3. Ozone
History
• Ozone was discovered in 1785 by Dutch physicist Martinus Van Marum
• In May 1840 that the German chemist Christian Friedrich Schönbein
synthesized it
• In 1900, medical ozone was used in the U.S. by Nikola Tesla by using high
voltage, high frequency, low amperage alternating-current (AC) system
• The first medical application seems to have been the use of ozone for treating
gaseous, post-traumatic gangrene in German soldiers during the 1st world
war.
4. Ozone
Introduction
• Ozone is an unstable, colorless, irritant gas with a pungent odor which has a strong
oxidising power as well as good antiseptic, disinfectant, and antiviral properties.
• It is chemically the triatomic, allotropic form of oxygen,
• Having the chemical symbol O3 ,
• Molecular weight of 48 kDa.
• Ozone, under standard atmospheric temperature and pressure, is an unstable gas
with a half-life of 20 minutes that decomposes readily into molecular oxygen.
• For injection, it is always freshly prepared before administration, wherein only ozone-
resistant syringes should be used.
5. PREPARATION OF OZONE
Methods of preparation of ozone
• Generation of ozone can be achieved by:
• (1) UV radiation,
• (2) An electrochemical process
• (3) Corona discharge
• (4) Cold plasma generators are now-a-days available, which is long-lasting
than other generators.
} • a low ozone output and a poor
regulation of production
6. Methods of preparation of ozone
Commercial Ozone Production from UV Light
Advantages of UV Ozone Generator
• Simple Construction – only a UV lamp with
ballast and a fan
• Low cost – due to simple construction
• Lower nitric oxide production
Disadvantages of UV Ozone Generator
• Low ozone output – g/hr
• Low ozone concentration – less than 1% by
weight
• Bulbs and ballasts will need to be replaced
7. Methods of preparation of ozone
Commercial Ozone Production from Electrical Discharge
The most common method of producing ozone commercially and industrially is electrical
discharge, or corona discharge. A corona discharge is simply a di
ff
used spark through a dielectric
to spread out that electrical discharge to a large area for maximum e
ffi
ciency.
8. Methods of preparation of ozone
Commercial Ozone Production from Electrical Discharge
• There are many types and styles of corona discharge ozone generators. These go by many
names, but are fundamentally the same, using these components:
• -Corona cell using a dielectric
• -Dielectric material may be glass, ceramic, or quartz
• -Dielectric may be conical, or
fl
at plate
• -High voltage transformer to increase voltage of the electrical discharge
• -Power supply to regulate power to transformer
• -60Hz machines will only regulate the voltage to the transformer
• -High frequency machines (greater than 60 Hz) will regulate frequency and/or voltage to transformer
9. Methods of preparation of ozone
Ozone production from Corona Discharge
• Ozone is produced from electrical discharge, commonly referred to as a spark.
• This is one of the reasons you smell the “fresh” smell after a thunderstorm.
• Any electrical discharge, or spark will create ozone
• Dielectric Used to Create Corona: A single spark from an anode to cathode will
fi
nd a few oxygen molecules in-between and will produce some ozone.
However, if this spark is spread out over a greater area, more oxygen
molecules will be contacted. This is the reason for the dielectric barrier used in
an ozone generator to create a corona. Using a dielectric the spark is spread
over a greater area and creates a true corona.
10. Methods of preparation of ozone
Ozone production from Corona Discharge
• -Dielectric - material to di
ff
use the spark into a corona, these may be one of
the following materials
• Glass
• Ceramic
• Quartz glass is an ideal material to create electrodes
• Mica
• Other materials that are used are Kynar and Te
fl
on.
11. PREPARATION OF OZONE
Why Quartz glass is an ideal material?
• 1. It has no occlusions, impurities
• 2. It is impervious to the e
ff
ects of a high-energy
fi
eld
• 3. It is 100% resistant to the oxidative e
ff
ects of ozone.
