Note: Descriptions are shown in the official language in which they were submitted.
SSD. SJP-7283
1 336688
HAIR COSMETIC COMPOSITION
RAc~GRouND OF THE INVENTION
1. Field of the Invention
The present invention relates to a hair
cosmetic composition especially a hair cosmetic
s composition for preventing dandruff and a loss of hair, .
which contains, as an active component, a diester of
phosphoric acid with ascorbic acid and tocopherol,
having the following general formula (1), and/or a salt
thereof:
CH3
C=O R2 ~ ~ H3 IH3
C--O-- ~-- O~ ~ ~ J (CH2cH2cH2cH)3-cH3
O C-OH OH
L CH R
t I ]
HOH2C-CH-OH
wherein R1 represents H or CH3 and R2
represents H or CH3
The diester of phosphoric acid with ascorbic acid
and tocopherol according to the present invention has a
structure in which two of three hydroxyl groups of
phosphoric acid are esterified by one hydroxyl group
each of ascorbic acid and tocopherol.
2. Description of the Related Art
In general, dandruff comprises exudates of
sebaceous glands, exudates of sweat glands, and
substances exfoliated and peeled from epidermal tissue
layers, and usually dandruff is formed by an
exacerbation of a secretion in sebaceous glands and the
like. It is considered that, if the skin is infected
with bacteria or yeasts, the generation of dandruff is
greatly increased and a loss of hair occurs, and
accordingly, hair cosmetics comprising an antibacterial
agent or fungicide have been used as a hair cosmetic
' ~ ~
-- 1 336688
for preventing dandruff or a loss of hair. Some of
these antibacterial agents and fungicides irritate the
skin and are disadvantageous from the view point of the
safety of a human body. Furthermore, it has been
pointed out that if a cosmetic comprising an
antibacterial agent or fungicide is used continuously
day after day, a delicate balance among skin bacteria is
destroyed and an unpreferable ecological condition is
brought into existence. For example, zinc pyrithion
(ZPT), considered to be most effective among
conventional dandruff-preventing agents, falls under the
category of an "antibacterial agent and it is
considered that an excessive use of this agent should be
avoided.
Accordingly, there is an urgent need to prevent
dandruff or a loss of hair without using an
antibacterial agent or fungicide, and intensive research
is underway into the development of safe substances
having an effective dandruff-controlling action without
an antibacterial or fungicidal action.
As substances exerting a dandruff-controlling
effect not based on an antibacterial or fungicidal
action, there have been reported an ~-tocopherol/vitamin
A acid ester (Japanese Unex~mined Patent Publication
No. 51-73137) and a vitamin E/nicontinic acid ester.
(German Patent No. 2,301,585 and German Patent
No. 2,301,660).
These conventional tocopherol esters, however, are
not stable on the skin and do not have a long-term
dandruff-control effect. Further, since the tocopherol
esters are insoluble in water, they are defective in
that oily precipitates are formed in certain forms of
cosmetics. Furthermore, to incorporate the necessary
amounts of these esters, large quantities of surface
active agents must be used, and thus the use of these
tocopherol esters becomes expensive.
SUMMARY OF THE INVENTION
1 336688
- 3 -
Accordingly, the objects of the present invention -
are to eliminate the above-mentioned disadvantages of
the prior art and to provide a hair cosmetic
composition having an improved dandruff-preventing
effect, safety, and stability.
Other advantages of the present invention will be
apparent from the following description.
The present invention provides the use of an anti-
dandruff effective amount of a hair cosmetic
composition to treat a patient suffering from dandruff
or hair loss due to dandruff, said composition
comprising (i) as an active component, about 0.01 to
about 10~ by weight of at least one component selected
from the group consisting of diesters of phosphoric
acids with ascorbic acid and tocopherol, having the
formula [I], and salts thereof:
CH3
2 0 C=O O R2~1,0~H3 CI H3
C--O--I--O ~ jl (CH2CH2CH2CH)3CH3
O C-OH OH
L CH
~ I 3
2 5 HOH2C-CH-OH
wherein Rl represents H or CH3 and R2 represents H or
CH3; and (ii) a carrier.
- 3a -
..,
, ~
r
1 336688
- 3a -
DESCRIPTION OF THE PREFERRED ENBODIMENTS
The present inventors tested various tocopherol
derivatives to determine their dandruff-preventing
effects, with a view to overcoming the foregoing defects
of the conventional tocopherol esters, and as a result,
found that a diester of phosphoric acid with ascorbic
acid and tocopherol and/or a salt thereof has a
remarkable effect and an improved safety and stability.
The present invention is based on this finding.
Any of ~ -, 7- and ~-tocopherols can be used as
the tocopherol constituting the diester of phosphoric
acid with ascorbic acid and tocopherol, and the
relationship between the type of the tocopherol and R
1 336688
-- 4
and R2 in the above general formula is as described
below.
