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What is Ascorbyl Glucoside?
It is a new type of
stable Vitamin C that is not oxidized, but still shares the same
physiological activation mechanism as ordinary Vitamin C (Chemical
name: Ascorbic acid). By formulating the product with Ascorbyl
Glucoside, the less degradable Vitamin C exerts a sustained action
on the skin, bringing about remarkable effects not only in improving
discoloration and freckles, but also in stimulating collagen
production to prevent the ageing of skin.
Vitamin
C is an excellent lightening agent. Preventing the activation of
tyrosinase, it blocks the excess melanin formation, the pigment
responsible for discoloration and freckles. It also lightens the
discoloration and freckles already formed.
Vitamin C - so unstable,highly degradable
Ordinary Vitamin C used to be degraded so easily that it was very
difficult to make it work effectively inside the skin.
It is a
new type of stable Vitamin C that is not oxidized, but still shares
the same physiological activation mechanism as ordinary Vitamin C
(Chemical name: Ascorbic acid). By formulating the product with
Ascorbyl Glucoside, the less degradable VITAMIN C exerts a sustained
action on the skin, bringing about remarkable effects not only in
improving discoloration and freckles, but also in stimulating
collagen production to prevent the ageing of skin.
The high
compounding ratio of ascorbyl glucoside is the secret behind the
great lightening effects of 1/f ID white range
All
products in the 1/f ID white range contain a remarkably high
concentration of Ascorbyl Glucoside. By using the skincare items one
over the other, the lightening effect also becomes enhanced. The 1/f
ID white range sets out at once to restore skin to its natural,
original, newly born condition.
Aggregation of Vitamin C derivatives in water solution:
The
basic molecular architecture of amphiphiles is always based on the
simultaneous presence in the same molecule of two or more groups of
atoms that possess different affinities for a solvent, with which
they establish different interactions, and that is generally defined
as a "selective solvent". Usually the solvent is water, and then we
distinguish a hydrophilic part (the "polar headgroups"), linked to a
hydrophobic block made up of one, two, or more hydrocarbon chains
(see Fig. 5).
The polar headgroups
can be either neutral, cationic, or anionic residues. Typical
neutral surfactants contain functionalities such as -OH, -NR2
(R=alkyl or H), esters, ethers, amides, and so forth. Cationic
amphiphiles are for example alkyl-ammonium salts (such as
dioctadecyldimethylammonium chloride, usually called DODAC), while
anionic tensides can be carboxylates, sulfates, or phosphates. On
the other hand, phosphatidylcholines are typical zwitterionic
amphiphiles.
An interesting class
of molecules are the so-called bolaamphiphiles, where two
headgroups are bound by one or two chains (see Fig. 5). In this case
monolayered structures are formed. These surfactants are typically
present in the membranes of Archaebacteria, primordial
microorganisms that live in extreme environments, such as volcanoes
or under the oceans, and experience very drastic environmental
conditions (pH<2, T>70° C, and high pressures).
Amphiphiles promptly
form supramolecular aggregates in water, because of the "hydrophobic
effect", that is the formation of a hydrophobic central core and of
an external hydrophilic shell. This process reduces the
hydrocarbon-water repulsion and then minimizes the total energy of
the aggregate.
Depending on the
chemical structure of the amphiphile, temperature, ionic strenght of
the solution, nature and composition of the solvent, different kinds
of aggregates can be obtained, with peculiar properties and
structures. As Fig. 5 shows, spreading monolayers, adsorption films,
micelles, vesicles (or liposomes), microemulsions, and Langmuir-Blodgett
multilayers are different supramolecular structures, but they all
originate from the same self-assembly of surfactants in the presence
of a selective solvent.
Fig. 5 -
Schematic structure of amphiphiles and of their self-assembled
supramolecular aggregates.
Although
the driving force that leads to the formation of these structures is
always the "hydrophobic effect", however each one of the
supramolecular assemblies possesses peculiar properties that can be
studied with different techniques. Just as an example, monomolecular
films are basically studied by measuring the "spreading isotherms",
that is the plot that one can obtain by measuring the surface
pressure as a function of the surface area; micellar solutions can
be regarded as dispersions of small particles (usually spheres or
ellipsoids) that can be characterized by surface tension
measurements, refractive index, light-scattering,
neutron-scattering, viscosity, EPR, NMR, and so forth. Emulsions and
microemulsions are of great interest when an intimate mixture of
lipophilic and hydrophilic components is desidered, such as in
drugs, cosmetics, food processing, paper and textile manufacturing,
oil recovery, inks and paintings, and so forth, and for this reason
the study of their stability and phase behavior as a function of
temperature and composition, i.e. the "phase diagram", is strongly
needed.
