done for launching of new product in pharma market

1. CONTENTS …
 COENZYME Q 10
 L- CARNITINE
 VITAMIN E AND TOCOTRIENOL
 ALPHA LIPOIC ACID
 VA

3. INTRODUCTION:
CoQ10 was first identified in 1940, and isolated from the
mitochondria of the beef heart, in 1957 by a biochemist
Frederick Crane.
 In 1958, its full chemical structure was reported by D. E.
Wolf and colleagues working under Karl Folkers at Merck.
In 1961 Peter Mitchell proposed electron transport chain
(which includes vital proton motive of coQ10) and received a
Noble Prize for it in 1978.

4. “A nutrient that the body needs in small amounts to function and stay
healthy. Coenzyme Q10 helps mitochondria (small structures in the
cell) that make energy.”
It is also called as Ubiquinone, Ubidecarenone vitamin Q10 and
abbreviated as CoQ10.
LETS MAKE IT MORE SIMPLE:
• Enzymes : Enzyme is a protein that act as catalyst to increase the
biochemical reaction rate without altering itself in the process.
• Co-enzymes : “Co-enzyme is an organic non-protein molecule that
is required by an enzyme to perform its catalytic activity.”
Co-enzymes are derived from vitamins. Hence it is also known as
vitamin Q-10.
• Where Q refers to Quinone (head) and 10 refers to number of
isoprene side chains repeated (tail).

6. • CoQ10 is a vitamin-like substance which is soluble in
lipids (fats) and present in eukaryotic cells, primarily in
the mitochondria. Expect RBC because it does not
contains nucleus nor mitochondria.
• It is the component of the electron transport chain and
participates in aerobic cellular respiration and helps to
generates the energy in the form of ATP.
• There are three redox states of coQ10: Ubiquinone
(oxidized form) Ubisemiquinone and ubiquinol (fully
reduced form)
Ninety-five percent of the human body’s energy is
generated this way.

7. MAJOR ORGANS REQUIRES COQ10

8. CAUSES OF COQ10 DECREASE
 Age dependant decrease.
 Use of statins.

9. LEVEL OF CO Q 10 FALL WITH AGE

10.  How it is synthesized?
It starts from acetyl-Co-A, a multistep process of
Mevalonate pathway produces farnesyl-pp (FPP) the
precursor for cholesterol and CoQ10.

12. FOOD SOURCES OF CO Q 10

13. MEDICINAL USAGE
 Powerful antioxidant
 Heart diseases
 Type 2 diabetes
 Migraine headaches
 Statin myopathy
 Dental disease (gum disease)
 Can be used as cosmecetuicals
 Osteoporosis: clinical study suggested that CoQ10
inhibits osteoclastogenesis and also promotes osteoblast
and matrix mineralization.

14. PHARMACOKINETICS OF COQ10
Absorption:
 Absorbed in small intestine into the lymphatic system
and then it enter in the blood.
 Can be highly variable depending upon the dosage form
and food intake.
 Absorption is lower if taken on an empty stomach and
higher when taken with food, especially those with a
high lipid content. Tmax is 8hrs.
distribution:
 It is distributed in blood and various lipoproteins: VLDL,
LDL and HDL.
 As it is found in all cells of the body and distributed to
various tissues of the body. (important to know that it is
able to enter in the brain)

15.  Takes around 3 weeks of daily dosage to reach the
maximum serum concentration level.
Metabolism:
 It is metabolized in all tissues by the process of
phosphorylation in the cells.
 Also assumed that metabolism and excretion of
exogenous CoQ is same as to endogenously
produced CoQ.
Excretion:
 Mainly through bile ( biliary tract)
 After oral administration over 60% of elimination is
through feces in unchanged form and some small
fraction of metabolites.
 Elimination Half-life is about 22hrs.

16. Drug interaction:
 Wafarin:
Blood thinning agent.
Simultaneous use of Warfarin and CoQ10 has been reported to
decreases the anticoagulant effect.
 Anthracyclines:
Anticancer drug but have cardiotoxic effect. Causes irreversible
damage to myocardial mitochondria.
This can be prevented by CoQ10 administration during cancer
chemotherapy without compromising their action.
 Statins:
This are HMG-coA reductase inhibitors
Used for controlling high cholestrol levels.
But due to same biosynthetic pathways, production of CoQ10 is
also affected.

