Indian Patents. 216857:FORMULATION CONTAINING MELATONIN GINKGO BILOBA AND BIOTIN.

Title of Invention	FORMULATION CONTAINING MELATONIN GINKGO BILOBA AND BIOTIN.
Abstract	The present invention relates to a composition which comprises as active ingredients a combination of melatonin, ginkgo biloba and biotin. The composition is particularly suitable for producing formulations for topical application in the hair.

Full Text	Description 5 The present invention relates to a composition which comprises as active ingredients a combination of melatonin, ginkgo biloba and biotin. The composition is particularly suitable for producing formulations for 10 topical application in the hair. The use of melatonin for beneficially influencing hair growth is known. Melatonin has a stimulating effect on hair growth due to the selective interaction with 15 proliferating cells of the hair follicies which control the growth of hair. This stimulating effect can be observed with the use of different concentrations of melatonin. 20 US-Patent 5,952,373 describes a method for the treatment of skin, in which a composition which comprises as active ingredient one or more flavonoids is applied. There is no reference to the use of melatonin as active ingredient for improving hair 25 growth. US patent application US 2002/0061370 discloses a composition for the amelioration of hearing loss or tinnitus. This composition, which is administered in 30 form of a tablet, comprises a large number of active ingredients, optionally also including melatonin, biotin or ginkgo biloba. There is no reference to the use for improving hair growth or to topical application. 35 It has surprisingly been found in the investigations leading to the present invention that the addition of ginkgo biloba and biotin in simultaneous use of - 2 - melatonin enhance the effect of melatonin, and retention of melatonin on the surface of the scalp is increased. 5 One aspect of the present invention is thus a composition which comprises as active ingredients (a) melatonin or a derivative thereof, (b) ginkgo biloba as extract or/and one or more constituents thereof and (c) biotin. The composition is preferably a topical 10 formulation suitable for pharmaceutical or/and cosmetic uses, in particular for application to the scalp. The composition of the invention comprises a combination of active ingredients. The first component 15 of this combination is melatonin or a melatonin derivative. Melatonin derivatives are preferably selected from 5-methoxytryptamine, 5-methoxytryptophan, 5-methoxytryptophol, 5-methoxyindole-3-acetic acid and 6-hydroxymelatonin. Besides these substances it is also 20 possible to employ physiologically acceptable salts, esters and complex compounds thereof. The second component of the composition is ginkgo biloba. Ginkgo biloba has a beneficial influence on 25 various metabolic functions, A further advantageous property of ginkgo is the enhancement of the potential for trapping free radicals. A ginkgo biloba is preferably used as extract, in particular as dry extract, or/and one or more constituents thereof. Dry 30 extracts from ginkgo leaves are particularly suitable for use of the composition of the invention. A further component of the composition of the invention is biotin. Biotin displays its effect for example as 35 coenzyme in fatty acid and aminc acid metabolism, e.g, in transcarboxylation reactions. The concentration of the active ingredients in the composition can be varied within wide limits - - 3 - depending on the use. It is beneficial for the concentrations of the active ingredients each to be independently in the range between 0.0001% (weight) to 1% (weight) based on the total weight of the 5 composition. The concentration of melatonin or a melatonin derivative is preferably 0.001% (weight) to 0-01% (weight). The concentration of ginkgo biloba is preferably 0.01% (weight) to 0.1% (weight). The concentration of biotin is preferably 0.002% (weight) 10 to 0.05% (weight). Preferably about 0.001 mg to about 10 mg, preferably about 0.01 mg to about 1 mg, of melatonin or melatonin derivative are administered per application. 15 The three active ingredient components of the composition of the invention display a profile of effects which promotes hair growth, provides protection from aging, improves hair thickness or/and reduces the 20 teiogen rate. The effect of melatonin on the hair follicle is surprisingly enhanced by the combination with ginkgo biloba and biotin. It is thus possible to employ even very low concentrations of melatonin, for example about 0.001-10 mg, preferably about 0.01-1 mg 25 per application, with a satisfactory effect. The combination of melatonin, ginkgo biloba and biotin can be administered in a suitable carrier system. The active ingredients are preferably present as solution 30 or/and dispersion in a liquid, semisolid or solid carrier system. Examples of suitable carrier systems are liquids such as water or aqueous buffer solutions, physiologically tolerated organic solvents such as ethanol or combinations thereof, oil-water emulsions, 35 water-oil emulsions, fats, polyethylene glycols, propylene glycols, glyceral, emulsifiers or combinations thereof, and other carriers or excipients used in pharmaceutical and cosmetic formulations. - 4 - The use of an aqueous carrier system, i.e., a carrier system with a water content of 50% (weight) or more, in particular of 60% (weight) or more, is preferred. The pH of an aqueous carrier system is preferably adjusted 5 in a range between pH 3 and pH 6, particularly preferably in the range from pH 3.5 and pH 4. These carrier systems advantageously enable targeted delivery of the active ingredients to the hair 10 follicle. The placement of the active ingredients in the hair follicle is optimized thereby. Controlled absorption of the melatonin, qinkgo biloba and biotin active ingredients can moreover be made possible by the carrier system. 