Fig. 6 shows the
spreading isotherms obtained from 6-O-stearoyl ascorbic acid at
pH=6, vitamin K1, and vitamin D3 at 25°C. As
expected, 6-O-stearoyl-ascorbic acid produces more condensed films,
because of its long aliphatic side chain, whilst the other two
components give monolayers that show a more expanded behavior. The
spreading behavior of ascorbyl-palmitate has been studied by
Balthasar and Cadenhead.
Fig.
6 -
Spreading isotherms (surface pressure vs. molecular area) of
ascorbyl-stearate, vitamin K1, and vitamin D3.
The formation of
self-assembled aggregates in water strongly depends on several
factors: surfactant concentration, temperature, ionic strenght,
presence of other molecules. When a surfactant is progressively
added to water, it will dissolve in the bulk and form an adsorption
film at the air/water interface; adding more surfactant will result
in the formation of the first aggregates when the concentration
equals the "critical micellar concentration", CMC (see Fig.
7).
Fig. 7
- Formation of
supramolecular aggregates in a multi-component equilibrium with the
surfactant's monomers. The blue spots represent the polar headgroups,
and the brown lines indicates the hydrophobic chains.
For c<CMC, the single
monomers float in the bulk phase, and begin to produce the so-called
adsorption film at the air/water interface, where they orient the
hydrophobic chains out in the air, while the polar headgroups are
anchored in the aqueous phase. For c>CMC, the monomers'
concentration remains equal to the CMC, but the number of aggregates
increases (see Fig. 7). In spite of this "static" model, it should
be remembered that a micellar system is instead very dynamic, in
fact the monomers diffuse all the time from one aggregate to the
other, spending some time in the bulk solution as single molecules.
The CMC can be easily determined as the crossing point of the two
straight lines obtained from the least square fitting of the surface
tension vs log c data, as Fig. 8 shows in the case of
6-O-stearoyl-ascorbate water solutions at T=30°C and pH=6. CMC can
also be measured by other techniques, such as light-scattering,
viscosity, conductivity, density, and is generally obtained as the
point where the macroscopic parameter suddenly changes, due to the
formation of micelles, ultimately of an oil core surrounded by a
hydrophilic shell.
Fig. 8 - Calculation
of the CMC value from the surface tension vs. concentration plot.
The red spots are the experimental data, the black lines are the
fitting linear curves. CMC is determined as the intersection point
of the two lines.
From this plot it is
easy to calculate the area per polar headgroup, A; for a nonionic
surfactant the following Gibbs' equation holds:
where R=8.31·107
erg/mol·K, T is the absolute temperature, and NA is the
Avogadro number. For the previous plot, A was calculated as 47 Å2/molecule.
When the surfactant is charged, A must be multiplied by a factor 2.
The CMC value is
affected by several factors, first of all by the chamical structure
of the tenside (hydrophilic/hydrophobic balance, charges, branching
groups, unsaturated bonds), by the temperature and by the presence
of other molecules and/or ionic species.
The shape and the size
of the supramolecular structures - that is the number of monomers
per aggregate ("aggregation number", g) - depend on the chemical
nature and geometry of the surfactant, on the monomers'
concentration and on the temperature.
More recently the
formation of large interface aggregates in non-aqueous solvents and
with different types of chains has been reported in several papers,
provided that the selective solvent plays different interactions
with the two incompatible building blocks of the solute. As an
example, a semifluorinated n-alkane, bearing a hydrogenated segment
linked to a fluorinated block, can form aggregates in a fluorocarbon
such as perfluorooctane, because of the well-known mutual
immiscibility of hydrocarbons and fluorocarbons.
The self-assembling of
surfactants in water and related properties are well described in
several books .
As already mentioned
in the previous section, a large number of lipophilic derivatives of
vitamin C can be synthesized, where the polar head group is the
ascorbic acid moiety, linked to one or two hydrophobic chains.
Assembled in such supramolecular structures, vitamin C derivatives
protect degradable materials (particularly unsaturated fats or
vitamins): in fact the lipophilic molecules are segregated and
protected in the micellar hydrophobic core, whilst the ascorbic acid
polar head groups face the water phase and perform their
radical-scavenger activity. As a matter of fact, when the vitamin
C-based surfactants aggregates in micellar structures, the active
ascorbic ring is even more exposed to the facing aqueous medium.
Long chain derivatives of ascorbic acid readily produce
monomolecular films at the air/water interface, and give stable
mixed monolayers with some vitamins that possess an amphiphilic
structure as well. This feature is particularly important in order
to determine the mutual miscibility of ascorbic acid derivatives and
some relevant natural compounds with a perspective of producing
stabilized systems where the ascorbyl-derivatives protect the other
components against oxidation.
