U.S. patent application number 16/084166 was filed with the patent office on 2020-09-17 for fucoidan hair growth agent.
The applicant listed for this patent is COSMED PHARMACEUTICAL CO., LTD.. Invention is credited to Fumio Kamiyama, Hidemasa Katsumi, Ying-shu Quan, Akira Yamamoto, Hirofumi Yamashita.
Application Number | 20200289548 16/084166 |
Document ID | / |
Family ID | 1000004873571 |
Filed Date | 2020-09-17 |
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United States Patent
Application |
20200289548 |
Kind Code |
A1 |
Quan; Ying-shu ; et
al. |
September 17, 2020 |
FUCOIDAN HAIR GROWTH AGENT
Abstract
To develop a novel administration method of a
fucoidan-containing hair-growing agent and to provide a means for
exerting excellent effects of a fucoidan. A hair-growing agent of
the present invention is characterized in that it is composed of a
combination of a fucoidan-containing microneedle and a
fucoidan-containing liniment. A base of the fucoidan-containing
microneedle is preferably a biosoluble polymer. A hair-growing
method of the present invention is characterized in that the
fucoidan-containing microneedle and the fucoidan-containing
liniment are concomitantly used.
Inventors: |
Quan; Ying-shu; (Kyoto-city,
Kyoto, JP) ; Yamashita; Hirofumi; (Kyoto-city, Kyoto,
JP) ; Kamiyama; Fumio; (Kyoto-city, Kyoto, JP)
; Yamamoto; Akira; (Kyoto-city, Kyoto, JP) ;
Katsumi; Hidemasa; (Kyoto-city, Kyoto, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
COSMED PHARMACEUTICAL CO., LTD. |
Kyoto-city, Kyoto |
|
JP |
|
|
Family ID: |
1000004873571 |
Appl. No.: |
16/084166 |
Filed: |
March 16, 2017 |
PCT Filed: |
March 16, 2017 |
PCT NO: |
PCT/JP2017/010571 |
371 Date: |
September 11, 2018 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/737 20130101;
A61K 36/23 20130101; A61M 2037/0061 20130101; A61M 2037/0023
20130101; A61M 37/0015 20130101; A61K 36/9068 20130101; A61P 17/14
20180101; A61K 9/06 20130101 |
International
Class: |
A61K 31/737 20060101
A61K031/737; A61K 9/06 20060101 A61K009/06; A61K 36/9068 20060101
A61K036/9068; A61K 36/23 20060101 A61K036/23; A61P 17/14 20060101
A61P017/14; A61M 37/00 20060101 A61M037/00 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 16, 2016 |
JP |
2016-074691 |
Claims
1. A hair-growing agent composed of a combination of a
fucoidan-containing microneedle and a fucoidan-containing
liniment.
2. The hair-growing agent according to claim 1, wherein a base of
the fucoidan-containing microneedle is a biosoluble polymer.
3. The hair-growing agent according to claim 1, wherein the
fucoidan in the fucoidan-containing microneedle and the
fucoidan-containing liniment is derived from a brown alga.
4. The hair-growing agent according to any one of claims 1 to 3,
further containing a carrot extract and a ginger tincture as a
drug.
5. A hair-growing method (excluding medical practice), wherein the
fucoidan-containing microneedle and the fucoidan-containing
liniment are concomitantly used.
6. A hair-growing agent composed of a fucoidan-containing
microneedle alone.
Description
TECHNICAL FIELD
[0001] The present invention relates to a hair-growing agent
composed mainly of fucoidan.
BACKGROUND ART
[0002] Fucoidan is a kind of acidic polysaccharide polymers
containing fucose sulfate as a main constituent sugar. Fucoidan is
a viscous component contained in brown algae such as Undaria
pinnatifida, Cladosiphon okamuranus and tangle weed, and is known
to have a hair-growing effect.
[0003] In relation to the hair-growing effect of fucoidan, a
hair-growing composition containing fucoidan (Patent Document 1), a
cosmetic containing fucoidan or a decomposed product thereof and
having a hair-growing effect (Patent Document 2), foods and drinks
containing fucoidan and having a hair-growing effect (Patent
Document 3), a fact that a high-molecular-weight fucoidan having an
average molecular weight of 1,000,000 or more is relatively
effective for hair growth (Patent Document 4), an oral hair-growing
agent with a combination of fucoidan and a seaweed-derived protein
(Patent Document 5), a hair-growing agent containing fucoidan and a
soybean protein (Patent Document 6), a hair-repairing agent
obtained by blending propolis and the like into fucoidan (Patent
Document 7) have already been published. All of them are oral
agents or liniments.