Type R1 R2
CH3 CH3
~ CH3 H
7 H CH3
~ H H
The diester of phosphoric acid with ascorbic acid
and tocopherol and its salt used in the present
invention can be prepared, for example, by the following
process disclosed in Japanese Unexamined Patent
Publication No. 59-219295 (i.e., U.S. Patent
No. 4564686). More specifically, tocopherol is reacted
with a halogenophosphorylating agent. This reaction
proceeds rapidly in a non-reactive solvent in the
presence of a deacidifying agent, and the obtained
product is reacted with an ascorbic acid in which the
hydroxyl groups in the 5- and 6-positions are protected
by protecting groups. This reaction proceeds in a
solvent such as tetrahydrofuran, in the presence of a
deacidifying agent, and thus the protecting groups are
eliminated, whereby the diester of phosphoric acid with
ascorbic acid and tocopherol according to the present
invention is prepared.
The phosphoric acid diester of the present
invention can be used in the form of either a free acid
or a salt. As the salt, there can be mentioned an
organic amine salt and an inorganic salt. As the
organic amine salt, there can be mentioned an
`- 1 336688
-- 5
aminomethylpropanol salt, an aminohydroxylmethyl-
propane-diol salt, an aminomethylpropane-diol salt, an
isopropanolamine salt, a monoethanolamine salt, a
diethanolamine salt, a triethanolamine salt, a
morpholine salt, a glucosamine salt, and a diisopro-
panolamine salt, and as the inorganic salt, there can be
mentioned a sodium salt, a potassium salt, a lithium
salt, a calcium salt, and a magnesium salt. Of these
salts, for example, the sodium salt and potassium salt
are soluble in water but the calcium salt, for example,
is insoluble in water. Therefore, an appropriate salt
can be selected according to the intended object.
The phosphoric acid diester and its salt can be
freely dissolved in water or an oil directly or after
dissolving it in water, an alcohol or an aqueous
solution of an alcohol, and therefore, the application
range is broader than that of tocopherol or the like.
In the present invention, at least one member
selected from the group consisting of diesters of
phosphoric acid with ascorbic acid and tocopherol and
salts thereof is used. The diester of phosphoric acid
or its salt can be incorporated in an amount of 0.01
to 10% by weight (all of "%" given hereinafter are by
weight), preferably 0.05 to 2%, based on the total
amount of the hair cosmetic composition. If the amount
is smaller than 0.01%, the dandruff-preventing effect is
poor, and even if the amount is larger than 10%, a
further increase of the effect cannot be expected.
By the hair cosmetic referred to in the present
invention is meant a variety of cosmetics to be applied
to the hair and skin of the head, for example, hair
tonics, hair liquids, head skin milky lotions, hair
creams, hair shampoos, and hair rinses.
Other hair-treating agents such as
dandruff-preventing agents and loss of hair-preventing
agents, and usual components, can be incorporated into
the hair cosmetic composition of the present invention.
- 1 336688
-- 6
For example, as the other dandruff-preventing
agent, there can be mentioned ZPT, TCC, hinokitiol,
~-tocopherol/vitamin A acid ester, vitamin E/nicotinic
acid ester, vitamin E/acetic acid ester, selenium
sulfide, thioxolone, sulfur, salicylic acid, resorcinol,
hexachlorophene, tetrachlorosalicylanilid, benzalconium
chloride, and quaternary ammonium salts such as
octadecyltrimethyl ammonium chloride and
hexadecyldimethyl-benzyl ammonium chloride. Further,
any other forms of hair-treating agents can be used. As
other ingredients to be incorporated in the hair
cosmetic of the present invention, there can be
mentioned inorganic powders such as talc, kaolin,
sericite, white mica, gold mica, red mica, black mica,
lithia mica, vermiculite, synthetic mica, magnesium
carbonate, calcium silicate, aluminum silicate, barium
silicate, barium sulfate, strontium silicate, metal
tungstates, silica, zeolites, boron nitride, barium
sulfate, calcined calcium sulfate (calcined gypsum),
calcium phosphate, fluorine apatite, powdery ceramics
and metal soaps (such as zinc myristate, calcium
palmitate and aluminum stearate), organic powders such
as polyamide resin powder (nylon powder), polyethylene
powder, polymethyl methacrylate, polystyrene powder,
styrene/acrylic acid copolymer resin powder,
benzoguanamine resin powder, polytetrafluoroethylene
