vitality, concentration, decreased pain sensation, and improved blood flow.

Outstanding clinical research results

More than two dozen research projects have been performed to test DOXYVAs potential and
capabilities to help patients obtain wellness. We have tested the DOXYVA medical devices
efficiency, tolerability, and safety to deliver a highly concentrated but gentle CO2 mist to our
body through the skin and to prove beyond doubt its reproducibility. To do so, we measure body
CO2 concentration before and after treatment and the expected physiologic body response to
this treatment. In addition, we have partnered with healthcare leaders and clinicians to perform
independent research studies.

Research end points:

1) Safety and tolerability
a. No patient side effects have been recorded by our clients to date in our
sponsored research projects, and none have been documented elsewhere.

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare

Circularity - Science Publications: General Public Patients

We encourage you to discuss with your healthcare professional

whether DOXYVA medical device is right for you.
b. Measured transcutaneous carbon dioxide (TcPCO2)
Within the first 5 minutes of DOXYVA application, TcPCO2 increases
in our body followed by a declining slope that lasts approximately 240
minutes until it returns to base line values.
In healthy individuals, DOXYVA does not increase pCO2 beyond our
bodys buffer manageable range. This indicates high level of safety.

2) Efficient CO2 delivery

a. Measured blood perfusion index (PI)
i. All research project results consistently record a significant increment
in PI in 100% of participants within the first 5 minutes of application,
peaking 60 minutes after application. 60 minutes after treatment until
240 minutes (our largest time-period evaluation after application), PI
decreases slowly to baseline levels.
1. PI studies on diabetic patients have demonstrated a larger
response to CO2 than in non-diabetic healthy individuals. Our
studies have recorded that PI change (from baseline) in
diabetic patients is double the PI change recorded in healthy
patients. (Graph 1)

Graph1- Skin perfusion index (SPP) in healthy and diabetic participants

vs. time after using the DOXYVA medical device

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare

Circularity - Science Publications: General Public Patients

b. O2 concentration
DOXYVA medical device application has consistently led to increased
free O2 molecules in our patients blood streams. The effective
transdermal CO2 delivery allows our body to increment O2 availability
through the Bohr effect. This helps hemoglobin cells to unload O2
more easily by decreasing their affinity.

c. Blood pressure
All research projects performed to date have consistently recorded a
significant decrease in systolic pressure (from the heart) and diastolic
pressure (return to the heart). These results have been consistent
throughout all study time periods up to 240 minutes (our largest time-
period evaluation after treatment).

d. Diabetic ulcer
A research project focused on DOXYVAs impact on diabetic ulcers
has recorded significant wound healing changes such as significant
granulation tissue and an improved ulcer border as soon as 1 week
into the DOXYVA treatment plan. (Image1)

Image 1

After 7 days of
DOXYVA
(1x per day);
same wound
dressing as
before

e. Sports
Amateur and professional athletes are always searching for ways to
improve cardiovascular function and increase the vascular transport
capacity of skeletal muscle. This is because better vascular transport
capacity translates to more O2 and nutrients being delivered to our
muscles, and this means better performance in the field.

DOXYVA research focused on the superficial skeletal muscles

perfusion index (PI) has recorded excellent results. The most
important findings demonstrate that participants using DOXYVA
double their PI compared to the control group.

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare

Circularity - Science Publications: General Public Patients

f. Blood alkalinity
Use of DOXYVA has consistently recorded an improvement in local
cellular homeostasis. It has the potential to improve body pH values
by promoting an alkaline ambiance. A slightly alkaline
microenvironment within our bodies promotes good health and
optimal body organ performance.

In humans

The Circularity Healthcare research teams and partners have successfully proved that patients
who use DOXYVA have experienced CO2 body-healing effects such as improving
microcirculation blood flow in the skin and in superficial skeletal muscles, blood pressure
improvement (systolic and diastolic), and success in improving hard-to-treat ulcers, such as
diabetic ulcers, in all participants.

In domestic animals

Healthy skin, hair, and fur growth depends on a proper balance of nutrient delivery, waste
removal, and oxygenation. D'OXYVA delivers outsized benefits by improving skin
microcirculation and oxygenated blood supply delivery. By improving the animal blood flow
through the microcirculation, D'OXYVA promotes healthier hair follicle growth and the bodys
ability to heal underlying health conditions that diminish the animals fur shine. Also, it has the
potential to accelerate the skin healing process after surgery and prevent wound dehiscence.

