U.S. patent application number 10/398654 was filed with the patent office on 2004-01-15 for skin pore minimizers and skin elasticity improvers.
Invention is credited to Amano, Shinya, Fujimura, Tsutomu, Nishijima, Takafumi.
Application Number | 20040009140 10/398654 |
Document ID | / |
Family ID | 18791356 |
Filed Date | 2004-01-15 |
United States Patent
Application |
20040009140 |
Kind Code |
A1 |
Nishijima, Takafumi ; et
al. |
January 15, 2004 |
Skin pore minimizers and skin elasticity improvers
Abstract
This invention relates to skin pore tighteners each of which
comprises, as an active ingredient, a compound represented by the
following formula: R.sup.1-OG (1) wherein R.sup.1 represents an
alkyl or alkenyl group having 8 to 32 carbon atoms, and OG
represents a residual group obtained by removing a hydrogen atom
from a hydroxyl group of a polyhydric alcohol, monosaccharide or
oligosaccharide at least one hydroxyl group of which has been
sulfated or phosphatized, or a salt thereof, and also to skin
elasticity improvers each of which comprises, as an active
ingredient, a glyceryl ether derivative represented by the
following formula: 1 wherein R.sup.1 represents the same group as
defined above, and X.sup.1 and X.sup.2 each independently
represents a hydrogen atom, --SO.sub.3OH or --PO(OH).sub.2 with the
proviso that X.sup.1 and X.sup.2 are not hydrogen atoms at the same
time, or a salt thereof. The skin pore tighteners according to the
present invention have excellent effect in tightening skin pores
and rendering them less conspicuous, while the skin elasticity
improvers and skin tighteners according to the present invention
have superb effect in preventing and lessening skin wrinkles and
sagging. Accordingly, they are useful as ordinary cosmetic
preparations, as cosmetic preparations after depilating treatment,
and also as cosmetic preparations after removal of keratotic
plugs.
Inventors: |
Nishijima, Takafumi;
(Haga-gun Tochigi, JP) ; Amano, Shinya; (Tochigi,
JP) ; Fujimura, Tsutomu; (Tochigi, JP) |
Correspondence
Address: |
OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.
1940 DUKE STREET
ALEXANDRIA
VA
22314
US
|
Family ID: |
18791356 |
Appl. No.: |
10/398654 |
Filed: |
April 14, 2003 |
PCT Filed: |
June 29, 2001 |
PCT NO: |
PCT/JP01/05636 |
Current U.S.
Class: |
424/70.13 ;
536/107; 536/109 |
Current CPC
Class: |
A61K 8/55 20130101; A61K
8/604 20130101; C07C 279/14 20130101; A61Q 19/00 20130101; A61P
17/16 20180101; A61K 8/463 20130101; C07F 9/091 20130101; A61K
8/602 20130101; A61Q 19/08 20130101 |
Class at
Publication: |
424/70.13 ;
536/107; 536/109 |
International
Class: |
A61K 007/06; A61K
007/11; C08B 031/02; C08B 033/02; C08B 035/02 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 12, 2000 |
JP |
2000311627 |
Claims
1. A skin pore tightener comprising a keratinocyte contracting
agent as an active ingredient.
2. A keratinocyte contracting agent comprising, as an active
ingredient, a compound represented by the following formula (1):
R.sup.1-OG (1)wherein R.sup.1 represents an alkyl or alkenyl group
having 8 to 32 carbon atoms, and OG represents a residual group
obtained by removing a hydrogen atom from a hydroxyl group of a
polyhydric alcohol, monosaccharide or oligosaccharide at least one
hydroxyl group of which has been sulfated or phosphatized, or a
salt thereof:
3. A skin pore tightener comprising, as an active ingredient, a
compound represented by the following formula (1): R.sup.1-OG
(1)wherein R.sup.1 represents an alkyl or alkenyl group having 8 to
32 carbon atoms, and OG represents a residual group obtained by
removing a hydrogen atom from a hydroxyl group of a polyhydric
alcohol, monosaccharide or oligosaccharide at least one hydroxyl
group of which has been sulfated or phosphatized, or a salt
thereof.
4. A skin elasticity improver comprising, as an active ingredient,
a glyceryl ether derivative represented by the following formula
(2): 5wherein R.sup.1 represents an alkyl or alkenyl group having 8
to 32 carbon atoms, and X.sup.1 and X.sup.2 each independently
represents a hydrogen atom, --SO.sub.3OH or --PO(OH).sub.2 with the
proviso that X.sup.1 and X.sup.2 are not hydrogen atoms at the same
time, or a salt thereof.
5. A skin elasticity improver according to claim 4, which prevents
and/or lessens skin wrinkles and sagging.
6. A skin tightener comprising as an active ingredient a glyceryl
ether derivative or a salt thereof as defined in claim 4.
7. A skin pore tightening method, which comprises applying a
keratinocyte contracting agent.
8. A skin pore tightening method, which comprises applying to the
skin a compound or a salt thereof as defined in claim 2.
9. A method for preventing and/or lessening skin wrinkles and
sagging, which comprises applying to the skin a glyceryl ether
derivative or a salt thereof as defined in claim 4.
10. A phosphatized glyceryl ether derivative represented by the
following formula (3): 6wherein R.sup.2 represents isostearyl,
2-hexyldecyl, 2-heptylundecyl, 2-octyldodecyl, 2-decyltetradecyl,
2-dodecylhexadecyl, 2-tetradecyloctadecyl, 2-hexadecyleicosyl or
2-(1,3,3-trimethylbutyl)-5,7- ,7-trimethyloctyl, or a salt thereof.
Description
TECHNICAL FIELD
[0001] This invention relates to skin pore tighteners capable of
acting on epidermal cells of the skin and rendering skin pores less
conspicuous, and also to skin elasticity improvers capable of
preventing and lessening skin wrinkles and sagging.
BACKGROUND ART
[0002] Women's skin troubles include wrinkles, sagging, suppleness
reductions, pigmentation and conspicuous skin pores, among which
wrinkles, sagging and conspicuous skin pores are ranked high. As
causes of conspicuous skin pores, there are keratotic plugs formed
in skin pores, pigmentation, and the shape of skin pore openings.
For keratotic plugs out of these causes, various keratotic plug
removers have been developed, and have found wide-spread utility.
Use of these keratotic plug removers are, however, accompanied by a
drawback in that, even after keratotic plugs have been removed,
skin pores are conversely rendered more conspicuous unless they
become smaller.
[0003] Skin wrinkles and sagging, on the other hand, occur as a
result of a loss of skin elasticity upon aging. For their
lessening, nothing is practiced except for mere use of
collagen-added cosmetic preparations or mere application of
astringents or the like, which show temporary serofluid decreasing
and vasoconstrictive effects, to local sites. No agent has been
found yet to improve skin elasticity.
