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A Stable Liposomal Composition Comprising Ascorbic Acid

Abstract: A topical delivery system comprising liposome encapsulating ascorbic acid wherein the liposome is formed from surfactants (e.g. phospholipids, cationic surfactants, anionic surfactants), sterols such as cholesterol, fatty acids and/ or hydrophobically modified surfaceactive polymers. The stable liposomal composition of ascorbic acid comprising, 0.01% to about 20% by weight aqueous solution of ascorbic acid wherein said ascorbic acid is pure and stable up to pH 7.0. A process for preparing the liposomal composition of ascorbic acid comprising (a) dissolving sterol, surface-active polymers, fatty acids in ethanol, (b) ascorbic acid solution in cooled boiled water, (c) adding the ascorbic acid solution obtained from step (b) to the mixture obtained from step (a) drop by drop under constant stirring condition, (d) mixing solution comprising surfactant and surface-active polymer and adding to the above mixture obtained from . step (c) under constant stirring and (e) adjusting pH of the solution to 6 to 7 using alkali.

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Patent Information

Application #
Filing Date
11 February 2010
Publication Number
37/2016
Publication Type
INA
Invention Field
Status
Email
Parent Application
Patent Number
Legal Status
Grant Date
2017-08-01
Renewal Date

Applicants

ITC LIMITED
37, J.L. NEHRU ROAD, KOLKATA - 700 071, STATE OF WEST BENGAL, INDIA

Inventors

1. BISWAS, SAMARES, CHANDRA
ITC R&D CENTRE, PENNYA INDUSTRIAL AREA, PHASE 1, BANGALORE 560058, INDIA
2. MURUGESAN KAVITHA
ITC R&D CENTRE, PENNYA INDUSTRIAL AREA, PHASE 1, BANGALORE 560058, INDIA
3. CHOWDHURY BROJOKISHORE
ITC R&D CENTRE, PEENYA INDUSTRIAL AREA, PHASE 1, BANGALORE 560058, INDIA
4. ROY DHIMOY
ITC R&D CENTRE, PENNYA INDUSTRIAL AREA, PHASE 1, BANGALORE 560058, INDIA
5. JAMES DERRYL
ITC R&D CENTRE, PENNYA INDUSTRIAL AREA, PHASE 1, BANGALORE 560058, INDIA
6. RAMAMURTHI SUREDH
ITC R&D CENTRE, PENNYA INDUSTRIAL AREA, PHASE 1, BANGALORE 560058, INDIA

Specification

TECHNICAL FIELD OF THE INVENTION
The present invention deals with a topical delivery of unstable cosmetic actives, more
specifically ascorbic acid, in free form and a system comprising the same which is effective
over all skin conditions (dry and normal).
BACKGROUND OF THE PRIOR ART
Ascorbic acid is one of the most important intracellular and extracellular antioxidant of body
and important for controlling many cellular and enzymatic activities. Ascorbic acid increases
the synthesis of collagen (act as cofactor for the enzymes, prolyl hydroxylase and lysyl
hydroxylase for the synthesis of collagen) and maintains the amount of collagen by
increasing the transcription rate of the genes associated with collagen synthesis. Several
studies have shown that topical application of ascorbic acid and its derivatives can repair the
photo-damaged skin. Darr, D., S. Combs, et al., "Topical vitamin C protects porcine skin
from ultraviolet radiation-induced damage", The British journal of dermatology 127(3): 247-
253 (1992); Darr. D., S. Dunston, et al., "Effectiveness of antioxidants (vitamin C and E)
with and without sunscreens as topical photoprotectants." Acta dermato-venereologica 76(4):
264-268 (1996). Quevedo, W. C, T. J. Holstein, et al., "Inhibition of UVR-induced tanning
and immunosuppression by topical applications of vitamins C and E to the skin of hairless
(hr/hr) mice."" Pigment cell research /sponsored by the European Society for Pigment Cell
Research and the International Pigment Cell Society 13(2): 89-98, (2000); Meves, A., S. N.
Stock, et al.. "Vitamin C derivative ascorbyl palmitate promotes ultraviolet-B-induced lipid
peroxidation and cytotoxicity in keratinocytes." The Journal of investigative dermatology
119(5): 1103-1108. (2002% Moison, R. M. W. and G. M. J. Beijersbergen van Henegouwen,
"Topical antioxidant vitamins C and E prevent UVB-radiation-induced peroxidation of
eicosapentaenoic acid in pig skin.", Radiation research 157(4): 402-409,(2002) Moison, R.
M. W., .1. M. Rijnkels, et al., "Topically applied vitamin C and cysteine derivatives protect
against UVA-induced photodegradation of suprofen in ex vivo pigskin.", Photochemistry and
photobiology 77(4): 343-348,(2003). Lin. F.-H., J.-Y. Lin, et al., "Ferulic acid stabilizes a
solution of vitamins C and E and doubles its photoprotection of skin.", The Journal of •
investigative dermatology 125(4): 826-832, (2005); Cho, H.-S., M.-H. Lee, et al., "Anti-
wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose
oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B
irradiation." Photodermatology. photoimmunology & photomedicine 23(5): 155-162, (2007);