يتآثر ال
شوائب
12. PREPARATION OF OZONE
Ozone Concentration: is determined by three parameters:
• 1. THE VOLTAGE: the final ozone concentration increases with the voltage,
albeit in a non-proportional manner.
• 2. THE SPACE BETWEEN THE ELECTRODES: this serves to modulate a
gradual increase of the ozone concentration.
• 3. THE OXYGEN FLOW: this is expressed as a volume of litres per minute (l/
min) and normally can be regulated from 1 up to about 10 l/min.
• The final ozone concentration is inversely proportional to the oxygen
flow; hence, per time unit, the higher the oxygen flow, the lower the ozone
concentration and vice versa.
.متناسبة غير بطريقة كان وإن
13. Parts of a Basic Ozone Generator
• 1. Power switch
• 2. Flow meter
• 3. Ozone ratio controller
• 4. Ozone indicator
• 5. Oxygen/air inlet port with replaceable
tube
• 6. Built-in syringe port with replaceable
fi
lter.
14. PREPARATION OF OZONE
Steps to Generate Ozone
• 1. The oxygen source is connected to the generator through the gas feeding tube
• 2. The oxygen
fl
ow is set at 0.5–1 L/min
• 3. The desired ozone concentration is set on the ozone ratio controller
• 4. The machine is turned on.
• 5. Ozone generation is usually indicated through the detection of a pungent smell
or by an indicator in some machines
• 6. The initial volume of the ozone is discarded and the rest is
fi
lled in ozone-
resistant syringes.
15. PREPARATION OF OZONE
Precautions must be taken during ozone generation:
• 1. It is essential that high concentrations of ozone are prevented from entering the air.
This is only possible if an external or internal catalytic ozone destruct is provided with
the ozone equipment. The best destruct units are those that use iron crystals and
avoid carbon, as it can cause explosions
• 2. The ozone generator is fed with oxygen from an oxygen cylinder or an oxygen
concentrator.
• Air contains 78% nitrogen and 21% oxygen. (the free oxygen molecule combines
with nitrogen to form nitric oxide, which is highly toxic).
• 3. Proper ventilation in the form of vents and exhaust fans should be present to
dissipate the heat (( The electrical energy is converted into heat.This heat should be
removed as it will cause rapid decomposition of ozone into oxygen.))
16. PREPARATION OF OZONE
Precautions must be taken during ozone generation:
• 4. Ozone should not be applied directly to the skin and eyes as it produces
dryness
• 5. Do not allow water to enter into the machine.
• 6. Use
fi
lters to prevent bacteria or any metal impurities to enter into the
syringe.
• 7. Do not breath directly as it can cause bronchospasm
17. PREPARATION OF OZONE
Properties of Ozone for injection
• Ozone is administered in the form of an oxygen-ozone gas mixture,
• medical ozone, at non-toxic concentrations varying from 1 to 40 μg of ozone
per milliliter of oxygen.
• Empirical studies performed in vivo on rabbits and in vitro on resected human
disk specimens have demonstrated that for intradiskal administration, the
optimal concentration of ozone per milliliter of oxygen is 27 μg.
18. Description of an Ozone Generator
• When an energetic force such as electricity or UV light is imposed on an
oxygen molecule,
• The two oxygen atoms are temporarily split into single oxygen atoms.
• Consequently, oxygen radicals are produced which bonds with oxygen
molecule to form Ozone.
• Ozone operates on the principle of oxidation.
19. Description of an Ozone Generator
• O2 molecules go into the generator and are exposed to an electric spark.
• Ozone is produced in a silent electrical discharge within which electrons with
su
ffi
cient kinetic energy split the O = O bond upon impact resulting in a
mixture of oxygen and ozone.
• Corona discharge type is the most common generator used for the
production of ozone because of the advantages like coste
ff
ectiveness and
the greater durability of the system.
• For the feed inlet, medical grade oxygen is used. When pure oxygen is used,
a higher concentration of ozone can be produced.
مكرر
20. Mechanisms of Action
• The action of ozone is due to the active oxygen atom released by the
breakdown of the ozone molecule.