[0004] Therefore, there has been a demand for development of a skin
pore tightener capable of tightening skin pores themselves and
rendering them less conspicuous and also a skin elasticity improver
capable of improving skin elasticity and preventing and lessening
skin wrinkles and sagging.
DISCLOSURE OF THE INVENTION
[0005] The present inventors have proceeded with an investigation
on a possible correlation between the contraction of epidermal
cells and the skin. Quite unexpectedly, it has been found that
application of an ingredient, which causes strong contraction of
keratinocytes, can tighten skin pores and render them less
conspicuous. It has also been found that the sulfates or phosphates
of alkyl-containing polyhydric alcohols or saccharides induce
strong contraction of keratinocytes and are also excellent in skin
pore tightening effect and further, that the sulfates or phosphates
of alkyl-containing glycerins have superb skin elasticity improving
effect and skin tightening effect and are also effective in
preventing and lessening skin wrinkles and sagging.
[0006] Specifically, the present invention provides a skin pore
tightener which comprises a keratinocyte contracting agent as an
active ingredient.
[0007] The present invention also provides a keratinocyte
contracting agent and skin pore tightener, each of which comprises,
as an active ingredient, a compound represented by the following
formula (1):
R.sup.1-OG (1)
[0008] wherein R.sup.1 represents an alkyl or alkenyl group having
8 to 32 carbon atoms, and OG represents a residual group obtained
by removing a hydrogen atom from a hydroxyl group of a polyhydric
alcohol, monosaccharide or oligosaccharide at least one hydroxyl
group of which has been sulfated or phosphatized, or a salt
thereof.
[0009] The present invention also provides a skin elasticity
improver and skin tightener, each of which comprises, as an active
ingredient, a glyceryl ether derivative represented by the
following formula (2): 2
[0010] wherein R.sup.1 represents the same group as defined above,
and X.sup.1 and X.sup.2 each independently represents a hydrogen
atom, --SO.sub.3OH or --PO(OH).sub.2 with the proviso that X.sup.1
and X.sup.2 are not hydrogen atoms at the same time, or a salt
thereof.
[0011] The present invention also provides a skin pore tightening
method, which comprises applying to the skin a keratinocyte
contracting agent or a compound represented by the formula (1) or a
salt thereof.
[0012] The present invention further provides a method for
preventing and/or lessening skin wrinkles and sagging, which
comprises applying to the skin a glyceryl ether derivative
represented by the formula (2) or a salt thereof.
[0013] The present invention still further provides a phosphatized
glyceryl ether derivative represented by the following formula (3):
3
[0014] wherein R.sup.2 represents isostearyl, 2-hexyldecyl,
2-heptylundecyl, 2-octyldodecyl, 2-decyltetradecyl,
2-dodecylhexadecyl, 2-tetradecyloctadecyl, 2-hexadecyleicosyl or
2-(1,3,3-trimethylbutyl)-5,7- ,7-trimethyloctyl, or a salt
thereof.
BEST MODES FOR CARRYING OUT THE INVENTION
[0015] No particular limitation is imposed on the keratinocyte
contracting agent for use in the skin pore tightener according to
the present invention insofar as it is an ingredient capable of
causing contraction of keratinocytes, and examples thereof include,
an ingredient which exhibits contracting action on a collagen gel
to which human epidermal keratinocytes is attached. Specific
examples can include compounds represented by the formula (1) and
salts thereof.
[0016] In the formula (1), the alkyl group represented by R.sup.1
is preferably an alkyl group having 8 to 32 carbon atoms,
particularly 10 to 22 carbon atoms, more preferably 16 to 20 carbon
atoms. Further, the alkyl group may be either linear or branched
although the branched one is preferred from the standpoint of
effects. Specific examples can include n-decyl, trimethyldecyl,
n-undecyl, 2-heptylundecyl, n-dodecyl, n-tridecyl, n-tetradecyl,
n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl,
methylheptadecyl (isostearyl), 2-heptylundecyl, n-nonadecyl,
n-icosyl, and n-docosyl. Among these, particularly preferred are
branched alkyl groups having 10 to 22 carbon atoms such as
isotridecyl, isopalmityl, methylheptadecyl (isostearyl), and
2-heptylundecyl.
[0017] Incidentally, an isostearyl group is a mixture of isostearyl
groups containing methyl branches at various positions primarily on
their respective backbones, because isostearyl alcohol obtained by
reducing isostearic acid, which is formed as a byproduct upon
production of a dimer acid from beef tallow, soybean oil or the
like, is used as a raw material.
[0018] The alkenyl group represented by R.sup.1 can preferably be a
linear or branched alkenyl group having 8 to 32 carbon atoms, with
one having 10 to 22 carbon atoms being more preferred. Specific
examples can include 10-undecenyl, 9-octadecenyl (oleyl),
9,12-octadienyl, and 13-docosenyl.
[0019] In the formula (1), OG represents a residual group obtained
by removing a hydrogen atom from a hydroxyl group of a polyhydric
alcohol, monosaccharide or oligosaccharide at least one hydroxyl
group of which has been sulfated or phosphatized; specifically,
residual groups of sulfated or phosphatized polyhydric alcohols,
such as sulfated or phosphatized propanediol group, sulfated or
phosphatized glyceryl group, and sulfated or phosphatized mannitol
group; residual groups of sulfated or phosphatized monosaccharides;
and residual groups of sulfated or phosphatized
oligosaccharides,.
[0020] Examples of the polyhydric alcohol can include ethylene
glycol, propylene glycol, 1,3-propanediol, glycerin, mannitol,
pentaerythritol, and sorbitol, with glycerin being particularly
preferred.
[0021] Examples of the monosaccharide can include aldopentoses and
aldohexoses, such as xylose, arabinose, ribose, glucose, galactose,
mannose, talose, idose, altrose, allose and gulose. The
oligosaccharide is preferably one having 5 or less constituent
monosaccharides from the standpoint of effects, with one having 2
to 3 constituent monosaccharides being particularly preferred.
Further, the glycoside bond between each two monosaccharides is
preferably (1.fwdarw.2), (1.fwdarw.4) or (1.fwdarw.6), although no
limitation is imposed in this respect. In addition, the linkage can
be either the .alpha.-linkage or the .beta.-linkage.
[0022] Examples of the oligosaccharide can include
homooligosaccharides such as glucooligosaccharide,
galactooligosaccharide, mannooligosaccharide and
fructooligosaccharide, oligosaccharides composed of pentoses and
hexoses, and oligosaccharides composed of different hexoses.
Particularly preferred are oligosaccharides each of which is
composed of a repetition of glucose molecules.
[0023] There is .alpha./.beta. stereoisomerism in each of the
linkages between these monosaccharide or oligosaccharide residual
groups and R.sup.1. Such stereoisomers are both included in the
present invention, but the .beta.-linkage is preferred when the
saccharide residual group is galactose residual group.
