Abstract: A composition for promoting hair sprouting and hair growth according to the present invention contains a higher content of ginsenoside Rb2 Rc and Rg1 and thus can provide better hair sprouting and hair growth effects compared to hair growth agents manufactured by existing techniques. Also the composition is made very safe by using plant based natural products and thus can be used as a skin preparation for external application for promoting hair sprouting and hair growth and can be widely used in cosmetic compositions pharmaceutical compositions and food compositions among others.
COMPOSITION FOR PROMOTING HAIR SPROUTING AND HAIR
GROWTH
5
【Technical Field】
The present disclosure relates to a composition for promoting hair sprouting
and hair growth, which contains a ginseng extract with increased ginsenoside
contents and promotes the growth of hair by accelerating transition from telogen to
10 anagen.
【Background Art】
Recently, due to increased social stress, environmental pollution,
Westernized eating habits such as convenience food, frequent hair perm and hair
15 dyeing, etc., those suffering from hair loss are increasing. Hair grows in cycles of
various phases: anagen is a hair growth phase; catagen is a phase where the growth
stops and the hair bulb withdraws; telogen is a phase where the dermal papilla stops
functioning and the hair remains on the scalp; and a morphogenesis phase is a phase
where the dermal papilla begins functioning or forms new hair and sheds old hair.
20 The anagen phase (2-7 years) where the hair grows is divided again into a
stage where the hair grows from a hair bulb to a hair follicle and a stage where hard
keratin is formed inside the hair follicle. The hair continues to grow until the catagen.
The catagen phase (2-3 weeks) is a phase where the anagen ends and the shape of
the hair is maintained as the metabolic process slows down. Keratin is not produced
2
in this phase. About 1% of the entire hair is in the catagen. During this phase, the
hair bulb withdraws and is divided to form a dermal papilla. It is shifted upward
being surrounded by the hair follicle and cell division is stopped. In the telogen
phase (3 months), the dermal papilla withdraws and the hair follicle shrinks gradually.
The hair falls as the hair root is shifted upward. It takes about 3-4 months 5 hs until the
next anagen phase begins.
Whereas normal people have much of their hair in the anagen phase, those
who suffer from hair loss (alopecia) have much of their hair in the telogen phase. As
hair loss proceeds, the anagen phase shortens and the hair becomes shorter.
10 Accordingly, to treat hair loss, it is important to accelerate transition of the hair follicle
in telogen phase to anagen and lengthen the anagen phase.
Male pattern hair loss occurs due to the male hormone called testosterone.
Testosterone is changed to dihydrotestosterone (DHT), which is a more potent
hormone, by the enzyme called 5α-reductase. This hormone acts on the hair follicle,
15 causing the hair follicle to transit from the anagen phase to the catagen phase,
thereby leading to hair loss. Therefore, inhibition of DHT synthesis by 5α-reductase
is a major target in the treatment of male pattern hair loss.
Female pattern hair loss occurs mainly after menopause due to decrease in
estrogen. For treatment of female pattern hair loss, minoxidil or estrogen is used
20 frequently.
Alopecia areata is an autoimmune disease caused by psychological stress or
genetic factors. Alopecia areata is fundamentally different from androgenic hair loss
in its cause and treatment method is also different. Adrenocortical hormone therapy,
application of minoxidil at the affected region or artificial stimulation of the affected
25 region is used.
3
Drugs that promote blood circulation, inhibit the action of male hormone,
strengthen hair root, etc. are commercially available for the purpose of relieving hair
loss. However, no one exhibits a clear effect and some have undesired side effects.
For example, minoxidil is sticky and is reported to cause skin irritation. Finasteride,
which is currently available for oral administration, is reported to have 5 side effects
such as sexual dysfunction. In addition, it is inconvenient to use because it has to
be taken orally.
[References of Related Art]
10 [Patent Documents]
Korean Patent Publication No. 10-2011-0000433.
【Disclosure】
【Technical Problem】
15 The present disclosure is directed to providing a ginseng extract with
increased ginsenoside contents and a composition for promoting hair sprouting and
hair growth with proven safety, which contains the same and promotes the growth of
hair by accelerating transition from telogen to anagen.
20 【Technical Solution】
In an aspect, the present disclosure provides a ginseng extract containing 2.5
wt% or more of ginsenoside Rb2, 3 wt% or more of ginsenoside Rc and 2 wt% or
more of ginsenoside Rg1 based on the total weight of the ginseng extract.
In another aspect, the present disclosure provides a ginseng extract which
4
further contains 6 wt% or more of ginsenoside Re.
In another aspect, the present disclosure provides a method for preparing the
ginseng extract, which includes:
a step of extracting ginseng by adding water, an organic solvent or a mixture
of water and an organic solvent and repeatedly applying and then reducing pressure5 ;
and
a step of preparing a ginseng extract by dissolving the resulting ginseng
extract in water, extracting with an organic solvent, removing the organic solvent layer
and then extracting the aqueous layer again with an organic solvent.
10 In another aspect, the present disclosure provides a composition for
promoting hair sprouting and hair growth, which contains the ginseng extract with
increased ginsenoside contents.
【Advantageous Effects】
15 A composition for promoting hair sprouting and hair growth according to the
present disclosure, which contains ginsenosides Rb2, Rc and Rg1 or Rb2, Rc, Rg1
and Re at increased concentrations, can exhibit a better effect of promoting hair
sprouting and hair growth than that of the existing hair growth stimulant.
Also, it exhibits superior safety because it uses a plant-derived natural product
20 and thus can be used as a composition for external application to skin for promoting
hair sprouting and hair growth. In addition, it can be widely used as a cosmetic
composition, a pharmaceutical composition, a food composition, etc.
【Brief Description of Drawings】
25 Fig. 1 shows the chemical structure of ginsenosides according to an
5
exemplary embodiment of the present disclosure.
Fig. 2 shows an HPLC analysis of ginsenosides contained in a ginseng
extract according to an exemplary embodiment of the present disclosure.
Fig. 3 shows an HPLC analysis of ginsenosides contained in a general
ginseng extract as a comparative exampl5 e.
Fig. 4 shows increased expression of VEGF as a hair growth factor in dermal
papilla cells by a ginseng extract according to an exemplary embodiment of the
present disclosure (Example 1) and a general ginseng extract as a comparative
example (Comparative Example 1).
10 Fig. 5 shows the effect of a ginseng extract according to an exemplary
embodiment of the present disclosure (Example 1) and a general ginseng extract as a
comparative example (Comparative Example 1) on proliferation of dermal papilla
cells (hDPc).
Fig. 6 shows the effect of ginsenosides contained in a ginseng extract
15 according to an exemplary embodiment of the present disclosure on proliferation of
dermal papilla cells (hDPc).
Fig. 7 shows the effect of a ginseng extract according to an exemplary
embodiment of the present disclosure (Example 1) and a general ginseng extract as a
comparative example (Comparative Example 1) on promotion of hair growth in
20 human hair follicle.