• Ozone has a dose-related biological action.
• At high concentrations (30–70 µg/ml O2), it may cause alterations of tissue
structure.
• At medium concentrations (20–30 µg/ml O2), it seems to a
ff
ect the regulation
of the immune system.
• At low concentrations (<20 µg/ml O2), it improves the microcirculation.
21. Mechanisms of Action
• The dose of ozone is crucial and must not exceed the capacity of
antioxidant enzyme and glutathione to prevent accumulation of the
superoxide anion and hydrogen peroxide, which can cause cell membrane
degradation.
• Viebahn reported that the nontoxic concentration of ozone varies from 1 to 40
µg/ml of oxygen,
• and concentration of ozone for therapeutic purpose should not exceed 40 µg/
ml.
• The Total Ozone Dose Is Equivalent to the Gas Volume (ml) Multiplied by the
Ozone Concentration (mcg/ml)
22. Mechanisms of Action
• The Total Ozone Dose Is Equivalent to the Gas Volume (ml) Multiplied by the
Ozone Concentration (mcg/ml)
• As an example, for a volume of 100 ml blood, we use an equivalent volume of
gas (1:1 ratio) with an ozone concentration of 40 mcg/ml, the total ozone dose
is: 100 × 40 = 4,000 mcg or 4.0 mg.
23. CONTRAINDICATIONS
Absolute
• 1. Local or systemic infection
• 2. Coagulopathy and patient on anticoagulants without adequate
recommended drug free period
• 3. Lack of consent
• 4. Active hypothyroidism
• 5. Glucose 6-phosphate dehydrogenase (G6PD de
fi
ciency.
24. CONTRAINDICATIONS
Relative
• 1. Pregnancy
• 2. Patient not able to lie prone
• 3. Non-cooperative patient
• 4. Patient with severe cognitive dysfunction
• 5. Allergy to any of the drugs used for procedure
• 6. Unstable vital parameters
• 7. Previous surgery
• 8. Anatomical variation.
25. Toxicity
parts per million (ppm) A measurement of concentration on a weight or volume basis. Parts per million by mass is equivalent to
milligrams per liter (mg/L). Parts per million by volume is a common way to measure concentrations of gases.
27. I. Knee OA
• The pathophysiology of OA
• Is complex and characterized by the softening and even destruction of articular
cartilage,
• with increased matrix degradation due to collagenases and proteoglycanases.
• The enzymes may be secreted by activated chondrocytes and monocytes, which by
releasing IL-1 and TNF-α amplify the in
fl
ammation.
• Synthesis of PGs increases several fold and there is a natural attempt to maintain a
biomechanical adequate matrix.
• In contrast to Rheumatic Arthritis, pannus does not develop.
• Joint pain may be aggravated by concomitant synovitis
28. I. Knee OA
Mechanism of Action
• Ozone dissolved in the water of synovial fluid, as usual, reacts with
biomolecules (antioxidants, PUFA, proteins) and generates Reactive Oxygen
Species (ROS) H2O2 and Lipid peroxidation product (LOPs) responsible for:
• (a) Possible inactivation and inhibition of the release of proteolytic enzymes,
proinflammatory cytokines, bradykinin and the synthesis of in
fl
ammatory PG,
with reabsorption of oedema and pain relief.
• (b) Stimulation of the proliferation of chondrocytes (probably via H2O2 ) and
fibroblasts, with increased synthesis of matrix and possibly of articular
cartilage.
29. I. Knee OA
Mechanism of Action
• (c) Neutralize proinflammatory cytokines such as IL-1, IL-8, IL-12, IL-15 and
TNF-alpha By an increased release of IL-1 soluble receptor or of other soluble
receptors
• (d) Conversely the release of immunosuppressive cytokines, such as
Transforming growth factor beta-1 (TGF-b1) and IL-10, may inhibit
in
fl
ammation.