[0024] When OG is a residual group of a sulfated or phosphatized
polyhydric alcohol, for example, a sulfated or phosphatized
glyceryl group, the compound of the formula (1) is a mono- or
disulfate ester or a mono- or diphosphate ester. They can be used
either singly or in combination. When OG is a residual group of a
sulfated or phosphatized monosaccharide or oligosaccharide, on the
other hand, the compound of the formula (1) means such a compound
that the hydroxyl groups of the monosaccharide or oligosaccharide
moiety except for the 1-hydroxyl group have been sulfated or
phosphatized either in part or in whole, to form sulfates or
phosphates. From the standpoint of effects, however, one sulfated
or phosphatized to an extent of 10 to 30% or so based on the whole
hydroxyl groups is preferred.
[0025] Examples of the salts of the compounds of the formulas (1),
(2) and (3) can include salts with alkali metals such as lithium,
sodium and potassium, salts with alkaline earth metals such as
beryllium, magnesium and calcium, salts with primary, secondary or
tertiary amines, quaternary ammonium salts, and salts with amino
acids such as arginine and lysine. Of these, from the standpoint of
effects, the sodium salts, potassium salts, quaternary ammonium
salts and arginine salts are preferred, with the sodium salts and
arginine salts being preferred.
[0026] Among such OGs, a sulfated or phosphatized glyceryl group is
particularly preferred. In this case, the compound of the formula
(1) is a glyceryl ether derivative represented by the following
formula (2): 4
[0027] wherein R.sup.1 represents the same group as defined above,
and X.sup.1 and X.sup.2 each independently represents a hydrogen
atom, --SO.sub.3OH or --PO(OH).sub.2 with the proviso that X.sup.1
and X.sup.2 are not hydrogen atoms at the same time.
[0028] As will be demonstrated in Examples to be described
subsequently herein, such glyceryl ether derivatives have skin
elasticity improving effect and skin tightening effect in addition
to excellent skin pore constricting effect so that they are also
usable as skin elasticity improvers and skin tighteners.
[0029] Incidentally, phosphatized glyceryl ether derivative have
been known to have emulsion stabilizing effect or hypotensive
effect (JP-A-58104624, JP-A-60060195, Arzneim.-Forsch./Drug Res.,
35(I), Nr. 3, 587-592 (1985)), but are not known at all to have
skin pore constricting effect and skin elasticity improving
effect.
[0030] Among the above-described glyceryl ether derivatives,
phosphatized glyceryl ether derivatives in which one of X.sup.1 and
X.sup.2 is --PO(OH).sub.2 and R.sup.1 is isostearyl, 2-hexyldecyl,
2-heptylundecyl, 2-octyldodecyl, 2-decyltetradecyl,
2-dodecylhexadecyl, 2-tetradecyloctadecyl, 2-hexadecyleicosyl or
2-(1,3,3-trimethylbutyl)-5,7- ,7-trimethyloctyl are novel compounds
which have not been disclosed yet in any publications.
[0031] Among such glyceryl ether derivatives represented by the
formula (2), preferred examples can include sulfated glyceryl ether
derivatives such as 1-dodecylglycerol-3-sulfate,
1-octadecylglycerol-3-sulfate, 1-isostearylglycerol-3-sulfate and
1-dodecylglycerol-2,3-disulfate, and salts thereof; and
phosphatized glyceryl ether derivatives such as
1-decylglycerol-3-phosphate, 1-dodecylglycerol-3-phosphate,
1-tetradecylglycerol-3-phosphate, 1-hexadecylglycerol-3-phosphate,
1-octadecylglycerol-3-phosphate,
1-(2-heptylundecyl)glycerol-3-phosphate,
1-isostearylglycerol-3-phosphate, 1-oleylglycerol-3-phosphate and
1-dodecylglycerol-2,3-diphosphate, and salts thereof. In
particular, the arginine salts of
1-(2-heptylundecyl)glycerol-3-phosphate and
1-isostearylglycerol-3-phosphate have high utility because, as will
be demonstrated in the Examples to be described subsequently
herein, they exhibit outstanding skin pore constricting effect
along with excellent skin elasticity improving effect, and are also
superb in productivity.
[0032] Illustrative, preferred glycoside compounds can include
1-.alpha.-O-dodecylglucopyranoside-6-sulfate,
1-.beta.-O-dodecylglucopyra- noside-6-sulfate,
1-.alpha.-O-(2-heptylundecyl)glucopyranoside-6-sulfate,
1-.beta.-O-(2-heptylundecyl)glucopyranoside-6-sulfate,
octadecylglycopyranosidesulfate,
1-.alpha.-O-tetradecylgalactopyranoside-- 6-sulfate,
1-.beta.-O-tetradecylgalactopyranoside-6-sulfate, and the like.
[0033] Illustrative, preferred diol compounds can include
1-dodecylpropanediol-3-sulfate, 1-dodecylpropanediol-3-phosphate,
and the like.
[0034] Further, preferred examples of the polyhydric alcohol can
include 1-isostearylmannitol-5-sulfate,
1-isostearylmannitol-5-phosphate, and the like.
[0035] The glyceryl compounds in the present invention can each be
obtained, for example, by sulfating or phosphatizing a diol ether
or glyceryl ether and optionally neutralizing the resultant sulfate
or phosphate with an alkali as needed.
[0036] For the sulfating reaction, a known sulfating agent, for
example, fuming sulfuric acid, concentrated sulfuric acid, sulfamic
acid, chlorosulfonic acid, sulfur trioxide, the dioxane or pyridine
complex of sulfur trioxide, or the like can be used [Jikken Kagaku
Koza (Experimental Chemistry Series) 19, Organic Compound Synthesis
I, 201-203]. For the phosphatizing reaction, on the other hand,
phosphorus oxychloride, phosphorus trichloride, phosphorus
pentachloride, polyphosphoric acid, water-phosphoric acid
anhydride, phosphoric acid-phosphoric acid anhydride, or the like
can be used [Jikken Kagaku Koza (Experimental Chemistry Series),
Organic Compound Synthesis I, 206-210].
[0037] The glycoside compounds in the present invention can each be
produced based on a known synthesis process [Carbohydro. Res., 230,
245 (1992)]. Among such known synthesis processes, the process in
which a sugar peracetate is reacted with an alcohol under acidic
condition is preferred for its simplicity. Described specifically,
a reducing sugar in which all the hydroxyl groups have been
acetylated beforehand, and an alcohol are subjected to
glycosidation in the presence of an acid catalyst, and then,
hydrolysis is conducted for deacetylation, followed by sulfation or
phosphatization.
[0038] As will be demonstrated in the Examples to be described
subsequently herein, the compounds of the formula (1) thus obtained
and their salts have excellent keratinocyte contracting effect, and
are useful as keratinocyte contracting agents.