18. WHAT IS L-CARNITINE?
 L-Carnitine is an amino acid (a building block for
proteins) which naturally produced in the body.
 carnitine was first extracted from meat extracts in 1905,
and its name is derived from Latin carnus or flesh.
 Carnitine is have 2 stereo isomers: its biological active
form is L-carnitine whereas its enantiomers D-carnitine,
is biologically inactive.
 D-carnitine is toxic and also inhibits the action of L-
carnitine.

19.  It plays critical role on energy production.
 In body, L-carnitine is formed in liver and kidneys from
amino acids lysine and methionine.
 The body makes sufficient carnitine to meet the needs
of most people.
 For genetic or medical reasons, some individuals
(such as preterm infants), cannot make enough, so
for them carnitine is a conditionally essential nutrient.
 Animal products like meat, fish, poultry, and milk are
the best sources. In general, the redder the meat, the
higher its carnitine content.

20. ROLE OF L-CARNITINE IN BODY
 L-Carnitine transports long chain fatty acids into
mitochondria so they can be oxidized (burned) to
produce energy.
 It also transports the toxic compounds generated
out of the cell organelle to prevent their
accumulation.
 Due to this key functionality L-carnitine is
concentrated tissues like skeletal and cardiac
muscle (heart) that uses fatty acids as a dietary
fuel.

21. DEFICIENCY OF L-CARNITINE:
 Two types of carnitine deficiency states exist:
 Primary carnitine deficiency:
a genetic disorder of the cellular carnitine-transporter
system that usually manifests itself by five years of age
with symptoms of cardiomyopathy, skeletal-muscle
weakness and hypoglycemia.
 Secondary carnitine deficiencies:
may occur due to certain disorders (such as chronic
renal failure) or under particular conditions (e.g., use of
certain antibiotics) that reduce carnitine absorption or
increase its excretion. There is scientific agreement on
carnitine’s value as a prescription product for treating
such deficiencies.

23. MEDICINAL USAGE OF L-CARNITINE
 Male Infertility
 Aging and bone loss
 Cardio vascular disease
 Type 2 diabetes
 Physical performance
 Obesity
 Also shown clinical results in neuropathic pain
management

24. PHARMACOKINETICS OF L-CARNITINE
 Supplementation of L-carnitine absorbed 5–18%
whereas 54–86% dietary L-carnitine is absorbed in the
small intestine and enters the bloodstream.
 The kidneys efficiently conserve carnitine, so even
carnitine-poor diets have little impact on the body’s
total carnitine content.
 Rather than being metabolized, excess carnitine is
excreted in the urine as needed via the kidneys to
maintain stable blood concentrations.

25. DRUG INTERACTIONS AND ADVERSE EFFECTS
 Anticonvulsant medications, including phenobarbital,
valproic acid, phenytoin, and carbamazepine, have a
significant lowering effect on carnitine levels.
 Carnitine interacts with pivalate-conjugated antibiotics
such as pivampicillin. Chronic administration of these
antibiotics increases the excretion of pivaloyl-carnitine,
which can lead to carnitine depletion.
 When taken in the amount of roughly 3 grams per day,
carnitine may cause nausea, vomiting, abdominal
cramps, diarrhea, and body odor smelling like fish. Other
possible adverse effects include skin rash, muscle
weakness, or seizures in people with epilepsy.

27. WHAT IS VITAMIN E?
 Vitamin E was discovered in 1922 by Herbert McLean
Evans and Katharine Bishop.
 Paul Karrer and his team first synthesized it in 1938.
 Vitamin E is a group of 8 fat soluble compounds that
include four tocopherols and four tocotrienols.
 Vitamin E= tocopherol+tocotrienol
Where,
 Tocos means “Birth”
 Pheros means “to carry”
 Ol means “ OH-group i.e. alcohol”
 An alcohol was capable to prevent reproductive failure in
animal.