Fig. 8 shows the effect of a ginseng extract according to an exemplary
embodiment of the present disclosure (Example 1), a general ginseng extract as a
comparative example (Comparative Example 1) and ginsenosides Rb1, Rb2, Rc, Rd,
Re and Rg1 on promotion of hair growth in human hair follicle.
25
6
【Best Mode】
Hereinafter, the present disclosure is described in detail.
In an exemplary embodiment, the present disclosure provides a ginseng
extract containing 2.5 wt% or more of ginsenoside Rb2, 3 wt% or more of ginsenoside
Rc and 2 wt% or more of ginsenoside Rg1 based on the total weight of the ginsen5 g
extract.
In an exemplary embodiment, the present disclosure provides a ginseng
extract which further contains 6 wt% or more of ginsenoside Re.
Ginsenosides are a class of glycosides called saponins and are derived from
10 the root, stem, leaf, pericarp, seed, etc. of ginseng. There are various kinds of
ginsenosides, e.g., ginsenosides Rb1, Rb2, Rc, Rd, Re, Rg1, etc. The kinds and
contents of the ginsenoside existing in plants are different depending on the kind of
ginseng, cultivation condition, processing condition, extraction method, the part of
ginseng, etc. The chemical structure of different ginsenosides is shown in Fig. 1.
15 Ginsenosides can be classified into PPT (Re, Rg1) and PPD (Rb1, Rb2, Rc,
Rd) based on their structure. Ginsenosides Rb1, Rb2, Rc, Rd, Re and Rg1 are
ginsenosides existing in raw ginseng, without being processes to red ginseng, and
are water-soluble polar substances.
In another exemplary embodiment, the present disclosure provides a ginseng
20 extract obtained from the root of ginseng. Specifically, the present disclosure
provides a ginseng extract obtained from the rootlet of ginseng, which contains the
aforementioned ginsenosides at high concentrations.
In an exemplary embodiment, the present disclosure provides a ginseng
extract, which contains 2.5 wt% or more of ginsenoside Rb2, 3 wt% or more of
25 ginsenoside Rc, 6 wt% or more of ginsenoside Re and 2 wt% or more of ginsenoside
7
Rg1 based on the total weight of the ginseng extract. More specifically, the ginseng
extract may contain 2.5-4.5 wt% of ginsenoside Rb2, 3-7.5 wt% of ginsenoside Rc,
6-20 wt% of ginsenoside Re and 2-5 wt% of ginsenoside Rg1.
In an exemplary embodiment of the present disclosure, the ginseng extract
containing 2.5 wt% or more of ginsenoside Rb2, 3 wt% or more of ginsenoside 5 e Rc, 6
wt% or more of ginsenoside Re and 2 wt% or more of ginsenoside Rg1 based on the
total weight of the ginseng extract may be prepared by any method that enables
extraction of ginsenosides or other ingredients from ginseng. For example, it may
be prepared by pressure swing extraction of alternately applying and then reducing
10 pressure, solvent fractionation, etc. or by a combination of them in sequence.
Specifically, the pressure swing extraction may be performed by adding water, an
organic solvent or a mixture thereof to ginseng and applying and then reducing
pressure at given time intervals.
More specifically, in an exemplary embodiment of the present disclosure, the
15 ginseng extract containing ginsenosides Rb2, Rc and Rg1 at high concentrations can
be prepared as follows.
The ginseng extract may be prepared by a method including:
a step of extracting ginseng by adding water, an organic solvent or a mixture
of water and an organic solvent and repeatedly applying and then reducing pressure;
20 and
a step of preparing a ginseng extract by dissolving the resulting ginseng
extract in water, extracting with an organic solvent, removing the organic solvent layer
and then extracting the aqueous layer again with an organic solvent
The solvent that can be used in an exemplary embodiment of the present
25 disclosure is not particularly limited. For example, it may be water, an organic
8
solvent or a mixture of water and an organic solvent. For example, the organic
solvent may be one or more selected from a group consisting of ethanol, methanol,
butanol, ether, ethyl acetate and chloroform. For example, in the mixture solvent of
water and an organic solvent, the ratio of the organic solvent may be 10-90% (v/v).
More specifically, the extract may be obtained using 10-90% (v/v) ethanol, 5 , more
specifically 70% (v/v) ethanol, as a solvent.
In an exemplary embodiment of the present disclosure, the pressure swing
extraction may be performed by repeatedly applying and then reducing pressure
using a pressure swing extraction apparatus for 20-40 minutes each, over a total of
10 1.5-2.5 hours. In an exemplary embodiment of the present disclosure, the pressure
when applying the pressure may be 1-3 kgf/cm2 and the pressure when reducing the
pressure may be 550-650 mmHg. Extraction temperature may be 65-85 ºC.
When ginseng is extracted by repeatedly applying and then reducing pressure
as described above, thermal denaturation of ginseng can be minimized and, therefore,
15 denaturation of ginsenosides, e.g., glycolysis of ginsenoside Rb1 to Rg3, can be
minimized. As a result, extraction yield can be improved by 25-30% as compared to
when the extraction is performed using the existing simple extraction apparatus
without repetition. In addition, by removing nonpolar substances using an organic
solvent such as ethyl acetate and then extracting the aqueous layer using an organic
20 solvent such as butanol, the contents of ginsenosides can be maximized.
Specifically, according to this solvent fractionation method, the total contents of
ginsenosides in the ginseng extract can be improved from 1.5-2 wt% to 10 times or
more, specifically to 15-25 wt%.
In an exemplary embodiment, the present disclosure provides a composition
25 for promoting hair sprouting and hair growth, which contains the ginseng extract.
9
The composition exhibits remarkably superior effect of promoting the growth of hair
than one containing a general ginseng extract by accelerating transition from telogen
to anagen in the hair growth cycle. Accordingly, an unprecedented remarkable
effect of promoting hair sprouting and hair growth can be achieved.
In an exemplary embodiment, the present disclosure provides a use of 5 the
ginseng extract according to the present disclosure for promoting hair sprouting and
hair growth or a use of the composition containing the ginseng extract for promoting
hair sprouting and hair growth.
In another exemplary embodiment, the present disclosure provides a method
10 for promoting hair sprouting and hair growth, which includes administering an
effective amount of the ginseng extract according to the present disclosure as an
active ingredient to a subject. The ginseng extract may be administered being
contained in a composition.
In another exemplary embodiment, the present disclosure provides the
15 ginseng extract according to the present disclosure for use in promoting hair
sprouting and hair growth. The ginseng extract may be used being contained in a
composition.
In an exemplary embodiment of the present disclosure, the amount of the
ginseng extract containing ginsenosides Rb2, Rc and Rg1 contained in the
20 composition is not particularly limited. For example, it may be contained in an
amount of 2 wt% or more, for example, 2-20 wt%, based on the total weight of the
composition. When the ginseng extract is contained in an amount less than 2 wt%,
a sufficient effect of promoting hair growth cannot be expected. And, when it is
contained in an amount exceeding 20 wt%, there may be difficulties in terms of safety
25 or preparation.