powder and cellulose powder, inorganic white pigments
such as titanium dioxide and zinc oxide, inorganic red
pigments such as iron oxide (red iron oxide) and iron
titanate, inorganic brown pigments such as 7-iron oxide,
inorganic yellow pigments such as yellow iron oxide and
ochre, inorganic black pigments such as black iron
oxide, carbon black, low titanium oxide antinium
oxynitride, inorganic violet pigments such as Mango
Violet and Cobalt Violet, inorganic green pigments such
as chromium oxide, chromium hydroxide, and cobalt
titanate, inorganic blue pigments such as ultramarine
- 1 336688
-- 7
and prussian blue, pearl pigments such as titanium
oxide-coated mica, bismuth oxychloride, titanium
oxide-coated bismuth oxychloride, titanium oxide-coated
talc, colored titanium oxide-coated mica, and fish
5 scale, metal powder pigments such as aluminum powder and
copper powder, organic dyes and pigments such as
Red 201, Red 202, Red 204, Red 205, Red 220, Red 226,
Red 228, Red 405, Orange 203, Orange 204, Yellow 205,
Yellow 401, and Blue 404, zirconium-, barium-, and
aluminum-chelate organic pigments such as Red 3,
Red 104, Red 106, Red 227, Red 230, Red 401, Red 505,
Orange 205, Yellow 4, Yellow 5, Yellow 202, Yellow 203,
Green 3, and Blue 1, natural colors such as chlorophyll,
~-carotene, and calsamine, animal-and plant-derived oils
such as avocado oil, camellia oil, academia nut oil,
corn oil, olive oil, evening primrose oil, rape oil,
yolk oil, sesame oil, persic oil, wheat germ oil,
sasaqua oil, castor oil, hardened castor oil, linseed
oil, safflower oil, sunflower oil, cotton seed oil,
soybean oil, peanut oil, tea seed oil, nutmeg oil, rice
bran oil, chinese tung oil, Japanese tung oil, jojoba
oil, germ oil, sugar cane wax, cacao fat, coconut oil,
hardened coconut oil, turtle oil, mink oil, squalene,
squalane, orange raffinate, beef tallow, horse tallow,
sheep tallow, pig tallow, beef cattle bone fat, beef
cattle leg fat, hardened beef tallow, wood wax, bees
wax, candelilla wax, cotton wax, carnauba wax, bayberry
wax, insect wax, spermaceti, bran wax, kapok wax,
lanolin, lanolin alcohol, hydrous lanolin, jojoba wax,
shellac, POE lanolin alcohol acetate, POE cholesterol
ether, lanolin fatty acid polyethylene, and POE
hydrogenated lanolin alcohol ether,
microorganism-derived oils such as oils produced by
microorganisms belonging to the genus Mortierella,
mineral-derived oils such as liquid paraffin, ozocerite,
pristane, ceresine, vaseline and micro-crystalline wax,
higher alcohols such as capryl alcohol, lauryl alcohol,
_ - 8 - l 3 3 6 6 8 8
cetyl alcohol, stearyl alcohol, arachidic alcohol,
behenyl alcohol, oleyl alcohol, cetostearyl alchol,
monostearyl glyceryl ether (patchouli oil),
2-decyltetradecanol, 2-hexyldecanol, 2-hexyldodecanol,
2-octyldodecanol, cholesterol, phytosterol and
isostearyl alcohol, higher fatty acids such as caprylic
acid, lauric acid, myristic acid, palmitic acid, stearic
acid, behenic acid (behenine), 12-hydroxystearic acid,
undecylenic acid, lanoline fatty acid, isostearic acid,
linoleic acid, oleic acid, ricinoleic acid, arachidic
acid, arachidonic acid, and eicosapentaenoic acid, ester
oils such as isopropyl myristate, cetyl octanoate,
octyldodecyl myristate, isopropyl palmitate, butyl
stearate, hexyl laurate, myristyl myristate, decyl
oleate, hexyldecyl dimethyloctanoate, cetyl lactate,
myristyl lactate, lanolin acetate, isostearyl stearate,
isocetyl isostearate, cholesteryl 12-hydroxystearate,
ethylene glycol di-2-ethylhexanoate, dipentaerythritol
fatty acid esters, N-alkylglycol nonoisostearate,
neopentyl glycol dicaprane, diisostearyl malate,
glyceryl di-2-heptylundecanoate, trimethylol-propane
tri-2-ethylhexanoate, trimethylol-propane
triisostearate, pentaerythritol tetra-2-ethylhexanoate,
glyceryl tri-2-ethylhexanoate trimethylol-propane
triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl
palmitate, glyceryl trimyristate, glyceryl trioctanoate,
glyceryl triisopalmitate, glyceryl
tri-2-heptylundecanoate, methyl castor oil fatty acid
ester, lanoline alcohol acetate, isopropyl lanoline
fatty acid ester, oleyl oleate, glyceryl triacetate,
2-butylundecyl palmitate, diisobutyl adipate,
2-octyldecyl N-lauroyl-L-glutamate, di-2-heptylundecyl
adipate, ethyl laurate, di-2-ethylhexyl sebacate,
2-hexyldecyl myristate, 2-hexyldec, l-palmitate,
diisopropyl sebacate and 2-ethylhexyl succinate PABA
type ultraviolet absorbants such as p-aminobensoic acid