[0004] However, it is well known that even if a drug is orally
administered, the drug is not necessarily delivered to a site of a
body where an effect of the drug is expected to be exerted, and the
utilization rate of the oral drug is low in many cases. Also, it is
well known that even if the drug is applied to a particular site of
the body, a corneum acts as a barrier to drug penetration, and the
drug does not sufficiently penetrate merely by applying the drug to
the body surface. In particular, an efficiency of percutaneously
absorbing a high-molecular-weight drug is extremely low, and it is
difficult to exert effects only by absorption from the skin.
Fucoidan is an acidic polysaccharide polymer, its percutaneous
absorbability is extremely low, and only a minute amount thereof is
absorbed through pores.
[0005] Thus, the oral administration method and the application
method have a problem of inefficient drug use.
[0006] On the other hand, the application method can remarkably
improve the efficiency of penetrating the drug by perforating a
corneum using a minute needle i.e. a microneedle.
[0007] An item in which a lot of the microneedles are accumulated
on a substrate is called a microneedle array. In addition, a
product which is made easier to use by adding an adhesive tape for
attaching the microneedle array to a skin, a covering sheet for
keeping a sterile state until use, and the like to the microneedle
array, is called a microneedle patch. Herein, the tape refers to a
film, cloth or paper coated with an adhesive.
[0008] Although many attempts have already been made to
transdermally administer a drug using such a microneedle, its use
as a hair-growing agent seems not to have yet been reported.
[0009] The microneedle can be prepared using a water-insoluble
material such as stainless steel and polylactic acid, but a
microneedle made of a base (biosoluble polymer base) which
dissolves by water in a body such as carbohydrate as a substrate
can facilitate intradermal and subcutaneous administration of a
drug by previously blending the drug into the microneedle, because
the injected microneedle dissolves in the body. Herein, the
substrate refers to a main component constituting the
microneedle.
[0010] The microneedle array made of the biosoluble polymer
substance is often manufactured using a mold. A microneedle pattern
is formed by lithography using a photosensitive resin, followed by
transferring, to prepare a mold having recesses for forming
microneedles. A microneedle material is cast on this mold,
subsequently heated to evaporate moisture, and then the solidified
material is released from the mold to obtain a microneedle
array.
PRIOR ART DOCUMENTS
Patent Documents
Patent Document 1: Japanese Patent Application Laid-Open No.
2003-155218
Patent Document 2: Re-publication of WO 01/039731
Patent Document 3: Japanese Patent Application Laid-Open No.
2005-281277
Patent Document 4: Japanese Patent Application Laid-Open No.
2007-262036
Patent Document 5: Japanese Patent Application Laid-Open No.
2008-169140
Patent Document 6: Japanese Patent Application Laid-Open No.
2009-114170
Patent Document 7: Japanese Patent Application Laid-Open No.
2014-218440
SUMMARY OF INVENTION
Problem to be Solved
[0011] In a hair root area inside a scalp, there are hair bulbs
distributed in the dermic layer having a thickness of 0.5 to 1.5
mm, and hair grows by hair matrix cells inside the hair bulbs.
Although a hair-growing agent should be delivered to the dermic
layer, its skin penetration is prevented by a corneum barrier, and
this is why there are few commonly-effective percutaneous
hair-growing agents. The object of the present invention is to
develop a novel administration method of the fucoidan-containing
hair-growing agent and to provide a means for exerting excellent
effects of fucoidan.
Solution to Problem
[0012] The present inventors have continued examinations with hope
for the administration through the microneedles exerting a
hair-growing effect far superior to that of the conventional liquid
administration, and this examinations have led to the present
invention. The hair-growing agent according to the present
invention made in order to solve the above problems is
characteristically obtained by combining a fucoidan-containing
microneedle and a fucoidan-containing liniment.
[0013] In the present invention, it was found that although
administration of fucoidan is effective even by administering the
fucoidan-containing microneedle alone, the effect is further
enhanced by combining the fucoidan-containing microneedle with a
fucoidan-containing liquid (essence). Even only the
fucoidan-containing microneedle expresses a hair-growing effect far
superior to that in application of the fucoidan-containing essence
to skin. Furthermore, concomitant use (combination) of both
expresses a more excellent effect, which is a feature of the
present invention. Although the mechanism remains unclear, it is
considered that the mechanism is attributed to the percutaneous
penetration of fucoidan contained in the microneedles through skin
pores formed by the microneedles, and furthermore to the enhanced
intradermal penetration of fucoidan contained in the liquid.