[0039] Furthermore, application of the keratinocyte contracting
agents to the skin can obtain excellent skin pore tightening
effect. Accordingly, the keratinocyte contracting agents are useful
as skin pore tighteners.
[0040] Among the compounds represented by the formula (1) and their
salts, the glyceryl ether derivatives represented by the formula
(2) and their salts have excellent skin elasticity improving
effect, and are useful as skin elasticity improvers and skin
tighteners for the prevention and lessening of skin wrinkles and
sagging.
[0041] The keratinocyte contracting agents and skin pore tighteners
as well as the skin elasticity improvers and skin tighteners is
preferably applied to the skin as cosmetic preparations for
rendering skin pores, wrinkles and sagging less conspicuous. It is
particularly preferred to use them in the form of medicated
external skin preparations, such as ointments, or cosmetic external
skin preparations, specifically in various forms such as emulsified
cosmetic preparations, creams, emulsions, lotions, and gels. Upon
formulation of such preparations, it is possible to add, in
addition to a compound of the formula (1) or (2) or a salt thereof,
those employed commonly in such preparation forms, i.e., oily bases
such as vegetable oils and animal oils, antiphlogistics,
analgesics, antiseptics, astrigents, emollients, hormone
preparations, vitamins, humectants, ultraviolet absorbers,
alcohols, chelating agents, pH adjusters, preservatives, viscosity
increasing agents, colorants, fragrance ingredients, etc. to
extents not impairing the advantageous effects of the present
invention.
[0042] The compound of the formula (1) or (2) or its salt can be
added in a proportion of from 0.001 to 20 wt. %, especially from
0.01 to 5 wt. % to the above-described external preparations for
the skin.
EXAMPLES
Production Example 1
[0043] Production of 1-Isostearylglycerol-3-Sulfate Sodium Salt
(Compound 3)
[0044] Isostearyl glyceryl ether (10 g, 0.029 mol) was dissolved in
anhydrous pyridine, and subsequent to cooling with ice, sulfur
trioxide-pyridine complex (4.6 g, 0.029 mol) was added. The
resulting mixture was stirred for 1 hour under ice cooling, and
then stirred at room temperature for 12 hours. After pyridine was
distilled off, purified water and sodium hydroxide (1.16 g, 0.029
mol) were added, followed by lyophilization to afford
1-isostearylglycerol-3-sulfate sodium salt (13.8 g).
[0045] In a similar manner as in Production Example 1, were
obtained 1-dodecylglycerol-3-sulfate sodium salt (Compound 1),
1-octadecylglycerol-3-sulfate sodium salt (Compound 2),
1-.alpha.-O-dodecylglucopyranoside-6-sulfate sodium salt (Compound
13), 1-.beta.-O-dodecylglucopyranoside-6-sulfate sodium salt
(Compound 14),
1-.alpha.-o-(2-heptylundecyl)glucopyranoside-6-sulfate sodium salt
(Compound 15),
1-.beta.-o-(2-heptylundecyl)glucopyranoside-6-sulfate sodium salt
(Compound 16), dodecylglucopyranosidesulfate sodium salt mixture
(Compound 17), octylglucopyranosidesulfate sodium salt mixture
(Compound 18), tetradecylglucopyranosidesulfate sodium salt mixture
(Compound 19), octadecylglucopyranosidesulfate sodium salt mixture
(Compound 20), (2-heptylundecyl)glucopyranosidesulfate sodium salt
mixture (Compound 21), methylheptadecylglucopyranosidesulfate
sodium salt mixture (Compound 22),
1-.alpha.-O-tetradecylgalactopyranoside-6-sulfate sodium salt
(Compound 23), 1-.beta.-o-tetradecylgalactopyranoside-6-sulfa- te
sodium salt (Compound 24), and 1-isostearylmannitol-5-sulfate
sodium salt (Compound 30).
Production Example 2
[0046] Production of 1-Isostearylglycerol-3-Phosphate Disodium Salt
(Compound 9)
[0047] Isostearyl glyceryl ether (5 g, 0.015 mol) was dissolved in
hexane, and 105% polyphosphoric acid (6.8 g, 0.075 mol) was added
at 50.degree. C., followed by stirring at 70.degree. C. for 12
hours. Subsequently, distilled water (10 g) was added, and the
resulting mixture was stirred for 3 hours. After the mixture was
allowed to cool down, ethanol was added, and the water layer was
separated off. After the organic layer was concentrated, purified
water and sodium hydroxide were added, followed by lyophilization
to afford 1-isostearylglycerol-3-phosphate disodium salt (7.1
g).
Production Example 3
[0048] Production of 1-(2-Heptylundecyl)glycerol-3-Phosphate
Disodium Salt (Compound 28)
[0049] Using 2-heptylundecyl glyceryl ether, production was
conducted in a similar manner as in Production Example 2 to afford
1-(2-heptylundecyl)glycerol-3-phosphate disodium salt.
[0050] In a similar manner as in Production Examples 2 and 3, were
obtained 1-decylglycerol-3-phosphate disodium salt (Compound 4),
1-dodecylglycerol-3-phosphate disodium salt (Compound 5),
1-tetradecylglycerol-3-phosphate disodium salt (Compound 6),
1-hexadecylglycerol-3-phosphate disodium salt (Compound 7),
1-octadecylglycerol-3-phosphate disodium salt (Compound 8),
1-oleylglycerol-3-phosphate disodium salt (Compound 10), and
1-isostearylmannitol-5-phosphate disodium salt (Compound 29).
Production Example 4
[0051] Production of 1-Dodecylglycerol-2,3-Disulfate Sodium Salt
(Compound 11)
[0052] Dodecyl glyceryl ether (10 g, 0.039 mol) was dissolved in
anhydrous pyridine, and at room temperature, sulfur
trioxide-pyridine complex (31 g, 0.195 mol) was added. The
resulting mixture was stirred at 70.degree. C. for 1 hour. After
pyridine was distilled off, purified water and sodium hydroxide
were added, followed by lyophilization to afford
1-dodecylglycerol-2,3-disulfate sodium salt (11.5 g).
Production Example 5
[0053] Production of 1-Dodecylglycerol-2,3-Diphosphate Disodium
Salt (Compound 12)
[0054] Dodecyl glyceryl ether (2 g, 7.7 mmol) was dissolved in
anhydrous pyridine, and at -20.degree. C., diphenylphosphoric acid
chloride (10.4 g, 0.0387 mol) was added dropwise over 1 hour.
Subsequent to stirring at the same temperature for 48 hours,
deionized water (0.75 g) was added, and pyridine was distilled off
under reduced pressure. The residue was extracted with ethyl ether.
The extract was washed successively with dilute hydrochloric acid
and water, and ethyl ether was distilled off. The residue was then
subjected to column chromatography to afford a reaction
intermediate (2.63 g).