(hereinafter referred to as "PABA" ), PABA butyl ester,
- 9 1 336688
PABA glyceryl ester, N,N-dipropoxy PABA ethyl ester,
N,N-diethoxy PABA ethyl ester, N,N-dimethyl PABA ethyl
ester, N,N-dimethyl PABA amyl ester and N,N-dimethyl
PABA iso-octyl ester, salicylic acid type ultraviolet
absorbers such as amyl salicylate, menthyl salicylate,
homomentyl salicylate, octyl salicylate, phenyl
salicylate, benzyl salicylate, dipropylene glycol
salcylate, ethylene glycol salicylate and p-isopropanol
phenyl salicylate, cinn~mic acid type ultraviolet
1.0 absorbants such as octyl cinn~m~te, ethyl-4-isopropyl
cinnamate, methyl-2,5-diisopropyl cinn~te,
ethyl-2,4-diisopropyl cinn~mAte, methyl-2,4-diisopropyl
cinnamate, propyl p-methoxycinn~m~te~ isopropyl
p-methoxycinn~m~te, isoamyl p-methoxycinn~m~te, octyl
p-methoxycinnamate (2-ethylhexyl p-methoxycinn~m~te),
2-ethoxyethyl p-methoxycinn~m~te, cyclohexyl
p-methoxyci~n~m~te, ethyl-~-cyano-~-phenyl cinnamate,
2-ethylhexyl-~-cyano-~-phenyl ci~n~m~te and
mono-2-ethylh~x~noyl di-p-methoxycinnamoylglycerol,
benzophenone type ultraviolet absorbants such as
- 2,4-hydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzo-
phenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone,
2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-
methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methyl-
benzophenone, 2-hydroxy-4-benzophenone-5-sulfonate,
4-phenylbenzophenone, 2-hydroxy-4-n-octoxybenzophenone,
2-hydroxy-4-chlorobenzophenone and 2,2'-dihydroxy-4,4'-
methoxybenzophenone-3,3'-disulfonate, ultraviolet
absorbants such as 3-(4'methylbenzylidene)-d,~-camphor,
3-benzylidene-d,~-camphor, urocanic acid, ethyl
urocanate, 2-phenyl-5-methylbenzoxazole, 2-phenyl-5-
methylbenzoxazole-5-sulfonic acid, 2-(2'-hydroxy-S-
methylphenyl)benzotriazole, 2-(2'-hydroxy-5-t-octyl-
phenyl)benzotriazole, dibenzalzine, dianisoylmethane,
4-methoxy-4'-t-butylbenzoylmethane, 5-(3,3-dimethyl-
2-norbornylidene)-3-pentan-2-one and guanine,
moisture-preserving agents such as polyethylene glycol,
- I 336688
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polyethylene glycol, dipropylene glycol, glycerol,
1,3-butylene glycol, xylytol, sorbitol, maltitol,
mucopolysaccharides and salts thereof tchondroitin
sulfuric acid (salt), hyaluronic acid (salt), charonin
5 sulfuric acid, heparin sulfuric acid and keratosulfuric
acid], proteoglycans (proteokeratosulfuric acid and
proteochondroitin sulfuric acid), (athero)collagen,
soluble collagen, cholesteryl-12-hydroxystearate, lactic
acid (salt), bile acid (salt), pyrrolidone-carboxylic
acid (salt), polyglycerol (EO) PO adduct and glucose EO
adduct, organic thickening agents such as gum arabic
corageenan, tragacanth gum, carob gum, quince seed
(marmello) casein, dextrin, gelatin, sodium pectate,
sodium alginase, methyl cellulose, ethyl cellulose,
carboxymethyl cellulose hydroxyethyl cellulose,
hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl
butyral, polyvinyl pyrrolidone, carboxyvinyl polymer,
locust bean gum, gua gum, tamarind gum, dialkyldimethyl
ammonium sulfate cellulose, xanthane gum, and hyaluronic
acid (salt), inorganic thickening agents such as
montmorillonite, saponite and hectorite, organically
modified mineral thickening agents such as thickening
agents obtained by modifying these inorganic thickening
agents with quaternary ammonium salt type cationic
activators, non-ionic activators, silicone type
activators or the like, organic solvents such as
acetone, toluene, butyl acetate and ethyl acetate,
plasticizers such as acetyltriethyl citrate and
acetyltributyl acetate, antioxidants such as
butylhydroxytoluene (BHT), butylhydroxyanisole (BHA),
tocopherol, catechin, epigallocatechin,
epigallocathechin gallate, green tea tannin, propyl
gallate, phytic acid and an ester of phosphoric acid
with tocopherol and ascorbic acid, antibacterial
antiseptic agents such as benzoic acid (salt), salicylic
acid (salt), sorbic acid (salt), dehydroacetic acid
(salt), alkyl p-hydroxybenzoates (ethyl paraben and
11 1 336688
butyl paraben) and hexachlorophene, neutral amino acids
such as glycine, alanine, valine, leucine, isoleucine,
serine, threonine, phenylalanine, tyrosine, tryptophane,
cystine, cysteine, methionine, proline, hydroxyproline
and DOPA, acidic amino acids and alkali metal salts
thereof such as aspartic acid, glutamic acid,
asparagine, glutamine and taurine, organic amine salts