15 The processing of melatonin with ginkgo biloba and biotin in suitable carrier systems may in addition lead to a prevention or delay of melatonin absorption. The normal human plasma level is not influenced thereby. In 20 addition, a longer-lasting effect of the active. ingredients can be achieved. Stable formulations used in cosmetics, especially in the form of cosmetics solutions, can be obtained by 25 formulation in a carrier system. In the use of specific formulation systems such as liposomes, nanosomes or solid inclusion carriers such as agarose it is possible to obtain compositions which 30 permit controlled delivery of at least one of the active ingredients, in particular of all the active ingredients. The compositions of the inversion are particularly 35 suitable for pharmaceutical or/and cosmetic applications, for example in hair. The compositions may be in the form of a solution, suspension, emulsion, microemulsion, nanosystem, cream, gel, lotion, spray, foam or ointment or any other form suitable for topical - 5 - applications. They are normally employed in a packaging or application system selected from tubes, bottles, spray bottles, patches, sponges and textile or plastics carriers and other systems suitable for application in 5 the hair. A particularly preferred packaging system are single-dose ampules which provide a dosage unit for one application. The ampules may be fabricated from various materials, e.g. from glass or plastics. Plastics ampules are particularly preferred because plastics 10 ampules ensure safe and satisfactory handling. Besides the active ingredients, the compositions of the invention may comprise one or more cosmetic or/and pharmaceutical excipients or additives, for example 15 thickeners, minerals, oils, vitamins, e.g. vitamin A, especially in the form of retinoic acid, or fragrances. The combination preparations of the invention are recommended in particular for application in the, 20 evening and display their effect in particular during, the night. With this mode of application, the effect of the composition is particularly strong. The compositions of the invention are particularly suitable for stimulation of the hair follicles and a beneficial 25 influence on hair growth. The treatment takes place in particular in topical applications suitable for use in the hair, which comprise the appropriate concentrations suitable for 30 the particular purpose of use of the active. ingredients. The composition of the invention can be employed for promoting hair growth, in particular for the prevention 35 or/and treatment of alopecia in men or in women. Particularly preferred indications are male-type androgenic alopecia, female-type androgsnic alopecia, male-type diffuse alopecia and female-type diffuse alopecia. - 6 - The invention is further illustrated by the following example. 5 Example: Composition of a formulation, of the invention with the active ingredients melatonin, ginkgo biloba and biotin. The composition comprises 0.05% by weight of ginkgo 10 biloba dry extract, 0.01% by weight of biotin, 0.0033% by weight of melatonin and further additives, water and ethanol. The pH of the composition is between 3.5 and 4 . WO 2004/039454 - 7 - PCT/EP2003/012097 Claims 1. A composition, characterized in that 5 it comprises as active ingredients (a) melatonin ox a derivative thereof, (b) ginkgo biloba and (c) biotin. 10 2. The composition as claimed in claim 1, characterized in that it comprises melatonin or a melatonin derivative selected from 5-methoxytryptamine, 5-methoxy- tryptophan, 5-methoxytryptophol, 5-methoxyindole- 15 3-acetic acid and 6-hydroxyimelatonin, and physiologically acceptable salts, esters and complex compounds thereof. 3. The composition as claimed in claim 1 or 2, 20 characterized in that it comprises ginkgo biloba as dry extract or/and one or more constituents thereof. 4 The composition as claimed in any of the preceding. 25 claims, characterized in that the concentration or active ingredients is in each case in the range between 0.0001% (by weight) and 1% (by weight) based on the total weight of the 30 composition. 5. The composition as claimed in any of the preceding claims. characterized in that 35 the active ingredients are present as solution or/and dispersion in a liquid, semisolid or solid carrier system. - 8 - 6. The composition as claimed in any of the preceding claims, characterised In that it permits controlled delivery of at least one of 5 the active ingredients. 7. The composition as claimed in any of the preceding claims for pharmaceutical or/and cosmetic applications. 10 8. The composition as claimed in any of claims 1 to 1 as topical formulation. 9. The composition as claimed in claim 7 or 6 for use 15 in the hair. 10. The composition as claimed in claim 8 or 9, characterised in that the transdermal absorption of at least one of the 20 active ingredients is controllable. 11. The composition as claimed in any of the preceding claims as solution, suspension, emulsion, microemulsian, nanosystem, cream, gel, lotion, 25 spray, foam or ointment. 12. The composition as claimed in any of the preceding, claims in a packaging or application system selected from single-dose ampules made of plastics 30 or glass, tubes, bottles, spray bottles, patches, sponges and textile or plastics carriers. 13. The composition as claimed in any of the preceding claims for enhancing the hair follicle-stimulating 35 effect of melatonin through the addition of ginkgo biloba and biotin. 14. The use of a composition as claimed in arty of the preceding claims for promoting hair growth. - 9 - 15. The use as claimed In claim 14 for producing an agent for the prevention or/and treatment of alopecia. 5 16. The use as claimed in claim 15 for the treatment of alopecia in men. 17. The use as claimed in claim 15 for the treatment 10 of alopecia in women. 18. The use as claimed in any of claims 14 to 17, characterised in that from 0.001 mg to 10 mg of melatonin are 15 administered per application. 19. The use as claimed in claim 18, characterized in that from 0.01 mg to 1 mg of melatonin are administered 20 per application. The present invention relates to a composition which comprises as active ingredients a combination of melatonin, ginkgo biloba and biotin. The composition is particularly suitable for producing formulations for topical application in the hair.