Oresajo, C. T. Stephens, et al., "Protective effects of a topical antioxidant mixture containing
vitamin C. ferulic acid, and phloretin against ultraviolet-induced photodamage in human
skin.". Journal of cosmetic dermatology 7(4): 290-297, (2008); Raschke, T., U. Koop, et al.,
"Topical activity of ascorbic acid: from in vitro optimization to in vivo efficacy.", Skin
pharmacology and physiology 17(4): 200-206, (2004).
The main disadvantage of using ascorbic acid in solution is that it undergoes oxidation and
produce dehydro-l.-ascorbic acid as well as many degradation products. Tsao, C.S., Young,
M. A stabilised ascorbic acid solution, Med. Sci. Res. 24, 473-475, (1996). The oxidative
degradation process can be accelerated by several factors, such as high storage temperatures,
photo exposure, high pH values (>4.5) and the presence of dissolved oxygen. Roig, M.G.,
Rivera, Z.S.. Kennedy, J.F., A model study on rate of degradation of L-ascorbic acid during
processing using home-produced juice concentrates. Int. J. Food Sci. Nutr. 46, 107-115
(1995); Miyake. N., Miok, K., Kurata, T., Formation mechanism of mono dehydro-L-
ascorbic acid and superoxide anion in the autoxidation of L-ascorbic acid, Biosci. Biotech.
Biochcm. 61. 1693-1695. (1997). In addition, the reaction of ascorbic acid with oxygen is
strongly catalysed by metal ions, especially (Cupric and ferric ions) Niki, E., Vitamin C as an
antioxidant. World Rev. Nutr. Diet 64, 1-30 (1991), Buettner, G.R., Jurkiewicz, B.A.,
Chemistry and Biochemistry of ascorbic acid. In: Cadenas, E„ Paker, L. (Eds.), Handbook of
Antioxidants. Marcel Dekker, New York, pp. 91-115, (1996).
In the contemporan scenario, one of the ways to stabilize ascorbic acid is by derivatizing it.
The most common of these, sodium ascorbyl phosphate, magnesium ascorbyl phosphate and
ascorbyl-6-palmitate are enzymatically converted to L -ascorbic acid in cell, organ culture
(Nayama. S.. Takehana, M., Kanke, M., Itoh, S., Ogata, E., Kobayashi, S., Protective effects
of sodium- L -ascorbyl-2 phosphate on the development of UVB-induced damage in cultured
mouse skin. Biol. Pharm. Bull. 22, 1301-1305 (1999)) and/ or by ingestion; but do not
efficiently increase skin levels of L -ascorbic acid after topical application (Pinnell, S.R.,
Yang. H.S.. Omar. M, Riviere, N.M., DeBuys, H.V., Walker, L.C., et al., Topical L -ascorbic
acid: percutaneous absorption studies. Dermatol. Surg. 27, 137-142 (2001)). In addition, .
derivatisation leads to a reduced antioxidant efficacy. Moreover, the conversion of derivative
to its active form is mediated by in-situ enzymes, which are inactive in dry or damaged skin.
The present invention elucidates the solution for delivering ascorbic acid by maintaining its
inherent efficacy, applicable for all skin types.