and basic amino acid salts, basic amino acids and
hydrochlorides thereof such as alginine, hystidine and
lysine, acylsarcosine salts (for example, sodium
lauroylsarcosine), acylaminoacid salts (for example,
sodium lauroylglutamate and sodium acyl ~-alanine),
glutathione, organic acids such as citric acid, malic
acid, tartaric acid and lactic acid, vitamin A and its
derivatives, vitamins B such as vitamin B6
hydrochloride, vitamin B6 tripalmitate, vitamin B6
dioctanoate, vitamin B2 ~ derivatives thereof,
vitamin B12 , vitamin B15 and derivatives thereof,
vit~mins C such as ascorbic acid, sulfate ascorbate, an
ascorbic acid ester of phosphoric acid and ascorbic acid
dipalmitate, vit~inR E such as ~-tocopherol,
~-tocopherol, 7-tocopherol, vitamine E acetate and
vitamin E nicotinate, other vitamins such as vitamin H,
pantothenic acid and panthetine, various medicines such
as nicotinic acid amide, benzyl nicotinate, 7-oyzanole,
allantoin, glycyrrhetinic acid and derivative thereof,
hinokitiol, musdine, bisabolol, eucalyptol, phytosterol,
thymol, inositol, saponins (saikosaponin, carrot saponin
and luffa saponin~, tannins (gallot~nnins such as tannic
acid and catechins such as catechin, epigallocatechin,
epigallocatechin gallate and epicatechin gallate),
pantothenyl ethyl ether, ethynylestradiol and placenta
extract, natural extracts obtained by extracting
licorice, paprika, Isodon japonicus, Isodon
trichocarpus, Inula japonica, Bixa orellana, sorrel,
Sophora anqustifolia, Cinnamonum camphora, Nuphar
japonicum, Houttuynia cordota, iris, Japanese
~ 1 336688
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honeysuckle, celery, geranium, turmeric, dead nettle,
tea (green tea and black tea), orange, sage, Hedera
helix, Ruscus, milfoil, mistletoe, mallow, Cnidium
officinale, Japanese green gentian, thyme, clove, Citrus
unshiu, Anqelica acutilaba, pot marigold, orange peel,
carrot, onion, wild rose, birch, parsley, gentian, mint
fennel, field horsetail, saffron, mustard, soapwort,
butcher's broom, grape, ivy, luffa, nettle, pipal, hop,
pepper tree, Cortinellus shiitake, horse chestnut,
Menyanthes trifoliata, Sapindus mukurossi, melisse,
peach, eucalyptus, parsley, Rehm~nnia qlutinosa,
lithospermum root, creeping saxifrage arnica, lily,
mugwort, beefsteak plant, peony, rosemary, lemon,
ginger, rosa fruit, burnet, white birch, raspberry,
Scutellaria baicalenis, aloe, cucumber, burdock, Cape
jasmine, phellodendron, Japanese coptis, gambir-catechu,
hydrangea leaves, Zizyphus juiuba var. inermis, Davallia
mariessi, ChamaecYParis pisifera, Guinea pepper, Poria
cocos, polypore, Polyporus umbellatus, brachet funqus,
oyster, CrPtoPhYta and Rhodophyta, with organic
solvents, alcohols, polyhydric alcohols, water and
aqueous alcohols, and non-ionic surface active agents,
cationic surface active agents, anionic surface active
agents, amphoteric surface active agents, perfumes,
water, and alcohols.
The hair cosmetic composition according to the
present invention has the following advantages.
(a) The diester of phosphoric acid becomes
water-soluble or oil-soluble according to the kind of
salt, and the diester can be incorporated into any
product regardless of the form thereof.
(b) The compound according to the present
invention has an excellent stability on the skin and is
very safe.
It is considered that the reason why the hair
cosmetic composition of the present invention has an
effective dandruff-preventing action and a loss of
- 1 336688 - 13 -
hair-preventing action is that the metabolic reaction of
the head skin texture is appropriately adjusted and a
formation of a peroxide lipid on the head skin is
inhibited.
Example
The present invention will now be further
illustrated by, but is by no means limited to, the
following Examples, wherein all percentages in the
composition are expressed on a weight basis unless
otherwise noted.
Preparation Example 1
Preparation of potassium L-ascorbic DL-~-tocopherol
phosphate
In 50 ml of benzene was dissolved 6.12 of
phosphorus oxytrichloride, and a mixed solution of 8.6 g
(0.02 mole) of DL-~-tocopherol and 9.5 g of pyridine in
50 ml of benzene was added dropwise to the above
solution while stirring. After termination of the
dropwise addition, the mixture was stirred for another
3 hours, the precipitated pyridine hydrochloride was
removed by filtration, the filtrate was concentrated
under a reduced pressure, and 30 ml of benzene was added
to the residual oil.