10
For example, the composition according to an exemplary embodiment of the
present disclosure may be a pharmaceutical composition, a cosmetic composition or
a health food composition.
The pharmaceutical composition for promoting hair sprouting and hair growth
an exemplary embodiment of the present disclosure may further contain 5 a
pharmaceutical adjuvant such as an antiseptic, a stabilizer, a wetting agent, an
emulsifier, a salt and/or a buffer for control of osmotic pressure, etc. or other
therapeutically useful substance and may be prepared into various formulations for
oral or parenteral administration.
10 The formulation for oral administration includes, for example, a tablet, a pill, a
hard or soft capsule, a liquid, a suspension, an emulsifier, a syrup, a powder, a dust,
a fine granule, a granule, a pellet, etc. and may further contain, in addition to the
active ingredient, a surfactant, a diluent (e.g., lactose, dextrose, sucrose, mannitol,
sorbitol, cellulose and glycine) or a lubricant (e.g., silica, talc, stearic acid and its
15 magnesium or calcium salt and polyethylene glycol). The tablet may further contain
a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth,
methyl cellulose, sodium carboxymethyl cellulose and polyvinylpyrrolidone and may
further contain, if necessary, a pharmaceutical additive such as a disintegrant, e.g.,
starch, agar, alginic acid or its sodium salt, a humectant, a colorant, a flavor, a
20 sweetener, etc. The tablet may be prepared by a commonly employed mixing,
granulation or coating method. And, the formulation for parenteral administration
may be a formulation for transdermal administration. For example, it may be an
injection, a drop, an ointment, a lotion, a gel, a cream, a spray, a suspension, an
emulsion, a suppository, a patch, etc., although not being limited thereto.
25 The pharmaceutical composition according to an exemplary embodiment of
11
the present disclosure may be administered parenterally, e.g., rectally, topically,
transdermally, subcutaneously, etc. For example, the pharmaceutical composition
according to an exemplary embodiment of the present disclosure may be
administered topically to the scalp.
Determination of the administration dosage of the active ingredient is withi5 n
the level of those skilled in the art. A daily administration dosage varies depending
on various factors such as severity of related condition, progress of the condition, age,
physical condition, presence of complications(s), etc. For an adult, the composition
may be administered at a dosage of 1 μg/kg to 200 mg/kg, specifically 50 μg/kg to 50
10 mg/kg, 1-3 time(s) a day. However, the administration dosage does not limit the
scope of the present disclosure by any means.
The composition for promoting hair sprouting and hair growth according to an
exemplary embodiment of the present disclosure may be a cosmetic composition.
The cosmetic composition contains a cosmetically or dermatologically acceptable
15 medium or base. The composition may be provided in any topically applicable
formulation, e.g., a solution, a gel, a solid, an anhydrous paste, an oil-in-water
emulsion, a suspension, a microemulsion, a microcapsule, a microgranule, an ionic
(liposome) or nonionic vesicular dispersion, a cream, a skin lotion, a powder, an
ointment, a spray or a conceal stick. The composition may be prepared to according
20 a method commonly employed in the art. The composition according to the present
disclosure may be used in the form of a foam composition or an aerosol composition
further containing a compressed propellant.
The cosmetic composition according to an exemplary embodiment of the
present disclosure is not particularly limited in in formulation. For example, it may be
25 prepared into a cosmetic formulation such as a softening lotion, an astringent lotion, a
12
nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream,
an eye essence, a cleansing cream, a cleansing foam, a cleansing water, a pack, a
powder, a body lotion, a body cream, a body oil, a body essence, etc.
When the formulation of the cosmetic composition according to the present
disclosure is a paste, a cream or a gel, an animal oil, a plant oil, a wax, a paraffin, 5 a
starch, tragacanth, a cellulose derivative, polyethylene glycol, silicone, bentonite,
silica, talc, zinc oxide, etc. may be used as a carrier.
When the formulation of the cosmetic composition according to the present
disclosure is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium
10 silicate or polyamide powder may be used as a carrier. Especially, the spray may
further contain a propellant such as a chlorofluorohydrocarbon, propane/butane or
dimethyl ether.
When the formulation of the cosmetic composition according to the present
disclosure is a solution or an emulsion, a solvent, a solubilizer or an emulsifier may be
15 used as a carrier. Examples include water, ethanol, isopropanol, ethyl carbonate,
ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol,
a glycerol aliphatic ester, polyethylene glycol or a fatty acid ester of sorbitan.
When the formulation of the cosmetic composition according to the present
disclosure is a suspension, a liquid diluent such as water, ethanol or propylene glycol,
20 a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol
ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum
metahydroxide, bentonite, agar, tragacanth, etc. may be used as a carrier.
When the formulation of the cosmetic composition according to the present
disclosure is a surfactant-containing cleanser, an aliphatic alcohol sulfate, an aliphatic
25 alcohol ether sulfate, sulfosuccinic acid monoester, an isethionate, an imidazolinium
13
derivative, methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkyl
amidobetaine, an aliphatic alcohol, a fatty acid glyceride, a fatty acid diethanolamide,
a vegetable oil, a lanolin derivative, an ethoxylated glycerol fatty acid ester, etc. may
be used as a carrier.
In an exemplary embodiment of the present disclosure, the content 5 ent of the
active ingredient is not particularly limited. The composition may contain 0.001-20
wt% of the extract as the active ingredient based on the total weight of the
composition. A superior effect may be achieved without side effects when the above
content is satisfied.
10 The cosmetic composition according to an exemplary embodiment of the
present disclosure may further include, in addition to the extract as the active
ingredient, a functional additive and an ingredient usually contained in a cosmetic
composition. The functional additive may include an ingredient selected from a
group consisting of a water-soluble vitamin, an oil-soluble vitamin, a polypeptide, a
15 polysaccharide, a sphingolipid and a seaweed extract.
If necessary, the cosmetic composition according to an aspect of the present
disclosure may further contain an ingredient usually contained in a cosmetic
composition together with the functional additive. Such an ingredient may include
an oil, a fat, a humectant, an emollient, a surfactant, an organic or inorganic pigment,
20 an organic powder, a UV absorbent, an antiseptic, a sterilizer, an antioxidant, a plant
extract, a pH control agent, an alcohol, a colorant, a fragrance, a blood circulation
stimulant, a cooling agent, an antiperspirant, purified water, etc.
In addition, the composition according to an exemplary embodiment of the
present disclosure for promoting hair sprouting and hair growth may be a composition
25 for external application to skin. The composition for external application to skin is a
14
collective term including anything that can be applied on the skin from outside.
Cosmetics and drugs in various formulations may be included therein.
Also, the composition for promoting hair sprouting and hair growth according
to an exemplary embodiment of the present disclosure may be a health food
composition. Specifically, the health food composition of the present 5 ent disclosure may
contain 0.001-20 wt% of a ginseng extract containing ginsenosides Rb2, Rc, Re and
Rg1 as active ingredients based on the total weight of the composition. When the
content of the extract is less than 0.001 wt%, the desired effect may not achieved
sufficiently. And, when it exceeds 20 wt%, the efficiency of the addition of the active
10 ingredient may decrease.