28. CONTI…
 Vitamin E is a family of lipid-soluble compounds
consisting of two major groups i.e. Tocopherols and
Tocotrienols.
 Each group can be further divided into four different
isomers, that is alpha, beta, gamma, and delta.
 Depending on the presence and position of the
methyl group(s) as the side chain.
 Generally, vitamin E is made up of a chromanol ring
and an isoprenoid or phytyl side chain.
 to understand its difference lets see the strucutre:

30. CONTI…
 Tocopherols have a long and saturated side chain.
 While, Tocotrienols differ from Tocopherols by the
presence of unsaturated double bonds on the side
chain.
 This also explains the higher affinity of tocotrienols
to the lipid membrane compared to tocopherols.
 Vitamin E, particularly α-tocopherol, can easily be
obtained and consumed by the vast majority of the
world’s population.

31. FOOD SOURCES OF VITAMIN E
 Tocopherols rich foods:
It is found in various staple foods, such as
vegetable oils, palm oil, rice bran, wheat germ,
olive, barley, soybean, nuts and grains.
 Tocotrienols rich foods:
Are found in many different natural sources.
The percentages of tocotrienol content in
Rice bran (50%), palm oil (75%) and annatto
(99.9%) grape fruit seed oil, oats, hazelnuts,
maize, olive oil, Buckthorn berry, rye, flax seed oil,
poppy seed oil and sunflower oil.

32. FUNCTIONS OF VITAMIN E
 It is an antioxidant. This means it protects body
tissue from damage caused by substances called
free radicals. Free radicals can harm cells, tissues,
and organs. They are believed to play a role in
certain conditions related to aging.
 It helps keep the immune system strong against
viruses and bacteria.
 It helps to form red blood cells and widen blood
vessels to keep blood from clotting inside them.
 It helps the body use vitamin K.
 Cells also use vitamin E to interact with each other.
It helps them carry out many important functions.

33. HOW VITAMIN E ACTS AS ANTIOXIDANT
 Vitamin E is a potent chain-breaking antioxidant that
inhibits the production of reactive oxygen species
molecules when fat undergoes oxidation and during
the propagation of free radical reactions.
 It is primarily located in the all cell and organelle
membranes where it can exert its maximum
protective effect, even when its concentration ratio
may be only one molecule for every 2,000
phospholipid molecules.
 It acts as the first line of defence against lipid
peroxidation, protecting the cell membranes from
free radical attack.

34. CONTI…
 Due to its peroxyl radical-scavenging activity, it also
protects the polyunsaturated fatty acids present in
membrane phospholipids and in plasma
lipoproteins.
 It has been found that alpha-tocopherol mainly
inhibits the production of new free radicals, while
gamma-tocopherol traps and neutralises the
existing free radicals.

35. REACTION PROCESS

36. CONTI…
 Deficiencies of vitamin E are rare in humans.
 It is generally reported in people who have acquired
or inherited a type of condition that restricts their
ability to absorb this vitamin through diet or their
body inhibits fat metabolism.
 Its antioxidant activity linked to numerous possible
conditions/diseases including: ageing, cancer,
arthritis, neuronal problems and cataracts.
 Thus, vitamin E might help prevent or delay the
chronic diseases associated with reactive oxygen
species molecules.

37. PHARMACOKINETICS OF VITAMIN E
 The oral absorption of the vitamin E is done by
diffusion in the small intestine.
 Then it is transported by packing with chylomicrons
into the circulation via lymph nodes.
 Once vitamin E is packed into chylomicrons, it is
distributed either to body tissues or the liver.
 Vitamin E is then metabolized through the
hydroxylation and oxidation of its side chains by
cytochrome P450 to protect cells from damaging.
 Excretion is done through urine, bile and feces.

38. COMPARISON OF BOTH THE COMPOUNDS
TOCOTRIENOL TOCOPHEROL
(Tmax) = 3-4 Hrs post
meals
(Tmax) = 6 Hrs post
meals
(Cmax) = 0.89–1.92 µM (Cmax) = 1.82–2.92 µM
Elimination half-life (t1/2)=
2.3 to 4.4 Hrs
Elimination half-life (t1/2)=
20 Hrs

39. ADVERSE EFFECT AND TOXICITY
 Consuming higher dose of vitamin E (1000 mg/day)
for through supplements may lead to excessive:
 Bleeding
 Nausea
 Blurred vision
 Fatigue
 Bruising and
 Stomach cramps

40. DRUG INTERACTION
 vitamin E, when consumed from foods, do not
appear to cause any interactions with drugs.
 Supplementation of vitamin E may interact with
aspirin, Warfarin, Tamoxifen and cyclosporine A.
 For aspirin and Warfarin, high amounts of vitamin E
may potentiate anti-blood clotting action.
 One small trial demonstrated that vitamin E at
400 mg/day reduced blood concentration of the
anti-breast cancer drug Tamoxifen.
 In multiple clinical trials, vitamin E lowered blood
concentration of the immunosuppressant
medication, cyclosporine A.