Microfine particles of ascorbic acid was used to stabilize the same in anhydrous formulations,
which in turn was utilizedfor studying the effect of the same on neocollagenesis and
cytokeratin production in ex vivo human skin and the results showed neocollagenesis and
increased production of cytokeratin (Heber, G.K., Markovic, B., Hayes, A., An
immunohistological study of anhydrous topical ascorbic acid compositions on ex vivo human
skin. J. Cosmet. Dermatol. 5. 150-156. (2006)).
US 2005/ 220860Al teaches about cosmetic powders containing pure vitamin C by utilizing
multi encapsulation method, which changes to liquid, when sprayed over skin and slight
pressure is applied. The present invention stabilizes ascorbic acid in aqueous form, which
does not require external pressure and spray of water to liquefy it. The present invention finds
direct application for products in which there is no scope of applying shear forces (pressure)
on the skin (viz; face mask)
US 6020367 teaches a method for preparing stable, supersaturated solutions of ascorbic acid
in polyol vesicles. It teaches supersaturated ascorbic acid at a concentration of upto 25% by
weight of ascorbic acid stabilized inside polyol vehicle that has further been incorporated in
liposome.
Known processes making naturally photo-unstable compound such as ascorbic acid, includes
providing shielding mechanisms such as optical filters, colored or shiny bottle and special
packaging, which are cumbersome and not user friendly. Adapting this technology to
cosmetics comprising ascorbic acid is not feasible as ascorbic acid oxidizes at pH 7.0.
It has been surprisingly found that a chemical barrier between ascorbic acid and
oxygen/optical stimuli by entrapping the ascorbic acid inside liposome and appropriately
adjusting the internal and external pH stabilizes the active composition and delivers the same
appropriately.
OBJECT OF THE INVENTION
It is an object of the invention to overcome the drawbacks of the prior art.

It is another object of the present invention to provide a topical delivery system, which
prevents degradation of an unstable active (e.g. ascorbic acid aqueous solution at pH 7) by
encapsulating with liposome, which builds a barrier between environment and active.
It is another object of the present invention to provide system for improving the topical
availability of active antioxidant in skin.
It is yet another object of the present invention to provide system comprising pure ascorbic
acid for cosmetic applications, which is stable for more than a month.
It is further an object of the present invention to provide sustained topical delivery of
antioxidant.
It is further an object of the present invention to provide topical delivery of antioxidants (e.g.
Ascorbic acid) in a wide concentration range as required by individual, which is not
achievable by conventional ascorbic acid derivatives in presence of equivalent delivery
systems.
SUMMARY OF THE INVENTION
A stable liposomal composition of ascorbic acid comprising,
0.01% to about 20% by weight aqueous solution of ascorbic acid in a liposome such
that said ascorbic acid is pure and stable up to pH 7.0 in the said composition.
A process for preparing the liposomal composition of ascorbic acid comprising
a) dissolving phospholipids, sterol, surface-active polymers, fatty acids in
Ethanol.
b) solubilizing ascorbic acid in cooled boiled water
c) adding the ascorbic acid solution obtained from step (b) to the mixture
obtained from step (a) drop by drop under constant stirring condition.
d) mixing solution comprising surfactant and polyol and adding to the above
mixture obtained from step (c) under constant stirring.
e) adjusting pH of the solution to 6 to 7 using alkali