The health food composition according to an exemplary embodiment of the
present disclosure may be prepared into a liquid or solid formulation such as a tablet,
a capsule, a soft capsule, a pill, a granule, a drink, a diet bar, a chocolate, a caramel,
confectionery, etc., but is not particularly limited in formulation. The health food
15 composition of the present disclosure may further contain, in addition to the active
ingredient, an excipient, a sugar, a fragrance, a colorant, an oil, a fat, a protein, etc., if
necessary.
【Mode for Invention】
20 Hereinafter, the present disclosure will be described in detail through
examples and test examples. However, the following examples and test examples
are for illustrative purposes only and the scope of the present disclosure is not limited
by them.
Also, it will be obvious to those of ordinary skill in the art that various changes
25 and modifications can be made without departing from the scope of the present
15
disclosure defined in the appended claims.
[Example 1] Preparation of ginseng extract containing ginsenosides Rb2, Rc,
Rg1 and Re at increased concentrations
Ginseng (Geumsan ginseng, acquired from Geumsaninsam Nonghyup) 5 ) was
washed with purified water, dried and then pulverized into fine powder. 2 g of the
obtained ginseng powder was added to 20 mL of 50% ethanol and then extracted for
a total of 2 hours by repeatedly applying and then reducing pressure using a pressure
swing extraction apparatus for 30 minutes each using a pressure swing extraction
10 apparatus. The pressure when applying the pressure was 2 kgf/cm2 and the
pressure when reducing the pressure was 600 ± 50 mmHg. Extraction temperature
was set to 75 ºC. The ginseng extract obtained from the pressure swing extraction
process was filtered and a supernatant was dried under reduced pressure. The
resulting dried product (dry weight = 0.57 g) was dissolved in water and extracted with
15 ethyl acetate. After removing the ethyl acetate layer, the aqueous layer was
extracted with butanol and then dried under reduced pressure (dry weight = 2.7 g).
Ginsenosides contained in the ginseng extract of Example 1 were analyzed
by HPLC using the following analysis instrument and analysis condition. Based on
the result, the content of each ginsenoside ingredient contained in the extract was
20 calculated in wt% unit. The result is shown in Table 2 and Fig. 2.
HPLC analysis instrument and analysis condition
Instrument: Waters 2998 PDA detector, 1525 pump, 2707 autosampler.
Column: Sun fire C18 305 μm, 4.6 x 150 mm.
Detector: UV 203 nm.
25 Flow rate: 1 mL/min.
16
Injection volume: 20 μL.
Condition: gradient (A: water, B: acetonitrile).
【Table 1】
Time (min) A (water) B (acetonitrile)
0 82 18
22 82 18
32 70 30
60 50 50
【Table 2】
Ginseng extract
(Example 1)
Content (%)
Rg1 Re Rb1 Rc Rb2 Rd
2.1 6.23 3.52 3.14 2.91 1.58
As seen from Table 2 and Fig. 2, the ginseng extract of Example 1 accordin5 g
to the present disclosure contained 2.91 wt% (i.e., 2.5 wt% or more) of ginsenoside
Rb2, 3.14 wt% (i.e., 3 wt% or more) of ginsenoside Rc, 6.23 wt% (i.e., 6 wt% or more)
of ginsenoside Re and 2.1 wt% (i.e., 2.0 wt% or more) of ginsenoside Rg1.
10 [Comparative Example 1] Preparation of general ginseng extract
Ginseng (Geumsan ginseng, acquired from Geumsaninsam Nonghyup) was
washed with purified water, dried and then pulverized into fine powder. 2 g of the
obtained ginseng powder was extracted with 100 mL of 50% ethanol at 75 ºC for 2
hours. After filtering, a supernatant was dried under reduced pressure (dry weight =
15 0.30 g).
17
Ginsenosides contained in the ginseng extract of Comparative Example 1
were analyzed by HPLC using the same analysis instrument and analysis condition
as in Example 1. Based on the result, the content of each ginsenoside ingredient
contained in the extract was calculated in wt% unit. The result is shown in Table 3
and Fig. 5 3.
【Table 3】
Ginseng extract
(Comparative
Example 1)
Content (%)
Rg1 Re Rb1 Rc Rb2 Rd
0.14 0.16 0.67 0.55 0.33 0.13
As seen from Table 3 and Fig. 3, the ginseng extract of Comparative Example
1 contained 0.33 wt% of ginsenoside Rb2, 0.55 wt% of ginsenoside Rc, 0.16 wt% of
ginsenoside Re and 0.14 wt% of ginsenoside Rg1. Therefore, it was confirmed that
10 the ginseng extract of Example 1 according to the present disclosure contains 5-15
times more of each ginsenoside than the general ginseng extract. Also, it was
confirmed that the total weight of the ginsenosides contained in the ginseng extract is
much greater for Example 1 according to the present disclosure than for Comparative
Example 1.
15
[Test Example 1] Evaluation of expression of hair growth factor VEGF in
dermal papilla cells
The expression of the vascular endothelial growth factor (VEGF) which is a
growth factor necessary for blood vessel formation for transition to the anagen phase
20 of the hair cycle was evaluated after application of the ginseng extract using an
in-vitro system.
18
4x105 dermal papilla cells (DPC) (P.11) of a 47-year-old male adult were
seeded onto a 12-well plate and cultured overnight in Dulbecco's modified Eagle's
medium (DMEM) containing 10% fetal bovine serum (FBS). Then, the cells were
treated with 20 ppm of the ginseng extract of Example 1 or Comparative Example 1.
DMSO was used for a negative control group. 24 hours later, the cell culture 5 e treated
with the extract of Example 1 or Comparative Example 1 was soup collected and the
expression level of VEGF was investigated using the VEGF ELISA kit (vascular
endothelial growth factor enzyme-linked immunosorbent assay; R&D Biosystems).
The result is shown in Fig. 4.
10 As seen from Fig. 4, the general ginseng extract of Comparative Example 1
showed no significant difference from the control group not treated with a ginseng
extract. In contrast, the ginseng extract of Example 1 according to the present
disclosure increased the expression of the hair growth factor VEGF in the dermal
papilla cells about 3 times at the same concentration of the ginseng extract of
15 Comparative Example 1. That is to say, the ginseng extract of Example 1 which
contains ginsenosides Rb2, Rc, Rg1, etc. in larger quantities than the general
ginseng extract of Comparative Example 1 effectively increased the expression of the
hair growth factor VEGF in the dermal papilla cells. Accordingly, it was confirmed
that the ginseng extract according to the present disclosure has a superior effect of
20 promoting hair sprouting.
[Test Example 2] Evaluation of proliferation of dermal papilla cells
The protein keratin which constitutes hair is produced by keratinocytes at the
hair root and the keratinocytes are differentiated from dermal papilla cells.