[0055] The reaction intermediate (0.5 g, 0.69 mmol) was then
dissolved in acetic acid, and subsequent to addition of platinum
oxide (0.2 g), stirring was conducted at room temperature for 3
hours while bubbling hydrogen. Platinum oxide was filtered off, and
acetic acid was distilled off. Purified water and sodium hydroxide
were then added. Subsequent to lyophilization, the lyophilizate was
washed with methanol to afford 1-dodecylglycerol-2,3-diphosphate
disodium salt (0.33 g).
Production Example 6
[0056] Production of 1-Dodecylpropanediol-3-Sulfate Sodium Salt
(Compound 25)
[0057] 1-dodecylpropanediol (0.5 g, 1.8 mmol) was dissolved in
anhydrous pyridine, and subsequent to ice cooling, sulfur
trioxide-pyridine complex (0.58 g, 3.6 mmol) was added. The
resulting mixture was stirred under ice cooling for 1 hour. The
mixture was then stirred at room temperature for 12 hours. After
pyridine was distilled off, purified water and sodium hydroxide
(0.072 g, 1.8 mmol) were added, followed by lyophilization to
afford 1-dodecylpropanediol-3-sulfate sodium salt (0.6 g).
Production Example 7
[0058] Production of 1-Dodecylpropanediol-3-Phosphate Disodium Salt
(Compound 26)
[0059] 1-Dodecylpropanediol (0.5 g, 1.8 mmol) was dissolved in
hexane, and 105% polyphosphoric acid (0.85 g, 9 mmol) was added at
50.degree. C., followed by stirring at 70.degree. C. for 12 hours.
Subsequently, distilled water (10 g) was added, and the resulting
mixture was stirred for 3 hours. After the mixture was allowed to
cool down, ethanol was added, and the water layer was separated
off. After the organic layer was concentrated, purified water and
sodium hydroxide were added, followed by lyophilization to afford
1-dodecylpropanediol-3-phosphate disodium salt (0.66 g).
Production Example 8
[0060] Production of Dodecylglucopyranosidephosphate Disodium Salt
Mixture (Compound 27)
[0061] A dodecylglucopyranoside mixture (1.0 g, 2.9 mmol) was
dissolved in chloroform, and anhydrous pyridine (0.54 g, 6.8 mmol)
was added. After the resulting mixture was cooled to -20.degree.
C., phosphorus oxychloride (0.88 g, 5.7 mmol) was added, followed
by stirring for 4 hours. Subsequently, the mixture was poured into
a great deal of iced water, ethanol was added, and the
thus-obtained mixture was then homogenized. The mixture was
neutralized to pH 8.5 with sodium hydroxide, and the solvent was
distilled off. After the resultant residue was dissolved in
ethanol, insoluble matter was removed, and the solvent was
distilled off again to afford dodecylglucopyranosidephosphate
disodium salt mixture (1.20 g, 2.54 mmol).
Production Example 9
[0062] Production of 1-Isostearylglycerol-3-Phosphate Monoarginine
Salts (Compounds 31-A, 31-B)
[0063] 95% Phosphoric acid (47.4 g, 0.459 mol) was mixed in toluene
(150 mL), and isostearyl glycidyl ether (50 g, 0.153 mol), which
had been produced using beef-tallow-derived isostearyl alcohol as a
raw material, was added dropwise at room temperature over 30
minutes under nitrogen. The resulting mixture was then stirred
further for 2 hours, distilled water (50 g) and isopropyl alcohol
(25 g) were added, and the water layer was separated off. The
organic layer was washed with a 2.5% aqueous solution of sodium
sulfate, and the organic layer was concentrated to obtain crude
1-isostearylglycerol-3-phosphate. The crude
1-isostearylglycerol-3-phosphate so obtained was dissolved in an
ethanol-hexane mixed solvent. At 50.degree. C., L-arginine (26.65
g, 0.153 mol) was added gradually, followed by stirring at
70.degree. C. for 2 hours. Insoluble matter was removed by
filtration, the filtrate was gradually added into acetone which had
been cooled to 10.degree. C. or lower, and precipitated white
powder was washed with acetone and then dried to afford
1-isostearylglycerol-3-phosphate monoarginine salt (66.0 g, 72%
yield). Using isostearyl glycidyl ether that had been produced
using soybean-derived isostearyl alcohol as a raw material,
1-isostearylglycerol-3-phosphate monoarginine salt (Compound 31-B)
was obtained likewise.
Production Example 10
[0064] Production of 1-(2-Heptylundecyl)-Glycerol-3-Phosphate
Monoarginine Salt (Compound 32)
[0065] Using 2-heptylundecyl glycidyl ether, production was
conducted in a similar manner as in Production Example 9 to afford
1-(2-heptylundecyl)glycerol-3-phosphate monoarginine salt.
Production Example 11
[0066] Production of 1-(2-Hexyldecyl)-Glycerol-3-Phosphate
Monoarginine Salt (Compound 33)
[0067] Using 2-hexyldecyl glycidyl ether, production was conducted
in a similar manner as in Production Example 9 to afford
1-(2-hexyldecyl)glycerol-3-phosphate monoarginine salt.
Production Example 12
[0068] Production of 1-(2-Octyldodecyl)-Glycerol-3-Phosphate
Monoarginine Salt (Compound 34)
[0069] Using 2-octyldodecyl glycidyl ether, production was
conducted in a similar manner as in Production Example 9 to afford
1-(2-octyldodecyl)glycerol-3-phosphate monoarginine salt.
Production Example 13
[0070] Production of
1-[2-(1,3,3-Trimethylbutyl)-5,7,7-Trimethyloctyl]-Gly-
cerol-3-Phosphate Monoarginine Salt (Compound 35)
[0071] Using 2-(1,3,3-trimethylbutyl)-5,7,7-trimethyloctyl glycidyl
ether, production was conducted in a similar manner as in
Production Example 9 to afford
1-[2-(1,3,3-trimethylbutyl)-5,5,7-trimethyloctyl]-glycerol-3-ph-
osphate monoarginine salt.
Production Example 14
[0072] Production of 1-Dodecylglycerol-3-Phosphate Monoarginine
Salt (Compound 36)
[0073] Using dodecyl glycidyl ether, production was conducted in a
similar manner as in Production Example 9 to afford
1-dodecylglycerol-3-phosphate monoarginine salt.
Production Example 15
[0074] Production of 1-Tetradecylglycerol-3-Phosphate Monoarginine
Salt (Compound 37)
[0075] Using tetradecyl glycidyl ether, production was conducted in
a similar manner as in Production Example 9 to afford
1-tetradecylglycerol-3-phosphate monoarginine salt.
Production Example 16
[0076] Production of 1-Hexadecylglycerol-3-Phosphate Monoarginine
Salt (Compound 38)
[0077] Using hexadecyl glycidyl ether, production was conducted in
a similar manner as in Production Example 9 to afford
1-hexadecylglycerol-3-phosphate monoarginine salt.