Full Text

Description
5
The present invention relates to a composition which
comprises as active ingredients a combination of
melatonin, ginkgo biloba and biotin. The composition is
particularly suitable for producing formulations for
10 topical application in the hair.
The use of melatonin for beneficially influencing hair
growth is known. Melatonin has a stimulating effect on
hair growth due to the selective interaction with
15 proliferating cells of the hair follicies which control
the growth of hair. This stimulating effect can be
observed with the use of different concentrations of
melatonin.
20 US-Patent 5,952,373 describes a method for the
treatment of skin, in which a composition which
comprises as active ingredient one or more flavonoids
is applied. There is no reference to the use of
melatonin as active ingredient for improving hair
25 growth.
US patent application US 2002/0061370 discloses a
composition for the amelioration of hearing loss or
tinnitus. This composition, which is administered in
30 form of a tablet, comprises a large number of active
ingredients, optionally also including melatonin,
biotin or ginkgo biloba. There is no reference to the
use for improving hair growth or to topical
application.
35
It has surprisingly been found in the investigations
leading to the present invention that the addition of
ginkgo biloba and biotin in simultaneous use of

- 2 -
melatonin enhance the effect of melatonin, and
retention of melatonin on the surface of the scalp is
increased.
5 One aspect of the present invention is thus a
composition which comprises as active ingredients (a)
melatonin or a derivative thereof, (b) ginkgo biloba as
extract or/and one or more constituents thereof and
(c) biotin. The composition is preferably a topical
10 formulation suitable for pharmaceutical or/and cosmetic
uses, in particular for application to the scalp.
The composition of the invention comprises a
combination of active ingredients. The first component
15 of this combination is melatonin or a melatonin
derivative. Melatonin derivatives are preferably
selected from 5-methoxytryptamine, 5-methoxytryptophan,
5-methoxytryptophol, 5-methoxyindole-3-acetic acid and
6-hydroxymelatonin. Besides these substances it is also
20 possible to employ physiologically acceptable salts,
esters and complex compounds thereof.
The second component of the composition is ginkgo
biloba. Ginkgo biloba has a beneficial influence on
25 various metabolic functions, A further advantageous
property of ginkgo is the enhancement of the potential
for trapping free radicals. A ginkgo biloba is
preferably used as extract, in particular as dry
extract, or/and one or more constituents thereof. Dry
30 extracts from ginkgo leaves are particularly suitable
for use of the composition of the invention.
A further component of the composition of the invention
is biotin. Biotin displays its effect for example as
35 coenzyme in fatty acid and aminc acid metabolism, e.g,
in transcarboxylation reactions.
The concentration of the active ingredients in the
composition can be varied within wide limits -