25 Accordingly, if that the ginseng extract according to the present disclosure can
19
promote the activity of dermal papilla cells, it will be able to promote the activity of the
keratinocytes differentiated therefrom and can promote hair sprouting.
Therefore, the effect of the ginseng extract on the promotion of the activity of
the dermal papilla cells was evaluated as follows.
A human dermal papilla cell line was used for the experiment. The cell 5 line
was cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco BRL,
Gaithersburg, MD, USA) containing 10% fetal bovine serum (FBS) for 24 hours in an
incubator maintained at 5% CO2 and 37 ºC and then treated with the ginseng extract
of Example 1 at 10 ppm or 20 ppm or with the ginseng extract of Comparative
10 Example 1 at 20 ppm. DMSO was used for a negative control group. 24 hours
after the treatment with the test substance, cell proliferation (%) was measured using
the WST-1 kit (Roche). The result is shown in Fig. 5.
As seen from Fig. 5, the ginseng extract of Example 1 according to the
present disclosure significantly increased the proliferation of the cells at 10 ppm and
15 20 ppm. In particular, the proliferation of the dermal papilla cells was increased by
about 1.5 times when they were treated with the ginseng extract of Example 1 at 10
ppm than when the cells were treated with the general ginseng extract of
Comparative Example 1 at 20 ppm. The fact that the ginseng extract according to
the present disclosure can promote the proliferation of the dermal papilla cells better
20 than the existing general ginseng extract means that it can more effectively promote
the activity of keratinocytes and hair sprouting.
[Test Example 3] Evaluation of hair growth promoting effect using human hair
follicle
25 The hair growth promoting effect of the ginseng extract of the present
20
disclosure was evaluated using the human hair follicle.
First, dermal papilla cells were treated with each of ginsenosides Rb1, Rb2,
Rc, Rd, Re and Rg1, which are major ingredients of the ginseng extract, at 0.1 μM or
1 μM in the same manner as in Test Example 2. 24 hours later, cell proliferation (%)
was measured using the WST-1 kit (Roche). The result is shown in Fig. 65 .
Then, hair follicles were separated one by one from the scalp tissue at the
occipital region of a 55-year-old male adult and cultured in William’s medium (2 mM
L-glutamine, 10 μg/mL insulin, 40 ng/mL hydrocortisone, 1% antibiotic, 1% antifungal
agent). 3 days later, the hair follicle tissues that had grown were cut to a size of 3
10 mm and then treated with nothing (control), with the ginseng extract of Example 1 at 2
ppm or 5 ppm or with the ginseng extract of Comparative Example 1 at 5 ppm. 8
days after the treatment, the hair follicle tissues were measured and photographed.
Also, in the same manner as described above, hair follicle tissues were treated with
each of ginsenosides Rb1, Rb2, Rc, Rd, Re and Rg1, the ginseng extract of
15 Comparative Example 1 and the ginseng extract of Example 1 at 5 ppm. The result
is shown in Fig. 7 and Fig. 8.
As seen from Fig. 6, ginsenosides Rb1, Rc and Rg1 showed distinct and
statistically significant hair growth promoting effect among the ginsenosides.
Also, as seen from Fig. 7, the hair follicle tissues treated with the ginseng
20 extract of Example 1 at 5 ppm showed superior hair growth promoting effect in terms
of increased hair length than the ginseng extract of Comparative Example 1 or the
control. In particular, Comparative Example 1 showed smaller average growth
length than the control group. As seen from Fig. 8, although the ginsenosides Rb1,
Rb2, Rc, Rd, Re and Rg1 also led to larger average growth length than Comparative
25 Example 1, Example 1 showed the longest average growth length.
21
Accordingly, from the results of Fig. 6, Fig. 7 and Fig. 8, it can be seen that the
ginseng extract according to the present disclosure provides superior effect of
promoting hair growth in hair follicles because it contains the ginsenosides Rb1, Rc
and Rg1 having hair growth promoting effect at increased concentrations as
compared to the existing general ginseng ex5 tract.
[Test Example 4] Clinical test on patients with hair loss
Female adults aged between 20 and 60 with hair loss were divided into a test
group (Example 1) and a control group, with 23 people each. Each group was asked
10 to apply a scalp essence containing 2% of the ginseng extract of Example 1 or a
control scalp essence not containing the extract on the depilated area once a day in
the evening. For 16 weeks, the effect on prevention of hair loss and promotion of
hair growth was evaluated subjectively by the test subjects, objectively by a
researcher based on photographs and using phototrichograms as a non-invasive hair
15 evaluation method with hair density, hair thickness, hair growth speed and number of
shedding hairs as biological variables. The test was designed as a randomized,
double-blind, comparative clinical study. The result is shown in Tables 4-8.
The hair density of Example 1 and the control group was compared in Table 4.
For Example 1, the hair density increased significantly by 5.485% and 7.409% at 8
20 and 16 weeks, respectively. The ratio of subjects who experienced improvement
was 86.364% and 86.364% at 8 and 16 weeks, respectively. In contrast, for the
control group, the hair density increased by 1.615% and 1.334% at 8 and 16 weeks,
respectively.
The hair growth speed of Example 1 and the control group was compared in
25 Table 4. For Example 1, the hair growth speed increased significantly by 3.218%
22
and 8.783% at 8 and 16 weeks, respectively. The ratio of subjects who experienced
improvement was 68.182% and 81.818% at 8 and 16 weeks, respectively. In
contrast, for the control group, the hair growth speed increased by 2.480% and
decreased by 1.142% at 8 and 16 weeks, respectively.
【Table 5 4】
Mean ± STDEV Improvemen
t (%)
Ratio of
subjects who
experienced
improvement
(%)
Significant
difference vs.
before use (p
value)
Significant
difference vs.
control (p
value)
Exampl
e 1 Before 8
weeks
16
weeks
8
week
s
16
weeks
8
weeks
16
weeks
8
week
s
16 weeks 8 weeks
16
week
s
Density
(n/cm2)
111.04
5 ±
20.285
117.13
6 ±
19.833
119.27
3 ±
19.452
5.485 7.409 86.364 86.364 0.000
* 0.000*
0.008
#
0.00
1#
Growth
speed
(μm/day
)
0.292
±
0.056
0.301
±
0.080
0.318
±
0.044
3.218 8.783 68.182 81.818 0.098 0.004* 0.496 0.02
5**
Control Before 8
weeks
16
weeks
8
week
s
16
weeks
8
weeks
16
weeks
8
week
s
16 weeks 8 weeks
16
week
s
Density
(n/cm2)
123.82
6 ±
18.968
125.82
6 ±
23.796
125.47
8 ±
25.293
1.615 1.334 47.826 43.478 0.267 0.444 N.A N.A
Growth
speed
(μm/day
)
0.289
±
0.047
0.297
±
0.042
0.286
±
0.046
2.480 -1.142 50.000 45.455 0.471 0.732 N.A N.A
*: Paired samples t-test, p < 0.05.
**: Independent samples t-test, p < 0.05.
23
#: Mann-Whitney U test, p < 0.05.