Production Example 17
[0078] Production of 1-Octadecylglycerol-3-Phosphate Monoarginine
Salt (Compound 39)
[0079] Using octadecyl glycidyl ether, production was conducted in
a similar manner as in
Production Example 9 to afford 1-octadecylglycerol-3-phosphate
monoarginine salt.
Production Example 18
[0080] Production of 1-Oleylglycerol-3-Phosphate Monoarginine Salt
(Compound 40)
[0081] Using oleyl glycidyl ether, production was conducted in a
similar manner as in
Production Example 9 to afford 1-oleylglycerol-3-phosphate
monoarginine salt.
Production Example 19
[0082] Production of 1-(2-Decyltetradecyl)-3-Phosphate Monoarginine
Salt (Compound 41)
[0083] Using 2-decyltetradecyl glycidyl ether, production was
conducted in a similar manner as in Production Example 9 to afford
1-(2-decyltetradecyl)glycerol-3-phosphate monoarginine salt.
Production Example 20
[0084] Production of 1-(2-Dodecylhexadecyl)-Glycerol-3-Phosphate
Monoarginine Salt (Compound 42)
[0085] Using 2-dodecylhexadecyl glycidyl ether, production was
conducted in a similar manner as in Production Example 9 to afford
1-(2-dodecylhexadecyl)glycerol-3-phosphate monoarginine salt.
[0086] Spectral data on novel compounds out of Compounds 1 to 42
are presented in Table 1.
1 TABLE 1 .sup.1H-NMR spectrum Solvent for IR spectrum (cm.sup.-1,
sample Compound KBr tablet method) .delta., ppm preparation
Compound 3 3376, 2932, 2860, 1470, 4.12-4.01, D.sub.2O--CD.sub.3OD
1270, 1230, 1124 3.60-3.40, 1.60, 1.30, 0.89 Compound 9 3440, 2932,
2860, 1468, 4.24, 4.01- D.sub.2O--CD.sub.3OD 1120, 982 3.43, 1.62,
1.31, 0.89 Compound 11 2932, 2860, 1472, 1270, 4.64, 4.23,
D.sub.2O--CD.sub.3OD 1240, 1118 3.74, 3.56, 1.58, 1.28, 0.87
Compound 12 2932, 2860, 1470, 1106, 4.23, 3.83,
D.sub.2O--CD.sub.3OD 982 3.69, 3.57, 1.57, 1.26, 0.85 Compound 23
2924, 2856, 1470, 1252, 3.93, 3.57- D.sub.2O--CD.sub.3OD (mixture)
1208, 1130 3.28, 1.82, 1.65, 1.14, 0.72 Compound 24 2856, 1472,
1254, 1116 3.60-3.30, D.sub.2O--CD.sub.3OD (mixture) 1.89, 1.58,
1.28, 0.87 Compound 27 3440, 2932, 2860, 1470, 4.44, 4.09,
D.sub.2O--CD.sub.3OD 1242, 1096 3.95-3.54, 1.60, 1.24, 0.87
Compound 28 3432, 2932, 2860, 1466, 4.10, 3.80-
D.sub.2O--CD.sub.3OD 1090, 978 3.22, 1.48, 1.14, 0.75 Compounds
3380, 2928, 2860, 1676, 3.96-3.49, D.sub.2O--CD.sub.3OD 31-A &
31-B 1642, 1470, 1082, 936 3.23, 1.90, 1.74-1.14, 0.88 Compound 32
3368, 2932, 2860, 1682, 3.96-3.22, D.sub.2O--CD.sub.3OD 1646, 1470,
1082, 974 1.93, 1.72, 1.31, 0.92 Compound 33 3372, 2932, 2860,
1682, 3.91-3.24, D.sub.2O--CD.sub.3OD 1644, 1470, 1058, 924 1.92,
1.65, 1.29, 0.91 Compound 34 3372, 2932, 2860, 1682, 3.91-3.24,
D.sub.2O--CD.sub.3OD 1638, 1472, 1054, 926 1.92, 1.67, 1.30, 0.92
Compound 35 3416, 2932, 2860, 1682, 3.97-3.28, D.sub.2O--CD.sub.3OD
1648, 1470, 1078, 930 1.58, 1.28, 0.87 Compound 36 3396, 2932,
2860, 1684, 3.71-2.96, D.sub.2O 1634, 1470, 1062, 972 1.67, 1.44,
1.06, 0.65 Compound 37 3376, 2924, 2856, 1678, 3.67-2.90, D.sub.2O
1636, 1472, 1054, 928 1.67, 1.44- 1.33, 1.02, 0.61 Compound 38
3372, 2924, 2856, 1682, 3.73-3.00, D.sub.2O 1636, 1472, 1054, 928
1.67, 1.48- 1.40, 1.07, 0.66 Compound 39 3368, 2924, 2856, 1680,
3.77-3.01, D.sub.2O 1636, 1472, 1058, 920 1.70, 1.43, 1.10, 0.66
Compound 40 3400, 2932, 2860, 1678, 5.11, 3.74- D.sub.2O 1636,
1470, 1054, 974 3.02, 1.68, 1.37, 1.07, 0.67 Compound 41 3368,
2932, 2860, 1678, 3.96-3.27, CDCl.sub.3 1642, 1470, 1089, 974 1.55,
1.26, 0.88 Compound 41 3384, 2928, 2860, 1682, 3.96-3.28,
CDCl.sub.3 1646, 1470, 1070, 974 1.55, 1.26, 0.88
Example 1
[0087] 1) After type I collagen ("Cellmatrix Type I-A", Nitta
Gelatin), "MCDB 153 medium" (Sigma Chemical Co.), 20 mM HEPES (Wako
Pure Chemical Industries) and purified water were thoroughly mixed
under ice cooling, 500 .mu.L per well were added to a 24-well plate
(Falcon), followed by warming at 37.degree. C. in an incubator to
effect gelation. Using MCDB 153 medium, 1 mL aliquots of
keratinocytes ("NHEK 6306", Clonetics) were seeded at
2.times.10.sup.4 cells/cm.sup.2 onto the collagen gels,
respectively. Subsequent to incubation for 24 hours, the collagen
gels were peeled off with a pipette tip from the culture dishes.
Shortly after that, test substances prepared to a concentration as
high as 100 times the final concentration were added 10 .mu.L by 10
.mu.L. Upon elapsed time of 1 hour after the addition, the gels
were photographed using a "Minolta .alpha.707-si Camera" with "50
Macrolens". Subsequent to development of the pictures, contracted
rings were copied onto OHP sheets, the areas inside the contracted
rings were determined by image analysis software, "Image-Pro PLUS"
(Media Cybanetics, Inc.), and contraction ratios (%) were
calculated supposing that the contraction ratio (%) of a control
(gel peeling alone) was 100. The results are presented in Table
2.