The self-assembly properties of 6-O-octanoyl ascorbic acid in water
have been recently studied with viscosity, light-scattering and
small-angle neutron-scattering measurements. The data show that
small, monodisperse, nearly spherical aggregates are formed, with a
hydrodynamic radius of about 25 Å. The oxygen consumption and the
reducing activity of this compound have been tested and show that it
is at least as powerful as vitamin C.
The structure and
properties of another derivative, namely the 5,6-octylidene-ascorbic
acid, are currently being studied in aqueous beta-octyl-glucoside
micelles.
6-O-ascorbic acid
esters, such as palmitate, are almost insoluble in water at room
temperature, however their solubility increases at higher
temperature, above which a clear solution is formed. This is due to
the formation of micelles from the saturated solution of monomers,
and therefore is referred to as the critical micellization
temperature, CMT. Upon cooling, the micellar solution solidifies
into an opaque curd, that contains more than 80% of water, and is a
semicrystalline mesophase, usually called "coagel".
Fig. 9 - Synergic
interplay of ascorbic acid, carotenoids and tocopherols in the
protection of lipid fats against oxidation.
However,
it is important to recall that what has been observed in vitro, may
not be automatically transferred to the living systems, as a matter
of fact Walther et al. showed that the addition of vitamin E to
antioxidant liposomes delivered to fetal lungs significantly reduced
the surface activity, and then it may not represent a suitable
approach to perform radical scavenging in vivo.
Moreover, the current
increasing amount of radical species that are present in the
atmosphere (particularly nitrogen oxides), the seasonal partial loss
of the ozone layer, and then the increase of the ultraviolet
irradiation over the Earth, are all related problems that show the
importance of using antioxidant species in protecting the body from
the free radicals' attacks, or in minimizing their dangerous
activity. On the other hand we must be aware that the fashionable
habit of large intakes of ascorbic acid and its derivatives on a
regular basis may represent a serious hazard to the human health,
for the possible consequences of producing radicals directly into
the body, for instance through the reaction with metal ions such as
iron and copper.
A huge list of patents
already reports several preparations, based on ascorbic acid or on
its organic derivatives. Many academic and industrial Laboratories
have studied the properties of lotions, creams, drugs, and cosmetic
products with the aim of improving the antioxidant protecting
activity of tocopherols by adding ascorbic acid or its derivatives,
and of widening their applications and uses. Some of these systems
require the use of both aqueous and hydrophobic phases, emulsionated
with a proper amount of surfactants. Other compounds, like
3-alkyl-ascorbic acids, have been tested as antioxidants and found
to be very strong chain-breaking agents with a high affinity for
biomembranes, suggesting that some lipophilic derivatives of
ascorbic acid could be of benefit for protection against reperfusion
injury. Moreover, 3-O-alkyl-ascorbic acids were found to be stable
in ointments and to suppress intracellular melanin accumulation in
the skin. The effect of 3-alkyl-ascorbic acids has been reported by
Nihro et al..
Other studies indicate
that 6-O-ascorbyl-alkanoates are much more active in preventing
oxidation of linoleic acid than ascorbic acid in SDS, Triton, and
CTAB micelles, despite the fact that ascorbic acid-palmitate and
ascorbic acid show a similar efficiency in homogeneous solutions. In
the case of a lipophilic derivative of ascorbic acid such as
ascorbic acid-palmitate, the electrostatic interactions with the
polar headgroups of the surfactants (the cationic CTAB or the
anionic SDS) are no longer relevant for its antioxidant properties.
Another interesting difference between ascorbic acid and its
lipophilic derivatives is that in the case of vitamin C the maximum
rate is reached for SDS or CTAB concentrations above the CMC, whilst
in the case of ascorbic acid-palmitate the rate decreases with
increasing surfactant concentration. This may be due to the inter-micellar
diffusion dynamics that contributes to the rate-limiting step. The
same finding was obtained studying vitamin E in SDS micelles. These
results demonstrate that the inter-micellar diffusion is one of the
main factors that affect the antioxidant activity and does depend on
the lenght of the hydrophobic chain.
The antioxidant
synergism of vitamin E and vitamin C has been recognized and
extensively studied. The key step is the reaction between the
tocopheroxyl radical (TOC·) and vitamin C (ASC):
TOC·
+ ASC- = TOC + ASC·
[ 1 ]
introducing a
lipophilic chain in position 5 or 6 in vitamin C does not change its
reactivty toward TOC· in homogeneous solutions, but the
rate constant for reaction [1] is lowered by a factor 10 in the
presence of phosphatidylcholine liposomes. In this case the
lipophilic vitamin C derivative may either reside in the same or in
a different micellar structure than that where the TOC·
radical is, in the latter case therefore it must diffuse out from
its micelle before reacting with TOC·, and then the total
rate constant would depend on the lenght of the side chain. The most
interesting insight is that a liposome fusion mechanism must be
invoked to rationalize the antioxidant activity in vesicles.