- 3 -
depending on the use. It is beneficial for the
concentrations of the active ingredients each to be
independently in the range between 0.0001% (weight) to
1% (weight) based on the total weight of the
5 composition. The concentration of melatonin or a
melatonin derivative is preferably 0.001% (weight) to
0-01% (weight). The concentration of ginkgo biloba is
preferably 0.01% (weight) to 0.1% (weight). The
concentration of biotin is preferably 0.002% (weight)
10 to 0.05% (weight).
Preferably about 0.001 mg to about 10 mg, preferably
about 0.01 mg to about 1 mg, of melatonin or melatonin
derivative are administered per application.
15
The three active ingredient components of the
composition of the invention display a profile of
effects which promotes hair growth, provides protection
from aging, improves hair thickness or/and reduces the
20 teiogen rate. The effect of melatonin on the hair
follicle is surprisingly enhanced by the combination
with ginkgo biloba and biotin. It is thus possible to
employ even very low concentrations of melatonin, for
example about 0.001-10 mg, preferably about 0.01-1 mg
25 per application, with a satisfactory effect.
The combination of melatonin, ginkgo biloba and biotin
can be administered in a suitable carrier system. The
active ingredients are preferably present as solution
30 or/and dispersion in a liquid, semisolid or solid
carrier system. Examples of suitable carrier systems
are liquids such as water or aqueous buffer solutions,
physiologically tolerated organic solvents such as
ethanol or combinations thereof, oil-water emulsions,
35 water-oil emulsions, fats, polyethylene glycols,
propylene glycols, glyceral, emulsifiers or
combinations thereof, and other carriers or excipients
used in pharmaceutical and cosmetic formulations.

- 4 -
The use of an aqueous carrier system, i.e., a carrier
system with a water content of 50% (weight) or more, in
particular of 60% (weight) or more, is preferred. The
pH of an aqueous carrier system is preferably adjusted
5 in a range between pH 3 and pH 6, particularly
preferably in the range from pH 3.5 and pH 4.
These carrier systems advantageously enable targeted
delivery of the active ingredients to the hair
10 follicle. The placement of the active ingredients in
the hair follicle is optimized thereby. Controlled
absorption of the melatonin, qinkgo biloba and biotin
active ingredients can moreover be made possible by the
carrier system.
15
The processing of melatonin with ginkgo biloba and
biotin in suitable carrier systems may in addition lead
to a prevention or delay of melatonin absorption. The
normal human plasma level is not influenced thereby. In
20 addition, a longer-lasting effect of the active.
ingredients can be achieved.
Stable formulations used in cosmetics, especially in
the form of cosmetics solutions, can be obtained by
25 formulation in a carrier system.
In the use of specific formulation systems such as
liposomes, nanosomes or solid inclusion carriers such
as agarose it is possible to obtain compositions which
30 permit controlled delivery of at least one of the
active ingredients, in particular of all the active
ingredients.
The compositions of the inversion are particularly
35 suitable for pharmaceutical or/and cosmetic
applications, for example in hair. The compositions may
be in the form of a solution, suspension, emulsion,
microemulsion, nanosystem, cream, gel, lotion, spray,
foam or ointment or any other form suitable for topical

- 5 -
applications. They are normally employed in a packaging
or application system selected from tubes, bottles,
spray bottles, patches, sponges and textile or plastics
carriers and other systems suitable for application in
5 the hair. A particularly preferred packaging system are
single-dose ampules which provide a dosage unit for one
application. The ampules may be fabricated from various
materials, e.g. from glass or plastics. Plastics
ampules are particularly preferred because plastics
10 ampules ensure safe and satisfactory handling.
Besides the active ingredients, the compositions of the
invention may comprise one or more cosmetic or/and
pharmaceutical excipients or additives, for example
15 thickeners, minerals, oils, vitamins, e.g. vitamin A,
especially in the form of retinoic acid, or fragrances.
The combination preparations of the invention are
recommended in particular for application in the,
20 evening and display their effect in particular during,
the night. With this mode of application, the effect of
the composition is particularly strong. The
compositions of the invention are particularly suitable
for stimulation of the hair follicles and a beneficial
25 influence on hair growth.
The treatment takes place in particular in topical
applications suitable for use in the hair, which
comprise the appropriate concentrations suitable for
30 the particular purpose of use of the active.
ingredients.
The composition of the invention can be employed for
promoting hair growth, in particular for the prevention
35 or/and treatment of alopecia in men or in women.
Particularly preferred indications are male-type
androgenic alopecia, female-type androgsnic alopecia,
male-type diffuse alopecia and female-type diffuse
alopecia.