BRIEF DESCRIPTION OF THE ACCOMPANYING FIGURES
Figure. 1 illustrates the Stability of aqueous and liposomal form of ascorbic acid has been
measured in different experimental conditions (pH 7 at ambient condition) for seven weeks.
Figure. 2 illustrates the delivery of ascorbic acid from three different forms (aqueous form,
liposomal form of ascorbic acid and aqueous form of sodium ascorbyl phosphate) to different
skin depth
Figure. 3 illustrates the anti-oxidant activity of the liposomal L-ascorbic acid and liposomal
Na-ascorbyl phosphate in different skin depth
Figure. 4 illustrates the kinetics of release of liposomal ascorbic acid in skin after application
on volar forearm
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to delivery systems, more specifically, a phospholipid based
liposomal formulation containing antioxidant for treating human skin. In the present
invention stabilization of the aqueous solution of the active is achieved only by liposome, .
whereas the prior art uses polyol vehicle irrespective of liposome usage for stability. This
feature has not been recited by prior art. The inventors have tested the same for topical
delivery and have found it to be stable for up to seven weeks. Specimens not subjected to this
protocol normally starts degrading within 1 day.
Skin lacking proper barrier function becomes dry due to the transepidermal water loss. The
enzymes present in the epidermal layer become inactive due the absence of required level of
skin hydration. Most of the antioxidant derivatives used in the skin care formulation needs to
be enzymatically hydrolyzed to its active form. As the enzymes are not active for releasing
the active form of the antioxidant from its derivatives, the activity of the same might be
questionable. The present invention improves the availability of active antioxidant in skin
compared to its derivative. The present invention improves the sustained release of
antioxidant.
Accordingly the present invention provides a topical delivery system comprising liposome
encapsulating ascorbic acid. The liposome is formed from surfactants such as phospholipids,

cationic surfactants, anionic surfactants; sterols such as cholesterol; fatty acids and/ or
hydrophobically modified surface-active polymers.
The liposome formation was controlled by retarding movement of surfactant molecules in the
viscous medium, thereby increasing the encapsulation efficiency for the ascorbic acid.
The invention provides a water-soluble form of pure ascorbic acid, which is stable up to a pH
7.0 that is much beyond its natural stability at pH 3.0. The invention provides ascorbic acid .
that is chemically pure and thus effective in cosmetic applications.
The ascorbic acid can include one selected from the group comprising L-ascorbic acid, D-
ascorbic acid. D-araboascorbic acid. L-araboascorbic acid and combinations thereof.
Preferably, the ascorbic acid is L- ascorbic acid.
The amount of ascorbic acid present in the aqueous solution is about 0.01% to about 20% by
weight most preferably from 1% to 5% by weight.
The surfactant in the present invention is selected from the group of phospholipids such as
phosphotidycholine, phosphotidylethanolamine; cationic surfactants such as Dodecyl (C12),
myryltoyl (C14). palmitoyl (C16) and stearyl (C18) trimethyl ammonium chloride (C12-18TC),
Dodecyl (C12). myryltoyl (C14), palmitoyl (C16) and stearyl (C18) trimethyl ammonium
bromide (C12-18TAB). Most preferably the surfactant is selected from phosphotidylcholine,
phosphatidylethanolamine and CTC.
The surfactant in the present invention is present in the amount of 0.01 to 10% by weight;
preferably from 0.1 to 5% by weight ; most preferably from 0.1 to 1% by weight.
The sterols in the present invention are selected from the group of phytosterols (e.g.
stigmasterol. ergostcrols, sitosterols, campesterol) and cholesterol and their derivatives; most
preferably the sterol is cholesterol.
The sterol in the present invention is present in the amount of 0.1 to 30% by weight;
preferably from 5 to 20% by weight; most preferably from 10 to 15% by weight.