[0014] That is, the hair-growing method of the present invention is
characterized in that the hair-growing effect is enhanced by
combining administration of the fucoidan-containing microneedles
and administration of the fucoidan-containing microneedles and
fucoidan-containing liquid. As for the timing of concomitant use,
the microneedles and the liquid may be simultaneously administered,
or each of them may be administered at another time.
[0015] The length of the fucoidan-containing microneedle is
suitably 0.1 to 1.5 mm. A more suitable length is 0.15 to 1.0 mm.
If the length is 0.1 mm or less, the function as a microneedle
cannot be sufficiently exhibited. If the length is 1.0 mm or more,
the effect is sufficient, but pain due to administration is
accompanied, causing problems on a user's compliance. As a base for
the microneedle containing fucoidan, a water-soluble polymer is
desirable. A biosoluble polymer such as hyaluronic acid, collagen,
hydroxypropyl cellulose and chondroitin sulfate is particularly
preferred, because skin moisture diffuses in the needle part within
a short period after its insertion and the needle part inserted
into the skin swells and then dissolves.
[0016] As a fucoidan-containing liniment, not only the liquid but
also a cream, a mousse, a gel, etc. can be used in combination with
a microneedle method. The amount of fucoidan blended in the
hair-growing agent varies depending on the dosage form,
administration method, desired effect, treatment period, etc. and
so cannot be unconditionally defined. However, it is appropriate
that its concentration in the liquid or the cream is typically 0.1
.mu.g/mL to 100 mg/mL. Additionally, in the microneedle
preparation, one dose is blended into one or several microneedle
arrays, and the dose is suitably 0.1 .mu.g to 2 mg per one
microneedle array.
[0017] In the hair-growing agent, other hair-growing promoters can
be added in order to complement or enhance its hair-growing
activity. For example, minoxidil, carpronium chloride, t-flavanone,
adenosine, 6-benzylaminopurine, pentadecanoic acid glyceride, crude
drug extract and the like are suitable.
[0018] In addition to the hair-growing promoter, if necessary, a
plant extract, an aqueous component, a moisturizer, a thickener, a
preservative, an antioxidant, a perfume, a coloring material, a
drug and the like which are approved as a drug, a cosmetic, a quasi
drug, a pharmaceutical and the like may be appropriately blended
into the hair-growing agent, as long as the purpose and the effect
of the hair-growing agent are not impaired.
[0019] The plant extract includes red pepper, aloe, tea leaf,
magnolia flower, Japanese horseradish, Ligustrum lucidum fruit,
spilanthes acmella, gardenia, asiasarum sieboldii, garlic, mint,
coix seed, Daemonorops draco, burdock, licorice, gynostemma
pentaphyllum, Ganoderma lucidum, rehmannia root, monoammonium
glycyrrhizinate, glycyrrhetinic acid, glycyrrhizin, sesame, cnidium
rhizome, polygonum root, rumex root, carrot, ginger tincture and
the like, and each of them can be used alone or in combination of
plural kinds.
Effects of Invention
[0020] The fucoidan-containing microneedle of the present invention
can exert a greater effect than in a case of using the conventional
liniment alone.
[0021] Furthermore, by combining the fucoidan-containing
microneedle administration and the fucoidan-containing liniment
administration, the hair-growing effect can be greater than in a
case of using either one of them alone.
[0022] The hair-growing agent of the present invention can be used
as any preparation which is widely usable for pharmaceuticals,
quasi-drugs, cosmetics and the like.
BRIEF DESCRIPTION OF DRAWINGS
[0023] FIG. 1 illustrates a figure showing a method for
manufacturing a fucoidan-containing microneedle array.
[0024] FIG. 2 illustrates a figure showing comparison of effects of
various administration methods for the hair-growing agent of this
patent application, and comparison of effects in combination with
other hair-growing agents. In the figure, the ordinate represents
an amount of the grown hair (mg/cm.sup.2).
[0025] FIG. 3A illustrates a photograph of a head showing a
hair-growing effect of a panelist in hair growth test 3.
[0026] FIG. 3B illustrates a photograph of a head showing a
hair-growing effect of another panelist in hair growth test 3.
[0027] FIG. 4 illustrates graphs showing a questionnaire result
regarding use of the hair-growing agent on the panelists after
completion of hair growth test 3.
[0028] FIG. 5 illustrates graphs showing evaluations regarding hair
restoration and hair loss on the panelists after completion of hair
growth test 3.
[0029] FIG. 6 illustrates a graph showing effects perceived by the
panelists after completion of hair growth test 3.
DESCRIPTION OF EMBODIMENTS
[0030] Hereinafter, embodiments of the present invention will be
explained on the basis of Examples. However, the present invention
is not limited to the contents of Examples.
