KANEKA Q10 - Quetzal Quimica

KANEKA Q10
Functional Food Ingredients Division
KANEKA CORPORATION
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Edition 01

KANEKA Q10 Product Line
KANEKA Q10 SE2.5
KANEKA Q10 EP40
KANEKA Q10 (bulk)
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Edition 01

Contents
(1) Technologies of Kaneka (Fermentation)
(2) Physical/Chemical Properties (What is Coenzyme Q10?)
(Description)
(Stability)
(3) Production Method (Fermented-yeast extract)
(Chemical synthesis)
(Trans- and Cis-isomers)
(4) Key Features (Concept of KANEKA Q10)
(Safety)
(Safety: 52-Week oral gavage chronic toxicity in rats)
(Reliability)
(High Quality)
(High Quality: KANEKA Q10 EP40)
(High Quality: KANEKA Q10 SE2.5)
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(1) Technologies of Kaneka (Fermentation)
Modifiers (resin modifiers)
PVC resins
Reactive polymers
ABS Resins
Acrylic synthetic fibers
Expanded cushioning materials
Plasmapheresis system
Pharmaceutical
products
New biotechnology
KANEKA Q10
Caustic soda
Baker’s yeast
Molecular design technologies
Macromolecular technologies
Fermentation
technologies
Insulating construction materials
Polymer processing technologies
Electronic
materials
Inorganic material technologies
Super-heat resistant
polyimide films
Foodstuffs
Amorphous material
technologies
Solar battery
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(2) Physical Properties (What is Coenzyme Q10?)
Common name: Coenzyme Q10 (CoQ10, Ubiquinone)
- Chemical Name: 2,3-Dimethoxy-5-methyl-6-
decaprenyl-1, 4- benzoquinone
- CAS registry number: No. 303-98-0
- Molecular Weight: 863.36
C 59 H 90 0 4
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(2)Physical/Chemical Properties (Description)
Physical and chemical characteristics
- Appearance: Yellow to orange crystalline
powder
- Solubility:
- Water: Insoluble
- Ethanol: Practically insoluble
- Diethyl ether: Freely soluble
- Melting point: About 48ºC
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(2) Physical/Chemical Properties (Stability)
Precautions about the quality and properties of
Kaneka Q10
- Store in a sealed container protected from
light, as the product is unstable when
irradiated.
- Processing at high temperature may cause
decomposition.
- Store at a temperature of 25ºC or lower.
- Contact with alkali may make the product
unstable.
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(3) Production Method (Fermented-yeast extract)
Yeast containing Coenzyme Q10
Extraction
Purification
Crystallization
Drying
Purified Coenzyme Q10
KANEKA Q10 (final product)
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(3) Production Method (Chemical synthesis)
Other production methods of Coenzyme Q10
(excluding fermented-yeast extract)
- In addition to Kaneka's
yeast fermentation
method, there are many
other chemical processes
practiced for production
of Coenzyme Q10.
(Side chain part)
Tobacco
Solanesol
CH3
HO-(-CH2CH=CCH2-)9-H
Decaprenylbromide
(Quinon part)
Tri-methoxy
toluene
CH3
CH3O
OCH3
OCH3
DMBQ
DMHQ
- An example of such
chemical methods, which
is estimated from patent
literature, is shown here.
Coupling
Crude CoenzymeQ 10
Product
Impurities
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(3) Production Method (Trans- and Cis-isomers)
• Trans-isomer
(Natural CoQ 10 )
H 3 CO
H 3 CO
O
CH 3 CH 3 CH 3
CH 3
8
CH 3
O
• Cis-isomer
(Impurity of Synthetic
CoQ 10 )
H 3 CO
O
CH 3 CH 3
CH 3
CH 3
8
H 3 CO
O
CH 3
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(4) Key Features (Concept of KANEKA Q10)
Safety, Reliability, and High Quality
Kaneka Q10 is an yeast extract, naturally occurring substance.
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(4) Key Features (Safety)
Safety
- Kaneka Q10 is yeast-derived Coenzyme Q10
with an all-trans configuration, which is
identical with naturally-occurring Coenzyme
Q10 contained for example in meat, fish and
others.
- The safety of KANEKA Q10 is assured in
various safety tests including a 52-week oral
gavage chronic toxicity study in rats conducted
by one of the world's highest-level testing
laboratories (Covance Laboratories Inc.).
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(4) Key Features (Safety)
Test Item
Toxicity Study
4-Week oral gavage toxicity in rats
52-Week oral gavage chronic toxicity in rats (J. Agri.
Food Chem. 47:3756-3763, 1999)
Mutagenicity (Genotoxicity) study
Bacterial reverse mutation test
Chromosomal aberration test
Micronucleus test in mice
Test Results
Lethality dose for CoQ10 was >5,000 mg/kg for a single oral dose in male
and female rats
CoQ10 was given orally at a dose of 300, 600, or 1200 mg/kg/day daily for 4
weeks. There were no CoQ10-related signs in clinical symptom,
hematology, blood chemistry, urinalysis, and pathology. The tolerated
dose was 1200 mg/kg/day.
CoQ10 was given orally daily for 52 weeks at a dose of 300, 600, or 1200
mg/kg/day. There were no CoQ10-related signs in clinical symptom,
hematology, blood chemistry, urinalysis, and pathology. The tolerated dose
was 1200 mg/kg/day.
CoQ10 showed no mutagenic activity in an assay with 4 strains of
Salmonella typhimurium and E. coli WP2 uvrA (Ames test). (Negative
mutagenicity)
CoQ10 had showed no chromosomal aberration in an assay with Chinese
hamster pneumocyte (CHL/IL). (Negative mutagenicity)
CoQ10 had no clastogenic activity or adverse action in the bone marrow
cells of CD-1 (ICR) mice. (Negative mutagenicity)
Others: No significant toxicity of CoQ10 was observed in the test of primary skin irritation in
rabbits, 2-week cumulative skin irritation in rabbits, eye irritation in rabbits, acute dermal
photoirritation in guinea pigs, contact photosensitization in guinea pigs, or allergic toxicity
(skin-sensitization in guinea pigs).
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(4) Key Features (Safety: 52-week Oral Gavage
Chronic Toxicity Study)
52-week Oral Gavage Chronic Toxicity Study
with Ubiquinone in Rats with a 4-week Recovery
(Covance Laboratories Inc.)
Potential "KANEKA Q10" toxicity to rats was
assessed in a 52-week gavage chronic test, by
orally administering KANEKA Q10 at a dose of
100, 300, 600, or 1,200 mg/kg-day.
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Edition 01