1 he fatty acids in the present invention are selected from the group of long chain fatty acids,
preferably straight chain fatty acids such as Myristic acid, Palmitic acid. Stearic acid,
Arachidic acid: most preferably stearic acid and palmitic acid
The Fatty acids in the present invention is present in the amount of 0.01 to 10% by weight;
more preferably 1 to 8% by weight; most preferably 5 to 7% by weight.
The surface-active polymers in the present invention is selected from the group of
hydrophobically modified polymers such as hydrophobically modified polysaccharides, •
hydrophobically modified polyols; preferably hydrophobically modified polyols and most
preferably fatty acyl derivatives of polyols such as fatty acyl derivatives of polyethylene
glycol, PEG22.
The surface-active polymers in the present invention are present in the amount of 0.01 to 20%
by weight; preferably 1 to 8% by weight and most preferably 5 to 8% by weight.
Liposomal formulation of ascorbic acid of the present invention, when applied on skin of the
volar forearm of different panelists showed good penetrability and anti oxidants activities
over a period of 4 hrs.
The ascorbic acid solution can be readily used in compositions containing other cosmetic and
pharmaceutical agents, e.g., anti-fungals, vitamins, sunscreens, retinoids, antihistamines,
depigmenting agents, anti-inflammatory agents, anesthetics, surfactants, emulsifiers,
stabilizers, preservatives, antiseptics, emollients, thickeners, lubricants, humectants, chelating
agents, fragrances, colorants and skin penetration enhancers.
The present invention is used in any form of personal care (such as but not limited to creams,
lotions, face mask, serums, face wash, wipes) formulations. The present systems can also be
incorporated in other formulation containing sunscreens, fairness, conditioning, moisturizing.
The invention is now described by way of illustrative non-limiting examples with reference
to figures.
Example 1
Formulation 1:
Components of liposome:

The liposome is made of surfactants (4% by weight) (e.g. phospholipids, cationic surfactants,
anionic surfactants), cholesterol (0.3% by weight), fatty acids (0.14% by weight), surface-
active polymers (1% by weight) (e.g. hydrophobically modified polymers) and ascorbic acid
3.5% by weight.
Ascorbic acid solution
Ascorbic acid used is 3.5% L-ascorbic acid (obtained from Sigma-Aldrich, 99%purity)
solubilized in cooled boiled deionized water.
Example 2: Process Steps
Method of Preparation of Liposomal ascorbic acid:
To prepare a l00gm of liposomal solution containing 3.5%, by weight of ascorbic acid, ,
phospholipid (2% by weight), cholesterol (0.3% by weight), hydrophobically modified
polymer (e.g. PEG-22) (1% by weight), fatty acids (e.g. Stearic acid) (0.14% by weight) were
dissolved in Ethanol (5% by weight). L-Ascorbic Acid ( 3.5% by weight) solutions in
cooled boiled water was added to the above mixer drop by drop (1 to 2mL/min) under
constant stirring condition. Eight grams (8gm) of a mixed solution comprising of a cationic or
anionic surfactant (e.g. 2% CTC-30) and polyol (e.g 6% glycerin) was added to the above
mixture (8()gm) under constant stirring. The pH of the solution was adjusted to 6 to 7 using
alkali (e.g. NaOH). The total weight was adjusted to 100gm by cooled boiled water.
Example 3
Tape stripping test:
The penetration and antioxidant activity of aqueous solution of ascorbic acid and liposomal
ascorbic acid was determined using tape stripping. Known volume (20µl) of aqueous solution
of ascorbic acid in water and ascorbic acid in liposomes were applied on the skin of volar
fore arm and allowed to dry completely for 20minutes. Tape strips of samples were collected
using adhesive tapes (Corneofix) from applied sites and unapplied site (baseline) after
washing the sites with known volume of water. The tapes striped out were kept in centrifuge
tubes (Eppendorf) and known volume of phosphate buffer saline (PBS) was added to all the
tubes. All the tubes were vortexed vigorously for 20 sec to extract ascorbic acid in the buffer
solution from the tapes. The absorbance was measured at 265nm spectrophotometrically. The
concentration of ascorbic acid was calculated from the concentration Vs absorbance standard
graph. The antioxidant activity of ascorbic acid from aqueous and from liposomal form in