The hair thickness of Example 1 and the control group was compared in Table
5. For Example 1, the hair thickness increased significantly by 1.526%, 2.611%,
4.782% and 7.178 % at 2, 4, 8 and 16 weeks, respectively. The ratio of subjects
who experienced improvement was 72.727%, 81.818%, 95.455% and 95.455% at 5 2,
4, 8 and 16 weeks, respectively. In contrast, for the control group, the hair thickness
decreased by 0.903%, 0.765%, 0.595% and 1.084% at 2, 4, 8 and 16 weeks,
respectively.
【Table 5】
Mean ± STDEV Improvement (%)
Ratio of subjects
who experienced
improvement (%)
Significant
difference vs.
before use (p
value)
Significa
nt
differenc
e vs.
control
(p value)
Thickness
(μm) Example 1 Control Example 1 Control Example 1 Control Example
1
Contro
l
Before 0.080 ±
0.010
0.082 ±
0.011 N.A N.A N.A N.A N.A N.A N.A
2 weeks 0.082 ±
0.011
0.081 ±
0.011 1.526 -0.903 72.727 34.783 0.021† 0.084 0.002#
4 weeks 0.083 ±
0.011
0.081 ±
0.010 2.611 -0.765 81.818 52.174 0.001† 0.235 0.001#
8 weeks 0.084 ±
0.012
0.081 ±
0.011 4.782 -0.595 95.455 43.478 0.000† 0.134 0.000#
16 weeks 0.086 ±
0.012
0.081 ±
0.010 7.178 -1.084 95.455 52.174 0.000* 0.218 0.000#
10 *: Paired samples t-test, p < 0.05.
†: Wilcoxon signed rank test, p < 0.05.
#: Mann-Whitney U test, p < 0.05.
The number of shedding hairs of Example 1 and the control group was
compared in Table 6. For Example 1, the number of shedding hairs increased by
15 1.589% at 4 weeks, decreased by 4.849% at 8 weeks and decreased by 33.278% at
16 weeks. The decrease at 16 weeks was significant. The ratio of subjects who
experienced improvement was 50.000%, 54.545% and 72.727% at 4, 8 and 16
24
weeks, respectively. In contrast, for the control group, the number of shedding hairs
increased by 26.721% at 4 weeks, decreased by 1.953% at 8 weeks and increased
by 2.364% at 16 weeks.
【Table 6】
Mean ± STDEV
Improvement
(%)
Ratio of
subjects who
experienced
improvement
(%)
Significant
difference vs.
before use (p
value)
Significa
nt
differenc
e vs.
control (p
value)
Number
of
shedding
hairs
(ea)
Example 1 Control
Example
1
Control
Example
1
Control
Example
1
Control
Before
54.364 ±
29.589
42.304 ±
20.328
N.A N.A N.A N.A N.A N.A N.A
4 weeks
55.227 ±
28.846
53.609 ±
38.577
1.589 26.721 50.000 43.478 0.903 0.102 0.452
8 weeks
51.727 ±
36.482
41.478 ±
25.472
-4.849 -1.953 54.545 43.478 0.733 0.870 0.776
16 weeks
36.273 ±
23.511
43.304 ±
34.189
-33.278 2.364 72.727 52.174 0.006* 0.833 0.047**
25
*: Paired samples t-test, p < 0.05.
**: Independent samples t-test, p < 0.05.
The result of visual evaluation of hair loss improvement of Example 1 and the
control group was compared in Table 7. For Example 1, the hair loss improvement
score increased by 0.045, 0.318 and 0.364 at 4, 8 and 16 weeks, respectively. Th5 e
improvement at 8 and 16 weeks was significant. The ratio of subjects who
experienced improvement was 9.091%, 22.727% and 36.364% at 4, 8 and 16 weeks,
respectively. In contrast, for the control group, the hair loss improvement score
decreased by 0.130, increased by 0.087 and decreased by 0.087 at 4, 8 and 16
10 weeks, respectively. The ratio of subjects who experienced improvement was
0.000%, 17.391% and 17.39% at 4, 8 and 16 weeks, respectively.
【Table 7】
Mean ± STDEV
Ratio of subjects who
experienced
improvement (%)
Significant difference
vs. before use (p
value)
Significant
difference vs.
control (p
value)
Hair loss
improvement
(score)
Example 1 Control Example 1 Control Example 1 Control
Before
0.000 ±
0.000
0.000 ±
0.000
N.A N.A N.A N.A N.A
4 weeks
0.045 ±
0.375
-0.130 ±
0.344
9.091 0.000 0.564 0.083 0.110
8 weeks
0.318 ±
0.646
0.087 ±
0.515
22.727 17.391 0.038† 0.414 0.297
26
16 weeks
0.364 ±
0.790
-0.087 ±
0.848
36.364 17.391 0.046† 0.627 0.070
†: Wilcoxon signed rank test, p < 0.05.
※ Visual evaluation of hair loss improvement: improved greatly (3), improved (2), improved slightly (1),
no difference (0), worsened slightly (-1), worsened (-2), worsened greatly (-3).
※ Improvement rate cannot be calculated because score of hair loss improvement before use is 0.
Thus, ratio of subjects who experienced improvement is evaluated rather than improvement rate5 .
The result of subjective evaluation of improvement by the subjects of Example
1 and the control group was compared in Table 8. For Example 1, 40.9% and 63.6%
of the subjects responded positively at 8 and 16 weeks, respectively, and only 0.0%
10 and 4.4% responded negatively at 8 and 16 weeks, respectively. For the control
group, 52.1% and 39.1% of the subjects responded positively at 8 and 16 weeks,
respectively, and 0.0% and 8.7% responded negatively at 8 and 16 weeks,
respectively.
【Table 8】
Mean ± STDEV
Positive response
(%)
Negative response
(%)
Significant
difference vs.
control (p value)
Example 1 8 weeks 16 weeks 8 weeks 16 weeks 8 weeks 16 weeks 8 weeks 16 weeks
Hair loss
improvement
(score)
2.455 ±
0.596
2.727 ±
0.767
40.909 63.636 0.000 4.545 0.486 0.087
Control 8 weeks 16 weeks 8 weeks 16 weeks 8 weeks 16 weeks 8 weeks 16 weeks
27
Hair loss
improvement
(score)
2.565 ±
0.590
2.348 ±
0.714
52.174 39.130 0.000 8.696 N.A N.A
※ Subjective evaluation of improvement by subjects: very good (4), good (3), moderate (2), poor (1),
very poor (0).
※ Positive response (%): ratio of subjects who responded very good (4) or good (3).
※ Negative response (%): ratio of subjects who responded poor (1) or very poor (0).
To conclude, the ginseng extract of Example 1 according to the pr5 esent
disclosure exhibited excellent effect of preventing hair loss and promoting hair growth
with application only once a day.
Hereinafter, the present disclosure will be described in detail through
10 formulation examples. However, the following examples are for illustrative purposes
only and the scope of the present disclosure is not limited by them.
[Formulation Example 1] Shampoo as formulation for external application to
skin
15 A shampoo was prepared according to a commonly employed method with
the composition described in Table 9.