(4) Key Features (Safety: 52-week Oral Gavage
Chronic Toxicity Study)
52-week Oral Gavage Chronic Toxicity Study
with Ubiquinone in Rats with a 4-week
Recovery (Covance Laboratories Inc.)
Material: KANEKA Q10 / Corn oil
Animals: 247 male and 247 female rats (total of 494 rats)
Dose: 100, 300, 600, or 1,200 mg/kg-day
Administration: once a day, forced oral administration
Test items:
- Morbidity/Body weight/Food consumption
- Hematology and blood biochemistry
- Urine chemistry/Ophthalmic examinations
- Histopathology etc.
- Toxicokinetic analysis (blood CoQ10 concentration)
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Edition 01

(4) Key Features (Safety: 52-week Oral Gavage
Chronic Toxicity Study)
52-week Oral Gavage Chronic Toxicity Study
with Ubiquinone in Rats with a 4-week
Recovery (Covance Laboratories Inc.)
KANEKA Q10 was well tolerated by male and
female rats at a dose level of up to 1,200 mg/kg-day.
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Edition 01

(4) Key Features (Reliability)
Reliability:
- KANEKA has been supplying Q10 over 25 years
domestic and abroad as the leading manufacture.
- Production strictly complying with GMP
- Greater academic supports provided, based on the
Kanaka’s close network with leading researchers in the
world.
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(4) Key Features (Reliability)
Pharmaceutical
Manufacturer License
GMP Certificate
KOSHER Certificate
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(4) Key Features (Reliability)
International Coenzyme Q10 Association
• Established: September 1997
• Object: Promotion of academic exchange among
researchers who are involved in coenzyme
Q10 studies.
Improvement of the public recognition of
Coenzyme Q10
• Chairman: Prof. G.P. Littarru (Universita di Ancona, Italy)
• KANEKA is a founding member supporting the Association.
• Past conferences (held biannually):
1st Conference: Boston in 1998
2nd Conference: Frankfurt in 2000
3rd Conference: London in Nov 2002
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(4) Key Features (Reliability)
www.coenzymeQ10.org
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(4) Key Features (Reliability)
Japanese Coenzyme Q Association
• Established: November 2002
• Object: Promotion of academic exchange among
researchers who are involved in coenzyme Q10
studies.
Improvement of the public recognition of
Coenzyme Q10
• Chairman: Prof. J. Yamamoto (Tokyo University of
Technology, Japan)
• KANEKA is a founding member supporting the Association.
• 1st Conference: Tokyo on Feb. 28, 2003
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Edition 01

(4) Key Features (Reliability)
www.coenzymeQ-jp.com
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(4) Key Features (High Quality)
High Quality
- Kaneka provides the highest-quality Coenzyme Q10,
which is produced based on the proprietary
manufacturing technology and quality management
system that are rated as one of the most advanced in the
world.
- Kaneka is now developing new high-quality products
satisfying the specific needs of the customers, such as
emulsifiable powders and water-soluble superemulsifiable
powders.
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Edition 01

(4) Key Features (High Quality)
Panoramic view of the Takasago Plant
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(4) Key Features (High Quality)
Quality-control test equipment
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(4) Key Features (High Quality: KANEKA Q10
EP40)
KANEKA Q10 EP40 (40% Emulsion Powder)
EP 40
Existing product
●Fermentation product with an all-trans structure
(containing no Cis-isomers)
●Microcapsulated powder product allowing
emulsions with a high concentration of up to 40%.
● Excellent solubility, soluble even in cold water
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(4) Key Features (High Quality: KANEKA Q10
SE2.5)
KANEKA Q10 SE2.5
● Fermentation product with an all-trans structure
(containing no Cis-isomers)
● Allows emulsification at the nano-order
by super-emulsification technique
● Extremely favorable emulsion stability even in
the presence of other materials
● Excellent storage stability, generating no oil rings
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