Example 4:
Comparative formulation:
Ascorbic acid (AA) with /without liposome to show stability at pH 7
Stability of aqueous and liposomal form of ascorbic acid containing 3.5% by weight ascorbic
acid (L- Ascorbic acid in liposomal and Free form) has been measured in different
experimental conditions (pH 7 at ambient condition) for seven weeks, which is provided in
figure I.
Liposomal ascorbic acid was found to be stable compared to its aqueous solution form over
seven weeks at ambient temperature.
Example 5
Delivery of ascorbic acid from three different forms (aqueous form, liposomal form of
ascorbic acid and aqueous form of sodium ascorbyl phosphate) to different skin depth
The delivery of aqueous form, liposomal form of ascorbic acid containing 3.5% by weight
ascorbic acid and aqueous form of the sodium ascorbyl phosphate in different skin depth was
determined using tape-striping method as described earlier. The amount of ascorbic acid in
each tape-strip was determined using DPPH assay
As can be seen from the graph in figure 2, the liposomal form delivers significantly more
amount of ascorbic acid at different skin depths, when compared to derivative and non-
encapsulated form.
Example 6
Comparison of the anti-oxidant activity of the liposomal L-ascorbic acid and liposomal
Na-aseorbyl phosphate in different skin depth
The antioxidant activity of the liposomal L-ascorbic acid containing 3.5% by weight ascorbic
acid and liposomal Na-ascorbyl phosphate were compared after application in skin were
determined using tape-stripping followed by DPPH free radical scavenging assay. Here

known volume of liposomal ascorbic acid solution and Sodium Ascorbyl Phosphate solution
was applied on different regions of volar fore arm. The applied liquid solution was allowed to
absorb into the skin for 20min. The sites were washed with fixed volume of distilled water
and allowed to dry. Six different tape strips were taken from each site of application along
with an unapplied site (baseline) and the actives were extracted in phosphate buffer. The
percentage antioxidant activity in each extracted solution was determined from the
measurement of the free radical scavenging activity of DPPH.
The percentage of free radical scavenging activity of the liposomal L-ascorbic acid was
higher than the liposomal Na-ascorbyl phosphate used for the study. It can be inferred from
the data provided in figure 3 that ascorbic acid derivatives do not show significant anti-
oxidant efficacy even when the penetration is enhanced by liposomal encapsulation.
Example 7
Kinetics of Release of liposomal ascorbic acid in skin after application on volar forearm
The delivery of ascorbic acid from liposome containing 3.5% by weight ascorbic acid to
different skin depths over a period of time (4 to 5 hrs) was studied using tape-stripping
method. The amount of ascorbic acid in skin was measured using DPPH scavenging assay.
The results as provided in figure 4 showed that the DPPH scavenging activity for liposomal
ascorbic acid persists more than four hours. On a five-hours study liposomal ascorbic acid
showed free radical scavenging activity in all the five strips over baseline. The liposomal -
ascorbic acid showed availability at different skin depths over a time line of four hours.
Example 8
Efficacy of the present process over the conventional protocol of liposome preparation
To check the efficacy of the present process over the conventional protocol of liposome
preparation (Delivery system handbook for personal care and cosmetic products: technology .
By Meyer R. Rosen. 2005), evaluation of the conventional methods of liposome preparation
was done in-house. The data generated in-house for conventional protocol matches with the
data reported in literature. The uses of these liposomes in formulation are limited due to their
limited stability and encapsulation efficiency.

The liposome prepared in the present invention containing 3.5% by weight ascorbic acid has
higher encapsulation efficiency. Besides the liposome is stable itself and remains stable when
incorporated in formulation.
Table I mentioned below aim at representing the differences of present invention from
conventional protocol, along with their associated benefits:


We claim
1) A stable liposomal composition of ascorbic acid comprising, 0.01% to about 20% by
weight aqueous solution of ascorbic acid in a liposome such that said ascorbic acid is
pure and stable up to a pH 7.0 in the said composition.
2) The stable liposomal composition as claimed in claim 1, wherein said aqueous
solution of ascorbic acid comprises preferably 1% to 5% by weight of ascorbic acid.
3) The stable liposomal composition as claimed in any of the claim 1 or 2, wherein said
liposome comprises
0.01 to 10% by weight surfactants,
0.01 to 50% by weight sterol,
0.01 to 10% by weight fatty acids,
0.01 to 20% by weight surface-active polymers and combinations thereof
4) The stable liposomal composition as claimed in claim 3, wherein said surfactant is
selected from phospholipids, cationic surfactants, and combinations thereof.
5) The stable liposomal composition as claimed in claim 4, wherein said phospholipids
is selected from phosphotidylcholine and phosphotidylethanolamine
6) The stable liposomal composition as claimed in any of claim 4 or 5, wherein said
cationic surfactants is selected from Dodecyl (C12), myryltoyl (C14), palmitoyl (C16)