[0031] As fucoidan of the present invention, a product purified
from Cladosiphon okamuranus was used. For this product, a
commercial product (LIMUVEIL, made by TANGLEWOOD K.K.) can be
used.
(Hair Growth Test 1)
[0032] A microneedle pattern having a predetermined shape was
formed as shown in FIG. 1 by a lithography method of irradiating a
photosensitive resin with light. This microneedle pattern was
electroformed to form a mold 10 having microneedle-forming recesses
11 onto which the pattern had been transferred. The
microneedle-forming recesses 11 have a stratovolcano shape with a
root diameter of 200 .mu.m and a depth of 300 .mu.m, arranged in a
lattice pattern at an interval of 600 .mu.m, and 280 recesses are
formed per 1 cm.sup.2. A microneedle array 12 was molded using the
recessed mold for formation of the present invention.
[0033] 5 g of hyaluronic acid (FCH-80, derived from culture, made
by Kikkoman Biochemifa Company) and 5 g of LIMUVEIL HV (aqueous
solution containing 1.2% of fucoidan, made by TANGLEWOOD K.K.) were
added to 90 g of water to prepare a homogeneous solution. The
aqueous solution was cast on the mold 10, dried at room temperature
for 24 hours, and released from the mold to obtain a microneedle
array sheet. This sheet was cut to obtain a microneedle array
having a diameter of 1 cm. A content of fucoidan per one
microneedle array was 25 .mu.g.
[0034] 0.1 g of LIMUVEIL HV was dissolved in 200 g of water to
prepare a fucoidan-containing extract.
[0035] The following animal experiment was carried out in an animal
test laboratory of Kyoto Pharmaceutical University in compliance
with the operative provision for animal experiment in Kyoto
Pharmaceutical University (rule of Kyoto Pharmaceutical University
in consideration of viewpoints of science, animal welfare and
environmental conservation, and health and safety of persons
engaged in animal experiment and the like, on the basis of basic
guideline on implementation of animal experiment and the like at
research institutes and the like (Public Notice of the Ministry of
Education, Sports, Culture, Science and Technology No. 71, in
2006)).
[0036] Male C3H/HeN mice (CHARLES RIVER LABORATORIES JAPAN, INC.)
were preliminarily raised, and at 6 weeks of age, their backs were
sheared by a hair-clipper, and furthermore shaved with a razor for
using the mice in the experiment.
[0037] A fucoidan-containing microneedle (fMN) and a
fucoidan-containing extract (fEX) were administered at a
predetermined time interval for 22 days, and after 24 days, an
amount of grown hair was measured.
[0038] In relation to the single dose, in the case of the
microneedle, one patch is applied, and in the case of the
inclusion-type extract, 50 .mu.L of the extract was applied on an
area of about 1 cm.sup.2. In both cases, the amounts of fucoidan
were the same, 25 .mu.g. The results are summarized in Table 1.
From Table 1, it can be found that the concomitant use of the
fucoidan-containing microneedle and the fucoidan-containing extract
is excellent in hair-growing effect.
[0039] In the hair growth test, the alternate-day administration
refers to an aspect that the fMN was administered on the first day
and the fEX was administered on the next day, and this cycle of the
fMN and fEX was continued 11 times for 22 days. The administration
of 2 days out of 3 days refers to an aspect that the fMN was
administered on the first day, the fEX was administered on the
second day and administration was suspended on the third day, and
this cycle was continued 8 times for 23 days. Note that, when the
hair-growing agent to be administered was one kind, the agent was
administered on the first and second days, and administration was
suspended on the third day, and this cycle was repeated 8 times (16
applications), which refers to administration continued for a total
of 23 days.
TABLE-US-00001 TABLE 1 Hair growth test result administered hair-
interval of amount of the test number growing agent administration
grown hair Example 1 fMN + fEX alternate-day 0.7 Example 2 fMN +
fEX 2 days out of 3 days 0.6 Comparative fMN 2 days out of 3 days
0.3 Example 1 Comparative fEX 2 days out of 3 days 0.1 Example 2
Comparative not administered 0 Example 3 Reference commercial
product alternate-day 0.2 Example 1
A unit of the amount of the grown hair is mg/cm.sup.2. The
commercial product in the Reference Example is a 5% minoxidil
aqueous solution (Taisho Pharmaceutical Co., Ltd.).
(Hair Growth Test 2)
[0040] The hair-growing effects were compared using
fucoidan-containing extract as a main active ingredient in various
administration methods. In the same manner as in the hair growth
test 1, C3H/HeN mice were sheared and shaved.