2 TABLE 2 Contraction Test substance Concentration (.mu.M) ratio
(%) Compound 8 50 77.0 Compound 9 50 62.3 Compound 14 50 90.0
Compound 18 50 90.1 Compound 23 10 60.7 Compound 24 10 84.9
Compound 25 10 88.0 Compound 26 1 73.5 Compound 27 10 67.0 Compound
28 10 48.3 Compound 29 10 53.3 Compound 30 10 56.8 Compound 31-A 10
56.6 Compound 31-B 10 56.7 Compound 32 10 52.2 Compound 33 10 63.4
Compound 34 10 67.3 Compound 35 10 66.9 Compound 36 10 71.3
Compound 37 10 63.3 Compound 38 10 81.4 Compound 39 10 70.2
Compound 40 10 63.0 Compound 41 10 87.3 Compound 42 10 87.7
[0088] As evident from Table 2, the compounds of the formula (1)
have excellent keratinocyte contracting effect.
Example 2
[0089] Three of New Zealand white rabbits (male, about 2.5 kg)
which ear skin pores were conspicuous were used. A 2% solution of
Compound 9 (solvent: ethanol) was applied onto the left ear of each
rabbit, and the solvent was applied onto the right ear of the
rabbit as a control site, each on the inner side of the ala, twice
a day, 150 .mu.L each time.
[0090] Upon elapsed time of 8 weeks after the initiation of the
application, the skin was collected, and the size of skin pores was
measured by image analysis. Described specifically, each rabbit was
sacrificed and then, his ears were collected. A scalpel was
inserted into each ear sample around the applied site, and the skin
was peeled off above the cartilage. At that time, care was
exercised to avoid stretching of the skin. The skin was spread over
a cork board and then, subjected to biopsy with a punch of 6 mm in
diameter to collect the skin from six (6) locations on each ear.
The collection was conducted such that skin samples were obtained
from the same locations on both the left and right ears. The skin
samples collected by punch biopsy were magnified 40-fold by a
videomicroscope (manufactured by HIROX CO., LTD.) while exercising
care to avoid drying, and their images were captured. Measurement
of skin pores from the captured images was conducted using the
image analysis software, "Image-Pro PLUS" (Media Cybanetics, Inc.).
Namely, each captured image was converted into an 8-bit gray scale
image, which was then binarized using 100 as a threshold. From
image elements still remaining after the processing, image elements
other than skin pores were eliminated. On the image, the areas of
the individual skin pores were measured, so that the skin pore area
on each punched skin sample was calculated. An average of the skin
pore areas on the six punched skin samples was recorded as the size
of skin pores on the corresponding ear sample of the corresponding
rabbit.
[0091] As a result of calculation of the areas of skin pores on the
applied sites of the individual ear samples, the sites applied with
Compound 9 had a skin pore area of 0.015 mm.sup.2 as opposed to
0.022 mm.sup.2, the skin pore area of the control sites, so that
the sites applied with Compound 9 were found to be about 30%
smaller in skin pore area than the control sites. Based on a
significance test conducted by the paired comparison testing
method, the test result was determined to be significant with a
risk factor of not greater than 5%. In addition, the remaining
compounds obtained in the above-described
Production Examples also exhibited skin pore contracting effect
like Compound 9.
Example 3
[0092] Measurement of Collagen Gel Tightening Promoting Ability
[0093] Measurement was conducted on the ability to promote the
tightening of a fibroblast-embedded collagen gel as a dermis model.
The collagen gel was prepared following the procedure reported in a
publication [J. Cell Science, 102, 315 (1992) or J. Invest.
Dermatol., 93, 792 (1989)]. Described specifically, a solution of
HEPES (250 mM) in a 0.05 N sodium hydroxide solution, a 5-fold
concentrate of DMEM ("GIBCO DMEM", low glucose), FCS (2%, Fetal
Calf Serum) and purified water were added under ice cooling to a
collagen gel solution (product of Nitta Gelatin Inc., "type 1-A"
(3.0 mg/mL, pH=3)), and finally, a suspension of human skin
fibroblasts (derived from a human fore skin) was added. After the
resulting mixture was thoroughly stirred to eliminate bubbles, 600
.mu.L per well was added to 24-well dishes, followed by immediate
warming at 37.degree. C. in an incubator to effect gelation. Three
to four hours later, 1 mL of serum-free DMEM medium was added to
each of the wells, and the gels were separated at peripheries
thereof from the corresponding dishes and were brought into a
floating state. Eighteen hours after that, the medium was replaced
with serum-free DMEM media which contained 100 to 10 .mu.M of test
substances, respectively, and incubation was conducted further for
48 hours.
[0094] Volume measurement of the gels was conducted by a weight
measuring method similar to that reported in the publication [J.
Cell Science, 102, 315 (1992)]. Described specifically, subsequent
to immobilization with 10% formalin (4.degree. C., 24 hours), the
surface tension of water was reduced by the addition of Triton X100
(product of Wako Pure Chemical Industries) (1%), and the weights
were measured.
[0095] Measurement results of relative volumes for the respective
compounds as calculated supposing that the volume of the control
was 100% are presented in Table 3.
3 TABLE 3 Compound Concentration (.mu.M) Average gel volume Control
100 Compound 1 10 93 30 85 Compound 2 10 97 30 92 Compound 3 3 86
10 74 30 95 Compound 4 15 96 50 88 Compound 5 15 94 50 83 Compound
6 15 91 50 88 Compound 7 15 94 50 79 Compound 8 15 93 50 77
Compound 31-A 15 94 50 79 Compound 32 15 92 50 75
[0096] As evident from Table 3, it is understood that under the
action of the compounds according to the present invention, the
collagen gels were reduced in volume and the tightening of the
collagen gels was promoted.
Example 4
[0097] Evaluation of Rat Skin Elasticity Improving (Tightening)
Effect
[0098] Onto the entire dorsal skins of HR rats (WBN/ILA-HT, 7 weeks
old), 2% solutions of Compounds 1 and 4 (solvent: 10% ethanol) were
applied in the form of spray, respectively, once or twice a day, 7
to 8 times a week in total, in an amount of 0.7 mL each time. As a
control, 10% ethanol solution was used. Two weeks later, the skin
elasticity of the skin at a central dorsal part at a site slightly
rightward of the median line of each HR rat was measured under
Nembutal anesthesia by using a cutometer ("CUTOMETER SEM474",
Courage+Khazaka Electronic GmbH). The measurement was conducted by
setting the suction pressure, suction time and release time at 100
hpa, 5 seconds and 2 seconds, and an instantaneous elastic
displacement Ue, an instantaneous recovery displacement Ur and a
final displacement Uf were recorded. Based on changes in the skin
elasticity, skin tightening effect was determined. Ue is an index
of elasticity, while Uf is an index of softness and malleability.