Equine (horse) studies have shown that DOXYVA has managed to deliver CO2 through their
skin, and researchers have been able to identify CO2s natural healing capabilities in the horses
bodies.

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare

Circularity - Science Publications: General Public Patients

What do healthcare professionals think of DOXYVA?

Judy M. Delp, PhD, professor of physiology and functional genomics at Florida State
University, stated:

"The DOXYVA device is safe and can be administered at home. 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."

Dr. Jim Bledsoe, PhD, nutritional scientist, stated:

"I have been using the D'OXYVA for past 4 years. After I started using the D'OXYVA, I felt
a major improvement in my breathing because my sinus issues had cleared up. Second, I
stopped snoring. After about 4 months, I realized that my muscles felt better and I was
gaining my muscle mass back."

Prof. Ito Puruhito, Thoracic, Cardiac and Vascular Surgeon, Medical Faculty, Universitas
Airlangga, Surabaya, Indonesia, in a recent interview at the International Wound Care
and Biotherapy Conference in Kuala Lumpur, stated:

I immediately began testing DOXYVA on both myself and my patients and found
outstanding results. Patients wound healing times decreased, and difficult non-healing
wounds began responding and improving in ways they had not previously.
In my personal use, the increased blood oxygenation levels left me feeling a greater
sense of energy and well-being. And thats important for someone my age with a full
slate of patients and academic responsibilities!
The results were so strong it became clear that I needed to undertake a more formalized
study of the benefits of DOXYVA. As a researcher it is one thing to observe results in
your patients, but another to experience them in your own body. With DOXYVA
transdermal technology, I had both!

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare

Circularity - Science Publications: General Public Patients

Bibliography
CELLULITE AND CARBON DIOXIDE BATH. (2009, may 9).
Chester A. Ray, P. (2013). PENN STATE, D'OXYVA STUDY-- PRELIMINARY RESULTS. The
Effect of Transdermal CO2 Diffusion on Sympathetic Nerve Activity and Vascular
Responses in Humans. PENDING.
Dogaru Gabriela, R. A. (2015). THERAPEUTIC EFFECTS OF CARBONATED MINERAL
WATERS IN CARDIOVASCULAR REHABILITATION . Balneo Research Journal, 36-
39.
Evaluation of a Novel Medical Device (Carbothera) in the Prevention of Foot Ulcers in Patients
With Critical Limb Ischemia and Undergoing Hemodialysis. (2014). Evaluation of a Novel
Medical Device (Carbothera) in the Prevention of Foot Ulcers in Patients With Critical
Limb Ischemia and Undergoing Hemodialysis.
HRV. (2016). HRV STUDY TAIWAN . HRV STUDY TAIWAN POWER POINT INFORMATION .
TAIWAN .
Maria Vitria Carmo PenhavelI, V. H. (2013). Effects of carbon dioxide therapy on the healing of
acute skin wounds induced on the back of rats1. Acta Cirrgica Brasileira , 334- 339.
Mitsubishi-Rayon-Cleansui. (2014). Evaluation of a Novel Medical Device (Carbothera) in the
Prevention of Foot Ulcers in Patients With Critical Limb Ischemia and Undergoing
Hemodialysis . University of Manitoba : ClinicalTrials.gov Identifier: NCT02239419.
Norbert Kiss1, J. M.-D. (2016). LEE ROGERS STUDY JOURNAL . Transdermal Delivery of
Carbon Dioxide Boosts Microcirculation in Subjects with and without Diabetes .
Nouvong, J. S. (n.d.). Assessment of Microcirculation and the Prediction of Healing in Diabetic
Foot Ulcers . Western University of Health Sciences, College of Podiatric Medicine
United States of America: www.intechopen.com.
Schmidt, K. (n.d.). Carbon Dioxide Bath (Carbon Dioxide Spring). Bad Nauheim, Germany:
Center for Clinical Research in Rheumatology, Physical Medicine and Balneotherapy;.
V. VARLARO, G. M. (2007). Carboxytherapy:effects on microcirculation and its use in the
treatment of severe lymphedema A review. ACTAPHLEBOL, 1- 8.

Created by: Dr. Rafael Quintana, MD for Circularity Healthcare