and stearyl (C18) trimethyl ammonium chloride (C12-18TC), Dodecyl (C12), myryltoyl
(C14). palmitoyl (C16) and stearyl (C18) trimethyl ammonium bromide (C12-18TAB)
7) The stable liposomal composition as claimed in any of claim 3 to 6, wherein said
surfactants is present in the amount of 0.01 to 10% by weight; preferably 0.1 to 5% by
weight: more preferably 0.1 to 1% by weight.
8) The stable liposomal composition as claimed in claim 3, wherein said sterol is
selected from phytosterols, cholesterol and their derivatives and combinations thereof
9) The stable liposomal composition as claimed in claim 8, wherein said phytosterols is •
• selected from stigmasterol, ergosterols, sitosterols and campesterol.
10) The stable liposomal composition as claimed in any of claim 3 or 8, wherein said
sterol is cholesterol.
11) The stable liposomal composition as claimed in any of claim 3 and 8 to 10, wherein
said sterol is present in the amount of 0.1 to 30% by weight, preferably 5 to 20% by
weight, more preferably 10 to 15% by weight
12) The stable liposomal composition as claimed in claim 3, wherein said fatty acids are
selected from long chain fatty acids and straight chain fatty acids
13) The stable liposomal composition as claimed in claim 12, wherein said straight chain
fatty acids is selected from Myristic acid. Palmitic acid, Stearic acid. Arachidic acid
14) The stable liposomal composition as claimed in any of claim 12 or 13. wherein said
straight chain fatty acids is selected from palmitic and stearic acids .
15) The stable liposomal composition as claimed in any of claim 3 and 12 to 14, wherein
said fatty acid is present in the amount of 0.01 to 10% by weight, preferably from 1 to
8% by weight, more preferably from of 5 to 7% by weight
16) The stable liposomal composition as claimed in claim 3, wherein said surface-active
polymers is hydrophobically modified polymers, selected from hydrophobicaly

modified polysaccharides, PEG22, preferably hydrophobically modified polyols and
most preferably fatty acyl derivatives of polyols.
17) The stable liposomal composition as claimed in any claim 3 or 16 wherein the
surface-active polymers are present in the amount of 0.01 to 20% by weight;
preferably 1 to 8% by weight; more preferably 5 to 8% by weight.
18) The stable liposomal composition as claimed in any of the preceding claims wherein
the said composition is a cosmetic composition.
19) A process for preparing the liposomal composition of ascorbic acid comprising
a. dissolving sterol, surface-active polymers, fatty acids in ethanol.
b. Dissolving ascorbic acid in cooled boiled water
c. adding the ascorbic acid solution obtained from step (b) to the mixture
obtained from step (a) drop by drop (I -2 ml/minute) under constant stirring
condition.
d. mixing solution comprising surfactant and polyol and adding to the above
mixture obtained from step (c) under constant stirring.
e. adjusting pH of the solution to 6 to 7 using alkali

A topical delivery system comprising liposome encapsulating ascorbic acid wherein the
liposome is formed from surfactants (e.g. phospholipids, cationic surfactants, anionic
surfactants), sterols such as cholesterol, fatty acids and/ or hydrophobically modified surfaceactive
polymers. The stable liposomal composition of ascorbic acid comprising, 0.01% to about
20% by weight aqueous solution of ascorbic acid wherein said ascorbic acid is pure and stable up
to pH 7.0. A process for preparing the liposomal composition of ascorbic acid comprising (a)
dissolving sterol, surface-active polymers, fatty acids in ethanol, (b) ascorbic acid solution in
cooled boiled water, (c) adding the ascorbic acid solution obtained from step (b) to the mixture
obtained from step (a) drop by drop under constant stirring condition, (d) mixing solution
comprising surfactant and surface-active polymer and adding to the above mixture obtained from .
step (c) under constant stirring and (e) adjusting pH of the solution to 6 to 7 using alkali.