Separately, 5.2 g (0.024 mole) of
5,6-isopropylideneascorbic acid obtained by acetonation
of L-ascorbic acid and 3.2 g of pyridine were dissolved
in 120 ml of tetrahydrofuran. The above benzene
solution was added dropwise to the tetrahydrofuran
solution while stirring, and after termination of the
dropwise addition, stirring was conducted for about
another 1 hour. The precipitated pyridine hydrochloride
was removed by filtration, and the solvent was removed
from the filtrate by distillation under a reduced
pressure. The obtained oil was dissolved in 30 ml of
ethyl alcohol, 150 ml of lN hydrochloric acid was added
to the solution, and the mixture was heated and refluxed
for about 20 minutes, cooled, extracted with ethyl
1 336688
- 14 -
acetate, and dried with anhydrous sodium sulfate. Ethyl
acetate was removed by distillation, and a crude free
acid was obtained as the residue.
This crude free acid was dissolved in about 100 ml
of ethyl alcohol, and a solution of potassium hydroxide
in ethyl alcohol was gradually dropped into the above
solution until the pH value of the solution became
neutral, whereby a slightly brownish-white crystal was
precipitated. The crystal was recovered by filtration
and recrystallized from water ethyl alcohol-acetone to
obtain 7.5 g of a white powdery crystal.
Melting point:
Carbonization gradually began at about 210C.
Ultraviolet absorption spectrum (W):
A m~Ximum absorption appeared at about 257 nm.
Silica gel thin layer chromatograph:
Rf = 0.81 (ethyl alcohol/acetone/water =
10/4/1)
Elementary analysis values as C35H55C1oPK2.H2O:
Calculated: C = 55.09%, H = 7.5%
Found: C = 55.32~, H = 7.65%
Preparation Example 2
Preparation of sodium L-ascorbic DL-~-tocopherol
phosphate
In 30 ml of water was dissolved 5 g of potassium
L-ascorbic DL-~-tocopherol phosphate obtained in
Preparation Example 1, and the solution was made acidic
by an addition of hydrochloric acid and extracted with
ethyl acetate. Ethyl acetate was removed from the
extract by distillation to obtain L-ascorbic
DL-~-tocopherol phosphate in the form of a free acid (W
absorption spectrum appeared at 285 nm in water). The
free acid was dissolved in ethyl alcohol, and a 30%
solution of sodium hydroxide was gradually added to the
solution until the solution became neutral, whereby a
white crystal was obtained. The white crystal was
recovered by filtration, washed with ethyl alcohol, and
- 1 336688
- 15 -
dried to obtain about 4 g of the intended salt.
Elementary analysis values as C35HS5010Na2-H20:
Calculated: C = 57.52%, H = 7.86%
Found: C = 57.65%, H = 7.98%
Experimental Example 1
This Example illustrates the dandruff-preventing
effect and the loss of hair effect of the compound of
the present invention.
To 75 g of ethanol were gradually added 0.2 g of
1~ sodium ascorbic ~-tocopherol phosphate (Preparation
Example 2), 0.2 g of polyoxyethylene (8 moles) oleyl
alcohol ether, 24.6 g of purified water, a slight amount
of Yellow 1, and a slight amount of a perfume to prepare
a hair tonic sample (hereinafter referred to as
"phosphoric acid diester-incorporated hair tonic).
Similarly, a hair tonic different from the above hair
tonic in that the diester of phosphoric acid was not
added (water was added instead) was prepared
(hereinafter referred to as "diester-free hair tonic").
Separately, a shampoo comprising 25% of
triethanolamine lauroylpolyoxyethylene (3 moles) sulfate
(40% aqueous solution), 1% of a carboxyvinyl polymer, 3%
of glycerol and 1% of zinc pyrithione (ZPT) and purified
water in an amount such that the entire amount was 100%
was prepared (hereinafter referred to as
"ZPT-incorporated shampoo"). Similarly, a shampoo
comprising 1% of sodium ascorbic acid ~-tocopherol
phosphate instead of ZPT (hereinafter referred to as
"phosphoric acid diester-incorporated shampoo") and a
shampoo not cont~ining ZPT or sodium ascorbic acid
~-tocopherol phosphate (water was added instead)
(hereinafter referred to as "chemical-free shampoo")
were prepared.
Nine men 18 to 55 years old and having scurf on the
head were selected as the subjects of the experiment.