[0041] The administered drugs and administration methods are
summarized in Table 2. After 40 days, grown hair was shaved off,
washed, dried, and its weight was measured in order to quantitate
the hair growth state.
[0042] The administered drug was somewhat different from that in
the hair growth test 1. The microneedle array (MN) was not blended
with only 5 g of LIMUVEIL HV in the hair growth test 1, but 1 g of
carrot extract (MARUZEN PHARMACEUTICALS CO., LTD.) and 1 g of
ginger tincture (MARUZEN PHARMACEUTICALS CO., LTD.) were added to 5
g of LIMUVEIL HV. The method of manufacturing the microneedle array
is the same as in the hair growth test 1.
[0043] As a liniment, a LIMUVEIL liquid (LQ) was used. A fucoidan
content therein did not correspond to 0.1 g of LIMUVEIL HV in the
hair growth test 1, but corresponded to 0.02 g of carrot extract
(MARUZEN PHARMACEUTICALS CO., LTD.) and 0.02 g of ginger tincture
(MARUZEN PHARMACEUTICALS CO., LTD.) in addition to 0.1 g of
LIMUVEIL HV, and the production method for the liniment was exactly
the same as in the test 1.
[0044] For both MN and LQ, the doses were 25 .mu.g in terms of
fucoidan. For the reference example (commercial product), a 5%
minoxidil aqueous solution (RiUP) (X) was used, and its dose was 40
.mu.L.
[0045] The administration cycle of each preparation in the hair
growth test is shown in Table 2, and the result of the amount of
the grown hair 40 days after administration is shown in FIG. 2. A
unit of the amount of the grown hair is mg/cm.sup.2.
TABLE-US-00002 TABLE 2 Administration schedule day aspect 1 2 3 4 5
6 7 8 9 10 11 12 13 only LQ (1) LQ LQ LQ LQ LQ LQ only MN (1) MN MN
MN MN MN MN only LQ (2) LQ LQ LQ LQ LQ LQ LQ LQ LQ LQ LQ LQ only MN
(2) MN MN MN MN MN MN MN MN MN MN MN MN LQ + MN (1) MN MN LQ MN MN
LQ MN MN MN MN LQ LQ + MN (2) MN LQ MN LQ MN LQ MN LQ MN LQ MN LQ
LQ + MN (3) MN LQ LQ MN LQ LQ MN LQ LQ MN LQ LQ commercial product
X X X X X X
[0046] From the results in Table 2 and FIG. 2, it was found that it
was extremely effective to alternately administrate the microneedle
and the liquid as the administration method of fucoidan. In
relation to the administration program, it could be confirmed that
the fucoidan-containing extract was optimal as the main valuable
component, and concomitant administration of the microneedle
application and the liquid was more effective.
(Hair Growth Test 3)
[0047] Volunteers were tested at a specialized agency where
efficacies of cosmetics and quasi drugs were evaluated. Informed
consent was obtained from each volunteer subject, and various tests
were implemented. The outline of the implementation was as
follows.
1. Panelists: 4 males (48 to 57 years old), 8 females (47 to 59
years old) 2. Test period: 12 weeks
3. How to use
[0048] The hair-growing needle and the hair-growing liniment were
the same as those used in Example 2.
[0049] Number of applications of the hair-growing needle: 3
times/week
[0050] Number of applications of the hair-growing liniment:
morning/night use
4. Evaluation of effect
[0051] The effect was judged by head photographs between before and
12 weeks after the use. Two representative examples out of 12
subjects are shown. After 12 weeks, in the heads of the two
panelists, increase of hair around the area on which the
hair-growing needle had been pasted was remarkably observed with
the naked eye (FIGS. 3A and 3B).
[0052] Evaluation results and questionnaire results of 12 panelists
are shown (FIGS. 4 to 6). In relation to the use of the
hair-growing agent of the present invention, two-thirds of
panelists were satisfied, and 80% or more of panelists indicated
willingness to continue to use it (FIG. 4). In relation to the
decrease of hair loss and increase of hair, the majority of
panelists perceived its effect (FIG. 5), and it is considered that
the panelists who perceived the effect and the panelists who expect
future effects expressed their intention to continue the use.
Moreover, in addition to the decrease of hair loss and the hair
growth, effects such as increased hair thickness, volume-up of
hair, increased firmness and resilience of hair and decreased white
hair are also perceived, and it was found that 87% of the panelists
perceived any advantageous effect for hair (FIG. 6). 13% of
panelists answered that there was no effect, but no adverse effect
on hair was observed.
* * * * *