【Table 9】
Ingredients Contents (wt%)
Extract of Example 1 2.00
Sodium lauryl sulfate 10.00
Cocamidopropyl betaine 3.00
28
Carboxyvinyl polymer 0.30
Polyquaternium-10 0.20
Cetyl trimethyl ammonium chloride 0.10
Purified water balance
Total 100.00
[Formulation Example 2] Rinse as formulation for external application to skin
A rinse was prepared according to a commonly employed method with the
composition described in Table 10.
【Table 5 10】
Ingredients Contents (wt%)
Extract of Example 1 2.00
Cetyl alcohol 2.00
Stearyl alcohol 2.50
Behenyl alcohol 0.50
Silicone emulsion 0.40
Cyclomethicone 1.00
Dimethyl stearyl ammonium chloride 0.10
Purified water balance
Total 100.00
29
[Formulation Example 3] Ointment as formulation for external application to
skin
An ointment was prepared according to a commonly employed method with
the composition described in Table 11.
【Table 5 11】
Ingredients Contents (wt%)
Extract of Example 1 2.00
Glycerin 8.00
Butylene glycol 4.00
Liquid paraffin 15.00
β-Glucan 7.00
Carbomer 0.10
Caprylic/capric triglyceride 3.00
Squalane 1.00
Cetearyl glucoside 1.50
Sorbitan stearate 0.40
Cetearyl alcohol 1.00
Beeswax 4.00
Purified water balance
Total 100.00
[Formulation Example 4] Lotion
30
A lotion was prepared according to a commonly employed method with the
composition described in Table 12.
【Table 12】
Ingredients Contents (wt%)
Extract of Example 1 2.00
L-Ascorbic acid 2-phosphate magnesium salt 1.00
Water-soluble collagen (1% aqueous solution) 1.00
Sodium citrate 0.10
Citric acid 0.05
Licorice extract 0.20
1,3-Butylene glycol 3.00
Purified water balance
Total 100.00
[Formulation Example 5] Crea5 m
A cream was prepared according to a commonly employed method with the
composition described in Table 13.
【Table 13】
Ingredients Contents (wt%)
Extract of Example 1 2.00
Polyethylene glycol monostearate 2.00
Self-emulsifying glyceryl monostearate 5.00
31
Cetyl alcohol 4.00
Squalane 6.00
Glyceryl tri(2-ethylhexanoate) 6.00
Sphingoglycolipid 1.00
1,3-Butylene glycol 7.00
Purified water balance
Total 100.00
[Formulation Example 6] Pack
A pack was prepared according to a commonly employed method with the
composition described in Table 14.
【Table 5 14】
Ingredients Contents (wt%)
Extract of Example 1 2.00
Polyvinyl alcohol 13.00
L-Ascorbic acid 2-phosphate magnesium salt 1.00
Lauroyl hydroxyproline 1.00
Water-soluble collagen (1% aqueous solution) 2.00
1,3-Butylene glycol 3.00
Ethanol 5.00
Purified water balance
32
Total 100.00
[Formulation Example 7] Beauty care solution
A beauty care solution was prepared according to a commonly employed
method with the composition described in Table 15.
【Table 5 15】
Ingredients Contents (wt%)
Extract of Example 1 2.00
Hydroxyethylene cellulose (2% aqueous solution) 12.00
Xanthan gum (2% aqueous solution) 2.00
1,3-Butylene glycol 6.00
Thick glycerin 4.00
Sodium hyaluronate (1% aqueous solution) 5.00 5.00
Purified water balance
Total 100.00
[Formulation Example 8] Soft capsule
A soft capsule was prepared according to a commonly employed method by
mixing 50 mg of the extract of Example 1, 80-140 mg of L-carnitine, 180 mg of
10 soybean oil, 2 mg of palm oil, 8 mg of hydrogenated vegetable oil, 4 mg of yellow
beeswax and 6 mg of lecithin and filling 400 mg of the mixture in a capsule.
33
[Formulation Example 9] Tablet
50 mg of the extract of Example 1, 200 mg of galactooligosaccharide, 60 mg
of lactose and 140 mg of maltose were mixed and granulated using a fluidized-bed
drier. After adding 6 mg of sugar ester, the granule was prepared into a table using
a tablet making machine5 .
[Formulation Example 10] Granule
50 mg of the extract of Example 1, 250 mg of anhydrous crystalline glucose
and 550 mg of starch were mixed and granulated using a fluidized-bed drier. The
10 resulting granule was filled in a pouch.
[Formulation Example 11] Drink
50 mg of the extract of Example 1, 10 g of glucose, 0.6 g of citric acid and 25 g
of oligosaccharide syrup were mixed. After adding 300 mL of purified water, 200 mL
15 of the mixture was filled in a bottle. The resulting drink was sterilized at 130 ºC for
4-5 seconds.
34
【CLAIMS】
【Claim 1】
A ginseng extract comprising 2.5 wt% or more of ginsenoside Rb2, 3 wt% or
more of ginsenoside Rc and 2 wt% or more of ginsenoside Rg1 based on the total
weight of the ginseng extract5 .
【Claim 2】
The ginseng extract according to claim 1, wherein the ginseng extract further
comprises 6 wt% or more of ginsenoside Re based on the total weight of the ginseng
10 extract.
【Claim 3】
The ginseng extract according to claim 1, wherein the ginseng extract is one
obtained from the root of ginseng.
15
【Claim 4】
The ginseng extract according to claim 1, wherein the ginseng extract is one
obtained from the rootlet of ginseng.
20 【Claim 5】
A method for preparing the ginseng extract according to claim 1, which
comprises:
a step of extracting ginseng by adding water, an organic solvent or a mixture
of water and an organic solvent and repeatedly applying and then reducing pressure;
35
and
a step of preparing a ginseng extract by dissolving the resulting ginseng
extract in water, extracting with an organic solvent, removing the organic solvent layer
and then extracting the aqueous layer again with an organic solvent
5 .
【Claim 6】
A ginseng extract prepared by the method according to claim 5.
10 【Claim 7】
A composition for promoting hair sprouting and hair growth, which comprises
the ginseng extract according to any of claims 1 to 4 as an active ingredient.
【Claim 8】
15 The composition for promoting hair sprouting and hair growth according to
claim 7, which comprises 2 wt% or more of the ginseng extract based on the total
weight of the composition.
【Claim 9】
20 The composition for promoting hair sprouting and hair growth according to
claim 7, wherein the ginsenosides contained in the ginseng extract accelerates
transition from telogen to anagen in the hair growth cycle.
36
【Claim 10】
The composition for promoting hair sprouting and hair growth according to
claim 7, wherein the composition is a pharmaceutical composition.
【Claim 115 】
The composition for promoting hair sprouting and hair growth according to
claim 7, wherein the composition is a cosmetic composition.
【Claim 12】
10 The composition for promoting hair sprouting and hair growth according to
claim 7, wherein the composition is a composition for external application to skin.