41. MEDICINAL USAGE OF VITAMIN E
 Potent Antioxidant
 anti-inflammatory properties
 Protection of the Cell Membranes:
Helps to increases the orderliness of the membrane
lipid packaging, thus allowing for a tighter packing
of the membrane and, in turn, greater stability to the
cell.
 In Cardiovascular Disease
 In Cancer Treatment
 Cataracts
 Alzheimer’s Disease (AD)

42. CONTI…
 Skin protection
 Neuroprotection
 Anti-diabetic
 Anti-obesity
 Helps in bone and joints protection

43. TOCOTRIENOL: A NEW FACE OF
VITAMIN E UNFLODING
So, far, most humans supplementation studies have
used only tocopherols.
 Tocotrienols are mainly time found more potent as
anti-oxidants than tocopherols.
 But they are poorly assimilated by digestion and also
found poorly distributed to tissues in blood also are
rapidly metabolized and excreted by body.
 Tocotrienols, is beneficial in improving bone
strength by inducing bone formation and
osteoblast (bone-forming cells) activity, as well
as suppressing osteoclasts (cells mediating the
bone resorption process).

44. CONTI…
 It shows Neuroprotective action:
 Oral tocotrienol crosses the blood-brain barrier to reach
brain tissue; more so for fetal brain while pregnant
mother is supplemented with tocotrienol. Protects brain
against oxidative damage.
 α-Tocotrienol provided the most potent neuroprotection
among all vitamin E analogs. Reported effects of
tocotrienol independent of antioxidant property.
 Hypocholesterolemic:
 Three double bonds in the isoprenoid chain essential for
the inhibition of cholesterogenesis; tocopherols do not
share this property.

45. CONTI…
 Antioxidant:
 Tocotrienol have more potent action due to
unsaturated carbon chain (C=C)
 Have ability to locate closer to the cell membrane
surface.
 Retinopathy
 An eye disease which is caused due to the abnormal
flow of blood to the retina of the eye leading to
impaired vision.
 Age related Macular degeneration:
 a medical condition which may result in blurred or no
vision in the center of the visual field. Typically occurs
in older people.

47. INTRODUCTION
 Alpha-lipoic acid (ALA) also known as thioctic acid
(TA) and 1,2 dithiolane -3-pentanoic acid, is a naturally
occurring substance, that is essential for the function of
different enzymes in the body.
 ALA was discovered in 1937 by Snell but only in 1951 it
was isolated by Reed.
 ALA contains two sulfur atoms (at C6 and C8)
connected by a disulfide bond and it plays major role in
various enzymatic activity.
 Alpha lipoic acid can be eaten in foods, such as red
meat, carrots, beets, spinach, broccoli, and potatoes.
 A very small molecule works in both cell and also at
membrane level.

48. WHAT IS ALPHA LIPOIC ACID?
 Alpha lipoic acid is natural compound which works
as a co-factor in energy producing reactions.
 It is soluble in both water and fat.
 This allows it to work both inside the cell and at the
membrane level, that makes ALA a particularly
valuable antioxidant.
 It is also called as “Universal Antioxidant” because
it have effective action in water based substances
such as blood.
 While its reduced form Dihydrolipoic Acid (more
potent than LA) have in fatty tissues and
membranes.

49. STRUCUTURE OF ALPHA LIPOIC ACID

50. FUNCTION OF ALPHA LIPOIC ACID
 It serves as a coenzyme (i.e. facilitating the action
of enzymes)
 In general, antioxidants provide a preventive
measure against the hazards of oxidative stress
with their ability to neutralize, balance and sponge
up free radicals by coupling with unpaired
electrons.
 ALA is unique since it not only acts as antioxidant
against free radicals, but it also helps in the
regeneration process of expended antioxidants,
returning them to their reduced, antioxidant-potent
form.
 In short, it helps to recycle other antioxidants.