At the control stage, the hair of all of the men was
washed with the chemical-free shampoo and then treated
1 336688
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with the diester-free hair tonic, and after two days,
the accumulated dandruff was collected. This operation
was conducted twice a week for one month (eight times in
total). The dandruff was collected by suction from the
head skin, using a suction device. The amount of the
protein in the collected dandruff was measured by the
micro-Rjeldahl method and the average protein amount Pc
per operation was determined with respect to each
subject. Then, 13 subjects were divided into three
groups (S subjects, 4 subjects and 4 subjects). The
hair of the 5 subjects of the first group was washed
with the phosphoric acid diester-incorporated shampoo
and then treated with the phosphoric acid
diester-incorporated hair tonic, and the hair of the
4 subjects of the second group was washed with the
ZPT-incorporated shampoo and treated with the phosphoric
acid diester-incorporated hair tonic. The hair of the
4 subjects of the third group was washed with the
ZPT-incorporated shampoo and then treated with the
diester-free hair tonic. The accumulated dandruff was
collected from each group after 2 days, and then twice a
week for 1 month (8 times in total). The protein
quantity in the dandruff collected during this period
(experimental period) was measured in the same manner
for in the control, and the average protein amount Ps
per operation was determined with respect to each
subject.
The dandruff reduction ratio (%) during the
experimental period was calculated according to the
formula (Pc - Ps)/Ps x 100. The results are shown in
Table 1.
- 17 _ l 336 688
Table 1
First Group Second Group Third Group
(phosphoric acid di- (ZPT-incorporated (ZPT-incorporated
ester-incorporated shampoo and phos- shampoo and di-
shampoo and hair phoric acid di- ester-free hair
tonic) ester-incorporated tonic)
hair tonic)
Dandruff . Dandruff . Dandruff
Subject Sub~ect Sub~ect
control control control
No. ratio (%)No. ratio (~)No. ratio (%)
1 34.71 1 29.01 1 21.19
2 39.81 2 28.16 2 26.01
3 41.32 3 29.91 3 20.91
4 37.92 4 19.81 4 18.22
37.11
average 38.17average 26.72 average 21.S8
From the shown in Table 1 results, it can be seen
that the sodium ascorbic acid ~-tocopherol
phosphate-incorporated shampoo has an excellent
dandruff-preventing effect compared to the shampoo in
which known ZPT is incorporated as the
dandruff-preventing agent. It is also obvious that the
sodium ascorbic acid tocopherol phosphate-incorporated
hair tonic has a remarkable dandruff-preventing effect,
compared with the diester-free hair tonic.
Experimental Example 2
The loss of hair-preventing effect was ex~mined by
changing the amount of the potassium ascorbic acid
~-tocopherol phosphate incorporated in the hair tonic,
and six kinds of hair tonics having a composition shown
in Table 2 were prepared. Thirty men 25 to 55 years old
were selected at random as the subjects, and 5 subjects
were alloted to each sample hair tonic. The hair tonic
- 1 336688
_ 18 -
was used once a day, and the number of hairs lost over 2
days after washing, during the control period (the
above-mentioned phosphoric acid diester-free hair tonic
was used), was compared with the number of hairs lost
for 2 days after washing during the experimental period.
When the reduction ratio of the loss of hair was higher
than 10%, it was judged that a loss of hair-preventing
effect was obtained, and when the ratio of the fallen
hairs was lower than 10%, it was judged that the loss of
hair-preventing effect was not obtained. The results
are shown in Table 2.
Table 2
Sample No.
1 2 3 4 5 6
Composition phosphoric 0.0010.01 0.05 0.1 210
of Hair acid diester
Tonic (X) obtained
in Example 2
ethanol (~) ~ 75%
purified water in amount such that total
quantity was lOOZ
Dandruff- effective 1 3 4 5 5 5
Preventing (number of
Effect subjects)
not effective 4 2 1 0 0 0
(number of
subjects)
In the case of the hair tonic comprising 0.001% by
weight of the phosphoric acid diester of the present
invention (sample No. 1), the loss of hair-preventing
effect was observed in one subject among five subjects.
In the case of sample No. 2 where the amount of the
phosphoric acid diester was increased 10 times, a
19 - 1 336688
remarkable effect was observed in 3 subjects among 5
subjects. A remarkable loss of hair effect was observed
in all 5 subjects when the potassium ascorbic acid
tocopherol was incorporated in an amount of at least
0.1% by weight (sample No. 4).
Experimental Example 3
The anti-oxidizing action of the diester of
phosphoric acid with ascorbic acid and tocopherol
according to the present invention will now be0 described.
A screw tube having a capacity of 50 ml was charged
with 1 g of ethyl linoleate, and 0.2 mg of a sample
substance shown in Table 3 was added and mixed with the
ethyl linoleate. The mixture was then irradiated with
ultraviolet rays for 3 hours to effect air oxidation,
and the amount of the ethyl linoleate peroxide formed
was measured by high-speed liquid chromatography (HPLC).
The amount of the peroxide shown in Table 3 is a
relative value calculated on the assumption that the
value obtained when the sample substance was not added
(control) was 100%.