【Claim 13】
The composition for promoting hair sprouting and hair growth according to
15 claim 7, wherein the composition is a food composition.
| Section | Controller | Decision Date |
|---|---|---|
| 15 | ANITA JATAV | 2022-11-11 |
| 15 | ANITA JATAV | 2022-11-15 |
| # | Name | Date |
|---|---|---|
| 1 | 201617003890-IntimationOfGrant15-11-2022.pdf | 2022-11-15 |
| 1 | Priority Document [03-02-2016(online)].pdf | 2016-02-03 |
| 2 | 201617003890-PatentCertificate15-11-2022.pdf | 2022-11-15 |
| 2 | Form 5 [03-02-2016(online)].pdf | 2016-02-03 |
| 3 | Form 3 [03-02-2016(online)].pdf | 2016-02-03 |
| 3 | 201617003890-Written submissions and relevant documents [14-10-2022(online)].pdf | 2022-10-14 |
| 4 | Drawing [03-02-2016(online)].pdf | 2016-02-03 |
| 4 | 201617003890-Correspondence to notify the Controller [23-09-2022(online)].pdf | 2022-09-23 |
| 5 | Description(Complete) [03-02-2016(online)].pdf | 2016-02-03 |
| 5 | 201617003890-US(14)-HearingNotice-(HearingDate-04-10-2022).pdf | 2022-08-30 |
| 6 | 201617003890-GPA-(11-03-2016).pdf | 2016-03-11 |
| 6 | 201617003890-FER.pdf | 2021-10-17 |
| 7 | 201617003890-Form-1-(11-03-2016).pdf | 2016-03-11 |
| 7 | 201617003890-FORM 3 [10-06-2021(online)].pdf | 2021-06-10 |
| 8 | 201617003890-Correspondecne Others-(11-03-2016).pdf | 2016-03-11 |
| 8 | 201617003890-ABSTRACT [14-10-2020(online)].pdf | 2020-10-14 |
| 9 | 201617003890-CLAIMS [14-10-2020(online)].pdf | 2020-10-14 |
| 9 | 201617003890.pdf | 2016-06-06 |
| 10 | 201617003890-CORRESPONDENCE [14-10-2020(online)].pdf | 2020-10-14 |
| 10 | abstract.jpg | 2016-06-29 |
| 11 | 201617003890-DRAWING [14-10-2020(online)].pdf | 2020-10-14 |
| 11 | Form 3 [16-07-2016(online)].pdf | 2016-07-16 |
| 12 | 201617003890-FER_SER_REPLY [14-10-2020(online)].pdf | 2020-10-14 |
| 12 | Form 3 [11-01-2017(online)].pdf | 2017-01-11 |
| 13 | 201617003890-OTHERS [14-10-2020(online)].pdf | 2020-10-14 |
| 13 | Form 18 [09-06-2017(online)].pdf | 2017-06-09 |
| 14 | 201617003890-FORM 3 [09-10-2020(online)].pdf | 2020-10-09 |
| 14 | Form 3 [07-07-2017(online)].pdf | 2017-07-07 |
| 15 | 201617003890-FORM 3 [10-01-2018(online)].pdf | 2018-01-10 |
| 15 | 201617003890-Information under section 8(2) [09-10-2020(online)].pdf | 2020-10-09 |
| 16 | 201617003890-FORM 3 [23-12-2019(online)].pdf | 2019-12-23 |
| 16 | 201617003890-FORM 3 [26-06-2018(online)].pdf | 2018-06-26 |
| 17 | 201617003890-FORM 3 [14-12-2018(online)].pdf | 2018-12-14 |
| 17 | 201617003890-FORM 3 [12-06-2019(online)].pdf | 2019-06-12 |
| 18 | 201617003890-FORM 3 [12-06-2019(online)].pdf | 2019-06-12 |
| 18 | 201617003890-FORM 3 [14-12-2018(online)].pdf | 2018-12-14 |
| 19 | 201617003890-FORM 3 [23-12-2019(online)].pdf | 2019-12-23 |
| 19 | 201617003890-FORM 3 [26-06-2018(online)].pdf | 2018-06-26 |
| 20 | 201617003890-FORM 3 [10-01-2018(online)].pdf | 2018-01-10 |
| 20 | 201617003890-Information under section 8(2) [09-10-2020(online)].pdf | 2020-10-09 |
| 21 | 201617003890-FORM 3 [09-10-2020(online)].pdf | 2020-10-09 |
| 21 | Form 3 [07-07-2017(online)].pdf | 2017-07-07 |
| 22 | 201617003890-OTHERS [14-10-2020(online)].pdf | 2020-10-14 |
| 22 | Form 18 [09-06-2017(online)].pdf | 2017-06-09 |
| 23 | 201617003890-FER_SER_REPLY [14-10-2020(online)].pdf | 2020-10-14 |
| 23 | Form 3 [11-01-2017(online)].pdf | 2017-01-11 |
| 24 | Form 3 [16-07-2016(online)].pdf | 2016-07-16 |
| 24 | 201617003890-DRAWING [14-10-2020(online)].pdf | 2020-10-14 |
| 25 | 201617003890-CORRESPONDENCE [14-10-2020(online)].pdf | 2020-10-14 |
| 25 | abstract.jpg | 2016-06-29 |
| 26 | 201617003890-CLAIMS [14-10-2020(online)].pdf | 2020-10-14 |
| 26 | 201617003890.pdf | 2016-06-06 |
| 27 | 201617003890-ABSTRACT [14-10-2020(online)].pdf | 2020-10-14 |
| 27 | 201617003890-Correspondecne Others-(11-03-2016).pdf | 2016-03-11 |
| 28 | 201617003890-FORM 3 [10-06-2021(online)].pdf | 2021-06-10 |
| 28 | 201617003890-Form-1-(11-03-2016).pdf | 2016-03-11 |
| 29 | 201617003890-FER.pdf | 2021-10-17 |
| 29 | 201617003890-GPA-(11-03-2016).pdf | 2016-03-11 |
| 30 | 201617003890-US(14)-HearingNotice-(HearingDate-04-10-2022).pdf | 2022-08-30 |
| 30 | Description(Complete) [03-02-2016(online)].pdf | 2016-02-03 |
| 31 | Drawing [03-02-2016(online)].pdf | 2016-02-03 |
| 31 | 201617003890-Correspondence to notify the Controller [23-09-2022(online)].pdf | 2022-09-23 |
| 32 | Form 3 [03-02-2016(online)].pdf | 2016-02-03 |
| 32 | 201617003890-Written submissions and relevant documents [14-10-2022(online)].pdf | 2022-10-14 |
| 33 | Form 5 [03-02-2016(online)].pdf | 2016-02-03 |
| 33 | 201617003890-PatentCertificate15-11-2022.pdf | 2022-11-15 |
| 34 | Priority Document [03-02-2016(online)].pdf | 2016-02-03 |
| 34 | 201617003890-IntimationOfGrant15-11-2022.pdf | 2022-11-15 |
| 1 | searchstrategyE_18-05-2020.pdf |