30. I. Knee OA
• O2-O3 in osteoarticular diseases produces:
• a) better vascularisation on bones and cartilage,
accelerating anabolism and recovery;
• b) anti-in
fl
ammatory e
ff
ect by ozone activation over
PGs (prostaglandins);
• c) immunomodulatory e
ff
ect on autoimmune and
in
fl
ammatory diseases (such as Rheumatoid Arthritis
and Osteoarthritis);
• d) trophic e
ff
ects on bone and cartilage.
32. I. Knee OA
• Ozone therapy in patients with knee osteoarthritis has shown its e
ffi
cacy in
the short-term, when compared to placebo and when combined with
hyaluronic acid, even though no better outcomes were found when compared
to the current treatments (according to VAS).
• There are currently no convincing evidences in favour of a positive risk-bene
fi
t
ratio of ozone therapy in patients with knee osteoarthritis.
33. II. Ozone Nucleolysis
• It is a minimally invasive procedure done for prolapsed intervertebral disc
done by utilising the properties of a gas mixture of oxygen and ozone.
• It is injected into the prolapsed disc, causing reduction in the size of the
disc.
34. II. Ozone Nucleolysis
Mechanism of Action
• The following are the mechanisms by which ozone provides relief in low back
pain and radiculopathy:
• 1. Anti-in
fl
ammatory E
ff
ect:
• Ozone has an e
ff
ect on the in
fl
ammatory cascade by altering the breakdown
of arachidonic acid to in
fl
ammatory prostaglandins.
• As a result, in
fl
ammatory mediators are reduced.
35. II. Ozone Nucleolysis
Mechanism of Action
• 2. Herniation can impinge on the venous and arterial
fl
ow and cause
phlebostasis and arteriostenosis, which leads to a serious hypoxemia of
the area, thereby inducing in
fl
ammation.
• By applying the ozone to the herniated site, hyper-oxygenation of the area
occurs, which reduces the pain by direct and indirect mechanisms
36. II. Ozone Nucleolysis
Mechanism of Action
• 3. Ozone is a rapid and strong oxidizing agent.
• When ozone is injected into the disk, the active oxygen atom called the
singlet oxygen or the free radicle attaches with the proteoglycan bridges in
the jelly-like material or nucleus pulposus. They are broken down and no
longer capable of holding water.
• As a result, disk shrinks and mummi
fi
es, and there is decompression of nerve
roots. It is almost equivalent to surgical diskectomy and so the procedure is
called ozone diskectomy or ozonucleolysis
37. II. Ozone Nucleolysis
Mechanism of Action
• 4. The stimulation of
fi
broblastic activity by ozone will result in the initiation
of the repair process by stimulating collagen deposition.
• All these lead to decompression of nerve roots, decreased in
fl
ammation of
nerve roots, and increased oxygenation to the diseased tissue for repair work.
39. III. Prolozone Therapy
• Prolozone therapy is a technique which combines neural therapy,
prolotherapy, and ozone therapy.
• It involves injecting various combinations of local anesthetics, anti-
in
fl
ammatory medications, vitamins, minerals, proliferatives, and a mixture of
ozone-oxygen gas into degenerated or injured joints and pain generators
resulting in regeneration and reduction of pain.
40. III. Prolozone Therapy
Prolotherapy + Ozone
• Chronic pain and trauma in a patient results in decreased oxygen utilization.
• As oxygen utilization decreases, the ratio of NAD to NADH decreases.
• A decrease in ratio results in a slowdown of all cellular functions including
protein synthesis, cellular division, growth factor function, membrane
potential, etc.
• leading to an increase in free radical damage, which ultimately causes
in
fl
ammation and edema.
41. III. Prolozone Therapy
• Prolozone helps in re-establishing cellular membrane potentials, anti-
in
fl
ammation, providing substrates for oxygen utilization which is directly
stimulated by ozone.
• Ozone reacts with the double bonds in lipids and amino acids and creates
peroxides that are able to oxidize NADH to NAD, thereby correct the
declining NAD/NADH ratio.
• Thus, cellular function is stimulated and oxygen utilization is returned to
normal promoting healing