Both of these values decrease on the face or the like upon aging,
and also decrease when the skin is in a swollen state. Increases in
these values, therefore, can be taken as an indication of a state
that the skin is in a tightened state with its softness,
melleability and elasticity having been increased further. Ur is
also an index of elasticity, and decreases when the skin is in a
saggy state or a swollen state. Similarly, an increase in this
value serves as an indication of a state that the skin is in a
tightened state with its elasticity and tightness having been
increased further. Further, Ur/Uf is also an index of the
elasticity of the skin, and like Ur, decreases when the skin
becomes saggy or is swollen. Moreover, Ur/Uf is known to decrease
upon aging irrespective of the face or body site, and is an
important index of sagginess. The results are presented in Table 4
and Table 5.
4TABLE 4 Skin thickness Compound (mm) Ue Uf Ur Ur/Uf Control 0.835
0.100 0.154 0.698 0.457 Compound 1 0.820 0.113 0.159 0.834
0.540
[0099]
5TABLE 5 Skin thickness Compound (mm) Ue Uf Ur Ur/Uf Control 0.753
0.200 0.248 0.088 0.371 Compound 4 0.725 0.225 0.275 0.109
0.401
[0100] From Table 4 and Table 5, it has been confirmed that
Compounds 1 and 4, when applied, increased the skin elasticity and
exhibited skin tightening effect.
Formulation Example 1 Toilet Water
[0101] A toilet water of the below-described formulation was
prepared by a method known per se in the art.
6 (Ingredients) (wt. %) Compound 1 2.0 Compound 6 0.5 Glycerin 5.0
Dipropylene glycol 4.0 Polyoxyethylene (20) isocetyl ether 1.0
Clove extract 1.0 Orange peel extract 1.0 Hiba arborvitae
(Thujopsis dolabrata 0.5 var. Dorabrata) extract Ethanol 8.0
Preservative q.s. Fragrance q.s. Buffer q.s. Purified water
Balance
Formulation Example 2 Cream (W/O)
[0102] A cream of the below-described formulation was prepared by a
method known per se in the art.
7 (Ingredients) (wt. %) Compound 9 2.0 Compound 7 1.0
Microcrystalline wax 3.0 Lanolin 3.0 Vaseline 5.0 Squalane 9.0
Olive oil 12.0 Sorbitan sesquioleate 3.0 Polyoxyethylene (20)
sorbitan trioleate 3.0 Barley extract 2.0 Placenta extract 1.0
Albutin 1.0 Kojic acid 1.0 Phosphatidylcholine 1.0 Fragrance q.s.
Buffer q.s. Purified water Balance
Formulation Example 3 Cream (O/W)
[0103] A cream of the below-described formulation was prepared by a
method known per se in the art.
8 (Ingredients) (wt. %) Compound 5 2.5 Compound 1 0.3 Hardened
coconut oil 6.0 Stearic acid 3.0 Cetanol 4.0 Vaseline 2.0 Squalane
8.0 Neopentyl glycol dicaprinate 4.0 Polyoxyethylene (20) sorbitan
monostearate 2.3 Glycerin stearate 1.7 Glycerin 3.0 1,3-Butylene
glycol 7.0 Glycyrrhizic acid 1.0 Tocopherol 2.0 Hyaluronic acid 1.0
Dutch mustard extract 3.0 Aloe extract 1.0 Carrot extract 1.0
Preservative q.s. Fragrance q.s. Purified water Balance
Formulation Example 4 Emulsion
[0104] An emulsion of the below-described formulation was prepared
by a method known per se in the art.
9 (Ingredients) (wt. %) Compound 1 1.5 Compound 7 0.3 Palmitic acid
0.5 Olive oil 2.0 Cetanol 1.0 Jojoba oil 5.0 Sodium
monohexadecylphosphate 2.0 Sorbitan monostearate 0.5 Glycerin 15.0
Ethanol 5.0 Ascorbic acid 0.5 Tocopherol nicotinate 1.0 Zingiber
officinale (ginger) root extract 2.0 Ginkgo biloba extract 2.0
Preservative q.s. Fragrance q.s. Purified water Balance
Formulation Example 5 Emulsion
[0105] An emulsion of the below-described formulation was prepared
by a method known per se in the art.
10 (Ingredients) (wt. %) Compound 9 2.0 Compound 3 0.8 Compound 1
1.2 Stearic acid 1.0 Cholesteryl isostearate 2.0 Jojoba oil 4.0
Squalane 8.0 Sorbitan sesquioleate 0.8 Polyoxyethylene (20)
sorbitan monostearate 0.5 1,3-Butylene glycol 5.0 L-Arginine 0.4
Carboxyvinyl polymer 0.2 Carrot extract 1.5 Uncaria Gambir extract
0.5 Corthellus shiitake (mushroom) extract 0.5 Laminaria japonica
extract 0.5 Ceramide 1.0 Preservative q.s. Fragrance q.s. Purified
water Balance
Formulation Example 6 Pack
[0106] A pack of the below-described formulation was prepared by a
method known per se in the art.
11 (Ingredients) (wt. %) Compound 5 3.0 Compound 8 2.0 Polyvinyl
alcohol 14.0 Carboxymethylcellulose sodium 3.0 Xanthan gum 1.0
Glycerin 3.0 1,3-Butylene glycol 2.0 Polyoxyethylene (50)
hydrogenated castor oil 0.5 Japanese angelica root extract 0.5 Whey
extract 2.0 Astragalus sinicus extract 0.5 Sphingosine 0.2
Preservative q.s. Fragrance q.s. Purified water Balance
Formulation Example 7 Toilet Water
[0107] A toilet water of the below-described formulation was
prepared by a method known per se in the art.
12 (Ingredients) (wt. %) Compound 31-A 1.0 Glycerin 5.0
Polyoxyethylene (20) isocetyl ether 0.1 L-Arginine 0.6 Tuberose
polysaccharide solution 10.0 Ethanol 10.0 Preservative q.s.
Fragrance q.s. Buffer q.s. Purified water Balance
Formulation Example 8 Toilet Water
[0108] A toilet water of the below-described formulation was
prepared by a method known per se in the art.
13 (Ingredients) (wt. %) Compound 32 1.0 Glycerin 5.0
Polyoxyethylene (20) isocetyl ether 0.1 L-Arginine 0.6 Tuberose
polysaccharide solution 10.0 Ethanol 10.0 Preservative q.s.
Fragrance q.s. Buffer q.s. Purified water Balance
[0109] Industrial Applicability
[0110] The skin pore tighteners according to the present invention
have excellent effect in tightening skin pores and rendering them
less conspicuous, while the skin elasticity improvers and skin
tighteners according to the present invention have superb effect in
preventing and lessening skin wrinkles and sagging. Accordingly,
they are useful as ordinary cosmetic preparations, as cosmetic
preparations after depilating treatment, and also as cosmetic
preparations after removal of keratotic plugs.
* * * * *