- 6 -
The invention is further illustrated by the following
example.
5 Example: Composition of a formulation, of the invention
with the active ingredients melatonin, ginkgo
biloba and biotin.
The composition comprises 0.05% by weight of ginkgo
10 biloba dry extract, 0.01% by weight of biotin, 0.0033%
by weight of melatonin and further additives, water and
ethanol. The pH of the composition is between 3.5 and
4 .

WO 2004/039454 - 7 - PCT/EP2003/012097
Claims
1. A composition,
characterized in that
5 it comprises as active ingredients
(a) melatonin ox a derivative thereof,
(b) ginkgo biloba and
(c) biotin.
10 2. The composition as claimed in claim 1,
characterized in that
it comprises melatonin or a melatonin derivative
selected from 5-methoxytryptamine, 5-methoxy-
tryptophan, 5-methoxytryptophol, 5-methoxyindole-
15 3-acetic acid and 6-hydroxyimelatonin, and
physiologically acceptable salts, esters and
complex compounds thereof.
3. The composition as claimed in claim 1 or 2,
20 characterized in that
it comprises ginkgo biloba as dry extract or/and
one or more constituents thereof.
4 The composition as claimed in any of the preceding.
25 claims,
characterized in that
the concentration or active ingredients is in each
case in the range between 0.0001% (by weight) and
1% (by weight) based on the total weight of the
30 composition.
5. The composition as claimed in any of the preceding
claims.
characterized in that
35 the active ingredients are present as solution
or/and dispersion in a liquid, semisolid or solid
carrier system.

- 8 -
6. The composition as claimed in any of the preceding
claims,
characterised In that
it permits controlled delivery of at least one of
5 the active ingredients.
7. The composition as claimed in any of the preceding
claims for pharmaceutical or/and cosmetic
applications.
10
8. The composition as claimed in any of claims 1 to 1
as topical formulation.
9. The composition as claimed in claim 7 or 6 for use
15 in the hair.
10. The composition as claimed in claim 8 or 9,
characterised in that
the transdermal absorption of at least one of the
20 active ingredients is controllable.
11. The composition as claimed in any of the preceding
claims as solution, suspension, emulsion,
microemulsian, nanosystem, cream, gel, lotion,
25 spray, foam or ointment.
12. The composition as claimed in any of the preceding,
claims in a packaging or application system
selected from single-dose ampules made of plastics
30 or glass, tubes, bottles, spray bottles, patches,
sponges and textile or plastics carriers.
13. The composition as claimed in any of the preceding
claims for enhancing the hair follicle-stimulating
35 effect of melatonin through the addition of ginkgo
biloba and biotin.
14. The use of a composition as claimed in arty of the
preceding claims for promoting hair growth.

- 9 -
15. The use as claimed In claim 14 for producing an
agent for the prevention or/and treatment of
alopecia.
5
16. The use as claimed in claim 15 for the treatment
of alopecia in men.
17. The use as claimed in claim 15 for the treatment
10 of alopecia in women.
18. The use as claimed in any of claims 14 to 17,
characterised in that
from 0.001 mg to 10 mg of melatonin are
15 administered per application.
19. The use as claimed in claim 18,
characterized in that
from 0.01 mg to 1 mg of melatonin are administered
20 per application.

The present invention relates to a composition which
comprises as active ingredients a combination of
melatonin, ginkgo biloba and biotin. The composition is
particularly suitable for producing formulations for
topical application in the hair.

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Patent Number

216857

Indian Patent Application Number

01013/KOLNP/2005

PG Journal Number

12/2008

Publication Date

21-Mar-2008

Grant Date

19-Mar-2008

Date of Filing

30-May-2005

Name of Patentee

ASAT AG APPLIED SCIENCE & TECHNOLOGY

Applicant Address

GRIENBAHSTR. 17, 6300 ZUG,SWITZERLAND.

Inventors:

#	Inventor's Name	Inventor's Address
1	SCHMID,HANS,W.	REIDMATT 5,CH-6303 ZUG,SWITZERLAND.

PCT International Classification Number

A61P 17/14

PCT International Application Number

PCT/EP2003/012097

PCT International Filing date

2003-10-30

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	202 17 814.5	2002-11-18	Germany
2	102 50 646.9	2002-10-30	Germany
3	10/353,056	2003-01-29	Germany