51. CONTI…
 ALA is a key ingredient in providing the maximum
interaction among antioxidants, enhancing their cell
protection abilities.
 It also has unique ability that enhances the power
of vitamin E, C and Glutathione.
 Alpha-lipoic acid is essential for metabolizing
carbohydrates, proteins, and fats and for the
conversion of their energy into ATP.
 It also have ability to cross blood brain barrier that
helps to increase brains energy availability.

52. PHARMACOKINETICS
 The absorption and bioavailability of ALA have been
studied mainly dietary supplements where ALA exists as
an admixture of R-ALA and S-ALA. In general, the
absolute bioavailability of both enantiomers is not
greater than 40% which decreases with food intake.
 Therefore, ALA must be taken 30 min before meals.
 Absorption is done in intestine then transported to
various organs such as brain (as it can freely pass
BBB), liver, hear and other body tissues for metabolism.
 Excreted through urine.
 Plasma half life is 30 minutes.(too short)

53. SIDE EFFECTS
 The most common side effects of supplementation
with oral lipoic acid were allergic reactions of the
skin, such as rashes, itching and hives.
 Nausea, vomiting, abdominal pain, diarrhea and
vertigo were also occasionally reported.

54. MEDICINAL USAGE
 Diabetes: ALA has been used to control blood
sugar and in prevention and treatment of diabetic
complications including retinopathy, neuropathy and
renal diseases.
It has potential preventive or ameliorative effects in
both type I and type II diabetes.
In patients with type 2 diabetes, lipoic acid
supplementation has been shown to improve insulin-
sensitivity.

55. CONTI…
 Cardiovascular disease: It is now generally
accepted that oxidized LDL (low density
lipoproteins) is a risk factor for atherosclerosis( a
disease of the arteries characterized by the
deposition of fatty material on their inner walls.)
It protects LDL and also apolprotein of coronary artrial
wall from oxidative damage.
 Ischemic-perfusion injury: This injury occurs
when a burst of free radicals is produced during re-
oxygenation of tissue that has become hypoxic like
in cardiac tissue and brain.
ALA/DHLA has shown to be effective in preventing
this damage.

56.  Neurological Diseases: ALA helps in slowing
progression of Alzheimer's disease and dementia. It
has shown to improve memory in older individuals.
It has also shown its effect on Parkinson’s disease,
stroke and spinal cord injuries.
 Neuropathy: Free radicals are hypothesized to
play a role in neuropathy, and, on this basis, lipoic
acid has been tried as a treatment. There is well
known evidence for oral lipoic acid in treatment of
peripheral and autonomic neuropathy especially in
diabetes.

57.  obesity: ALA has recently been shown to exert
potent anti-obesity effects by suppressing
hypothalamic AMP-activated protein kinase activity.
 Osteoporosis: current data indicate that alpha-
lipoic acid protects from bone loss via a 2-
pronged mechanism involving inhibition of
osteoclastogenic reactive oxygen species
generation and up-regulation of redox gene
expression.

58.  Alpha lipoic acid is an important and
multifunctional antioxidant that destroys many of
the free radicals that are harmful to the human body
and is rightly been described as described as
“universal”, “ideal”, “broad spectrum” and
“metabolic” antioxidant.
 Several studies are been undertaken to show
efficacy of ALA in general and oral diseases.
 Its more number of benefits makes it a reliable
modality in fields of medicine and dentistry.

59. VISUAL AID
CARNIMENT- Q10
TABLET
THE PROTECTING SHIELD

60. CARNIMENT-Q10 TABLET
 each tablet contains: Coenzyme Q10 50mg + L-
Carnitine 500mg + Tocotrienol 60mg + Alpha lipoic
acid 50mg + Vitamin E 15IU
 INDICATED FOR:
 OXIDATIVE STRESS
 CV DISORDERS
 DIABETES
 NEUROPATHIC PAIN
 CONDITIONS IN ELDERLY PATIENTS