Documents

Application Documents

# Name Date
1 132-KOL-2010-RELEVANT DOCUMENTS [25-03-2020(online)].pdf 2020-03-25
1 abstract-132-kol-2010.jpg 2011-10-06
2 132-KOL-2010-FORM 4 [20-05-2019(online)].pdf 2019-05-20
2 132-kol-2010-specification.pdf 2011-10-06
3 132-KOL-2010-RELEVANT DOCUMENTS [31-03-2019(online)].pdf 2019-03-31
3 132-kol-2010-gpa.pdf 2011-10-06
4 132-KOL-2010-RELEVANT DOCUMENTS [21-02-2018(online)].pdf 2018-02-21
4 132-kol-2010-form 3.pdf 2011-10-06
5 132-KOL-2010-PatentCertificate01-08-2017.pdf 2017-08-01
5 132-kol-2010-form 2.pdf 2011-10-06
6 132-KOL-2010-PatentCertificateCoverLetter.pdf 2017-08-01
6 132-KOL-2010-FORM 18.pdf 2011-10-06
7 Abstract [25-05-2017(online)].pdf 2017-05-25
7 132-kol-2010-form 1.pdf 2011-10-06
8 Examination Report Reply Recieved [25-05-2017(online)].pdf 2017-05-25
8 132-KOL-2010-FORM 1-1.1.pdf 2011-10-06
9 132-kol-2010-drawings.pdf 2011-10-06
9 Other Document [25-05-2017(online)].pdf 2017-05-25
10 132-kol-2010-description (complete).pdf 2011-10-06
10 132-KOL-2010-FER.pdf 2016-11-25
11 132-KOL-2010-(14-06-2013)-CORRESPONDENCE.pdf 2013-06-14
11 132-kol-2010-correspondence.pdf 2011-10-06
12 132-kol-2010-abstract.pdf 2011-10-06
12 132-KOL-2010-CORRESPONDENCE-1.1.pdf 2011-10-06
13 132-kol-2010-claims.pdf 2011-10-06
14 132-kol-2010-abstract.pdf 2011-10-06
14 132-KOL-2010-CORRESPONDENCE-1.1.pdf 2011-10-06
15 132-KOL-2010-(14-06-2013)-CORRESPONDENCE.pdf 2013-06-14
15 132-kol-2010-correspondence.pdf 2011-10-06
16 132-kol-2010-description (complete).pdf 2011-10-06
16 132-KOL-2010-FER.pdf 2016-11-25
17 Other Document [25-05-2017(online)].pdf 2017-05-25
17 132-kol-2010-drawings.pdf 2011-10-06
18 132-KOL-2010-FORM 1-1.1.pdf 2011-10-06
18 Examination Report Reply Recieved [25-05-2017(online)].pdf 2017-05-25
19 Abstract [25-05-2017(online)].pdf 2017-05-25
19 132-kol-2010-form 1.pdf 2011-10-06
20 132-KOL-2010-PatentCertificateCoverLetter.pdf 2017-08-01
20 132-KOL-2010-FORM 18.pdf 2011-10-06
21 132-KOL-2010-PatentCertificate01-08-2017.pdf 2017-08-01
21 132-kol-2010-form 2.pdf 2011-10-06
22 132-KOL-2010-RELEVANT DOCUMENTS [21-02-2018(online)].pdf 2018-02-21
22 132-kol-2010-form 3.pdf 2011-10-06
23 132-KOL-2010-RELEVANT DOCUMENTS [31-03-2019(online)].pdf 2019-03-31
23 132-kol-2010-gpa.pdf 2011-10-06
24 132-kol-2010-specification.pdf 2011-10-06
24 132-KOL-2010-FORM 4 [20-05-2019(online)].pdf 2019-05-20
25 132-KOL-2010-RELEVANT DOCUMENTS [25-03-2020(online)].pdf 2020-03-25
25 abstract-132-kol-2010.jpg 2011-10-06

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