Table 3
Amount (Z) of
Sample Substance . .
Llpld Peroxlde
Control 100
~-tocopherol/vitamin A acid ester 71.9
vitamin E/nicotinic acid ester 72.5
tocopherol 72.7
potassium ascorbic acid ~-toco- 51.2
pherol phosphate
According to the results of research by the present
- 1 336688 - 20 -
inventors, it was found that a very close relationship
is established between a formation of dandruff and the
amount of lipid peroxide in dandruff. Namely, it was
found that if the amount of the lipid peroxide in the
head skin is reduced, the formation of dandruff can be
controlled, and accordingly, an antioxidant capable of
reducing the quantity of a lipid peroxide is inherently
effective as a dandruff-control agent.
As apparent from the results shown in Table 3, the
compound of the present invention has a much higher
antioxidizing function than the conventional tocopherol
esters.
Example 1
To 60 g of ethyl alcohol, 2 g of polyoxyethylene
(40 moles) oleyl alcohol and an appropriate amount of a
perfume were added, and a solution was formed at room
temperature to obtain an alcohol phase. Separately, 5 g
of glycerol and 0.1 g of potassium ascorbic acid
r~-tocopherol phosphate were added to 32.9 g of purified
water, and the mixture was heated to form a solution,
the solution was cooled, and an appropriate amount of
Yellow 1 was added to the solution. The alcohol phase
was then added to the aqueous phase to effect
solubilization and obtain a hair tonic having a
dandruff-preventing effect and a loss of hair-preventing
effect.
Example 2
To 50.0 g of ethyl alcohol, 20 g of
polyoxypropylene butyl ether and an appropriate amount
of a perfume were added and a solution was formed at
room temperature. Then, 0.2 g of magnesium ascorbic
acid ~-tocopherol phosphate was added to 29.8 g of
purified water and the mixture was heated to form a
solution. After cooling, an appropriate amount of
Blue 2 was added to the solution, and this solution was
mixed with the above-mentioned alcohol phase to obtain a
hair liquid having a dandruff-preventing effect and a
- 21 _ l 3 3 6 688
loss of hair-preventing effect.
Example 3
An oil phase was prepared by heating at 80C a
mixture comprising 2 g of stearic acid, 1.5 g of cetyl
alcohol, 3 g of vaseline, 13 g of liquid paraffin, 1 g
of polyoxyethylene (10 moles) mono-oleate, and an
appropriate amount of a perfume. Separately, an aqueous
phase was prepared by heating at 80C a mixture
comprising 5 g of propylene glycol, 1 g of
triethanolamine, 0.05 g of sodium ascorbic acid
~-tocopherol phosphate, and 73.45 g of purified water.
The oil phase was gradually added to this aqueous phase
while stirring, to effect emulsification, and the
emulsion was cooled to obtain a head skin milky lotion
having a dandruff-preventing effect and a loss of
hair-preventing effect.
Example 4
An oil phase was prepared by heating at 80C a
mixture comprising 2 g of stearic acid, 7 g of stearyl
alcohol, 2 g of lanoline, 5 g of squalane, 6 g of octyl
dodecanol, 3 g of polyoxyethylene (10 moles) cetyl
ether, 2 g of glyceryl monostearate, and an appropriate
amount of a perfume. Separately, an aqueous phase was
prepared by heating at 80C a mixture comprising 5 g of
propylene glycol, 2 g of sodium ascorbic acid
~-tocopherol phosphate, and 66.0 g of purified water.
The oil phase was gradually added to the aqueous phase
while stirring, to effect emulsification, and the
emulsion was cooled to obtain a hair cream having a
dandruff-preventing effect and a loss of hair preventing
effect.
Example 5
To 70.0 g of purified water were added 15 g of
triethanolamine lauryl sulfate, S g of coconut oil fatty
acid monoethanolamide, 10.0 g of calcium ascorbic acid
~-tocopherol phosphate, and appropriate amounts of
Red 2, Red 22 and a perfume, and the mixture was heated
- 22 - 1 3 3 6 6 8 8
and was then cooled to obtain a hair shampoo having a
dandruff-preventing effect and a loss of hair-preventing
effect.
Example 6
5 In 74.49 g of purified water 3.5 g of polyethylene
glycol 1500, 1 g of triethanolamine and 0.01 g of
potassium ascorbic acid ~-tocopherol phosphate were
dissolved under heating, and the solution was maintained
at 70C. Then, 2.5 g of stearic acid, 1.5 g of cetyl
alcohol, 5 g of vaseline, 10 g of squalane, and 2 g of
polyoxyethylene (10 moles) mono-oleate were heated,
dissolved, maintained at 70C and added to the
above-mentioned aqueous phase. After preliminary
emulsification, the mixture was uniformly emulsified by
a homomixer and gradually cooled to obtain a hair lotion
having a dandruff-preventing effect and a loss of
hair-preventing effect.