Liposomes are dynamically stable systems below the transition
temperature due to the tremendous hydration repulsion force against
the get-together of two liposomes.
However, fusion could
be induced by some ionophores or fusogens, such as Ca2+
which may form a bridge between two liposomes facilitating the
fusion. The incorporation of ascorbic acid-derivatives into lecithin
liposomes would make the liposomal surface negatively charged. Of
course attractive electrostatic interactions between oppositely
charged liposomes would serve as a driving force to induce the
fusion. The intraliposomal diffusion may also contribute, because
subsequent to the liposome fusion the two substrates must subject to
fast lateral intraliposomal diffusion to find each other for the
reaction to occur.
Preliminary biological
assays have been performed to check if the same findings occur in
the case of biomembranes. The antioxidant activities of octanoyl-
and palmitoyl-ascorbic acid are much better than that of ascorbic
acid and tocopherol, both in vivo and in vitro. An interesting
observation is the delicate balance played by the lenght of the side
hydrophobic chain, in fact longer alkyl segments facilitate the
insertion of the ascorbic acid derivative into the bilayer, but they
also make the interfacial diffusion more difficult. Lauroyl-ascorbic
acid seems to be the best agent in that sense.
Similar conclusions
were drawn by Liu et al. in their study on the antioxidant
activities of ascorbic acid and ascorbyl-palmitate, carrying out ESR
measurements on bilayered vesicles made up of an anionic surfactant
(SPHS = 1-pentadecyl hexadecyl sulphate) and a stable lipophilic
nitroxide probe (TEMPO-16). The results indicate the occurrence, in
the case of ascorbic acid, of a two-step reaction that first
involves the external vesicle surface that interacts with vitamin C
dissolved in the aqueous bulk phase, and only in a second time the
TEMPO molecules that are confined in the inner layer will enter into
the aqueous medium after a flip-flop diffusion motion across the
membrane. On the other hand, when palmitoyl-ascorbic acid is
directly incorporated into the SPHS vesicles a much fast reaction
occurs, that can be explained, again, with a vesicle fusion
mechanism.
The radical attack operated by an initiator usually follows the
following general path:
As radical initiator
the following molecules are mostly used, depending on the medium
where the reaction is going to be taken: DPPH (alpha,alpha-diphenyl-beta-picrylhydrazyl),
water soluble; AMVN
(2,2'-azobis(2,4-dimethyl-valeronitrile)), oil soluble; AAPH
(2,2'-azobis(2-amidinopropane)dihydrochloride), water soluble;
AIBN (2,2'-azobisisobutyronitrile), oil soluble; DBHP (di-tert-butyl
hyponitrite), water soluble.
Fig. 10 shows that
ascorbic acid esters incorporated into phospholipid vesicles (liposomes)
significantly suppress the oxidation of the unsaturated components,
and produce an induction period, after which the peroxidation
proceeds with the same slope as in the absence of the radical
scavenger.
The next plot (Fig. 11)
shows the time dependence of absorbance when a solution of linoleic
acid is first treated with some radical initiator (AIBN or DPPH,
depending on the solvent medium), and then with some radical
scavenger. The curve indicates that as soon as the radical promoter
is added, the unsaturated fatty acid is attacked and forms the
conjugated diene that absorbs at 234 nm. The radical scavenger
momentarily stops the peroxidation of linoleic acid until it is
completely consumed as the second plateau indicates, and then the
oxidation starts again with the same kinetic as before.
Fig.
11
- The oxidation process of linoleic acid can be monitored by
measuring the absorbance at 234 nm as a function of time. The arrows
indicate the addition of the radical initiator and of the radical
scavenger to the solution.
The antioxidant
activity of different natural and synthetic chemicals is a very
important property, especially for industrial applications. A simple
method to evaluate such parameter consists in measuring the
absorbance before and after the addition of each antioxidant to an
ethanolic solution of a proper radical initiator, such as DPPH (see
structure below). This radical promoter is deeply colored (purple)
and absorbs at 517 nm. The addition of an antioxidant agent
determines the fading of its color, and the rate is related to the
efficiency of the radical scavenging. The reducing activity (RA, %)
can be easily derived from the following equation:
where A(0) and A(20)
are the absorbance values (at 517 nm) before adding the reducing
agent and 20 minutes after its addition, respectively. Some products
have been tested according to this procedure, and the results are
shown in Fig. 12.
Asorbyl
Glucoside:
this form is largely used by Japanese cosmetics companies for
whitening and brightening purposes. It works best in a synergy with
other skin-lighteners like kojic acid, bearberry extract, mulberry
extract, etc. It helps prevent abnormal melanin formation and
retention. |
