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Description  |
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BACKGROUND OF THE INVENTION
1. Field of the Invention:
The present invention relates to a novel phosphate, a liposome comprising
the phosphate as a membrane costitutent, and a cosmetic or a liposome
preparation comprising the liposome.
2. Description of the Background Art:
Liposomes consisting of spheres of single- or multi lipid bilayers are
drawing a great deal of attention as carriers of various medicines.
Liposomes comprising an active component are used as cosmetic ingredients.
In order to promote penetration into the hair and the skin, to increase
the effect of active components encapsulated in liposomes, and to ensure a
prolonged effect, liposomes incorporated into cosmetic composition must be
small-sized vesicles which are stable over a long period of time. Natural
phospholipids, cholesterols, and the like are known as liposome producing
agents. A simple addition of these liposome producing agents to water will
result in multilamella large liposomes having a vesicle size of about 1-5
.mu.m. These liposomes have problems such as difficulty in penetration
through the skin and the like. Conventionally known methods of producing
liposomes are a method of using ultrasonic radiation, a method of removing
a surface-active agent from a mixed system of the surface-active agent and
a liposome, a method of charging an ethanol solution of a
liposome-producing agent into water, the reverse micelle method, and the
like [e.g. L. S. Rao, Liposome Technology, edited by G. Gregoriadis, CRC
Press, USA (1984)].
These methods, however, have problems such as the incapability of a
large-scale production, difficulty of producing a high concentration
liposome, and the like. Besides, small unilamella vesicles produced by
these methods tend to become large multilamella vesicles with the passage
of time.
As a means of resolving such problems, for example, a method of producing a
small liposome having a 30 nm radius by simply charging a
didodecyldimethylammonium cation having a hydroxyl ion or an acetate ion
as a counter ion into water has been proposed [Ninham, Evans, et al.,
Faraday Discuss. Chem. Soc., 81, (1986)].
This method, however, also has problems such as an extremely narrow
concentration range capable of producing small size liposomes, which makes
it difficult to incorporate the liposomes into cosmetic composition
containing many compounds, strictly limited conditions under which an
active component is encapsulated in liposomes, the use of a cationic
surface-active agent as a liposome-producing agent which is undesirable to
incorporate into cosmetic compositions in a large amount, and the like.
In this situation, development of small-sized, stable liposomes which are
capable of encapsulating active components therein and which can easily be
produced in a large scale has been desired. There has also been a strong
desire for the development of cosmetic compositions which can exhibit
their effects for a long period of time while imparting only low
irritation to living bodies.
As a result of extensive studies, the present inventors found that novel
diphosphate represented by the formula (II) shown below could be prepared
at a high yield from readily available raw materials by a simple reaction
and procedure. The inventors further found that the diphosphate of formula
(II) and a monophosphate of the formula (I) also shown below could be
produced at a large, industrial scale, that these phosphates could
independently or together form small and stable liposomes which can
include active components therein, and further that cosmetic compositions
comprising these phosphates penetrate well into the hair and the skin, and
exhibit long-lasting excellent moisture-retaining, beauty, skin-activation
effects. In addition, the inventors discovered a liposome preparation
comprising a liposome which includes active components therein. Such
findings have led to the completion of the present invention.
SUMMARY OF THE INVENTION
Accordingly, an object of the present invention is to provide a liposome
comprising as its membrane constituents a monophosphate represented by the
formula (I), a diphosphate represented by the formula (II), or both,
##STR1##
wherein A represents the following group (i), (ii), or a mixture thereof:
##STR2##
wherein R.sup.1 and R.sup.2 may be the same or different and individually
represent a group --OCOR.sup.3, --OR.sup.4, or a mixture thereof wherein
R.sup.3 and R.sup.4 may be the same or different and individually
represent an alkyl or alkenyl group having 6-32 carbon atoms, or R.sup.1
and R.sup.2 may together form the group, wherein n is an integer of
11-19; M represents a hydrogen atom, an alkali metal, an alkaline earth
metal, an ammonium, alkylammonium, or alkanolammonium group; and Z
represents a residue of either one of the following groups (1)-(5) from
which one primary hydroxyl group is removed,
(1) a mono- or polyether group represented by the formula
HO--(Y--O--).sub.m --H, wherein m is an integer of 2-50, and Y represents
an alkylene or substituted alkylene group having 2-4 carbon atoms,
(2) a polyglycerol group having a condensation degree of 2-50,
(3) a monosaccharide having 5-7 carbon atoms and at least two primary
hydroxyl groups or a disaccharide which is composed of the monosaccharide
units,
(4) a sugar alcohol having 4-7 carbon atoms, or
(5) a monosaccharide having 5-7 carbon atoms and one primary hydroxyl
group, which may be substituted by an amino or acetyl amino group, a
disaccharide which is composed of the monosaccharide units, or a glycoside
derived from the monosaccharide or disaccharide;
##STR3##
wherein A and M have the same meaning as defined in formula (I), and X
represents a residue of either one of the following groups (1)-(3) from
which two primary hydroxyl groups are removed,
(1) a mono- or polyether group represented by the formula
HO--(Y--O--).sub.m --H, wherein m is an integer of 2-50 and Y represents
an alkylene or substituted alkylene group having 2-4 carbon atoms,
(2) a polyglycerol group having a condensation degree of 2-50,
(3) a monosaccharide having 5-7 carbon atoms and at least two primary
hydroxyl groups or a disaccharide which can be decomposed into such a
monosaccharide.
Another object of the present invention is to provide a cosmetic
composition comprising a monophosphate of the above formula (I) or a
diphosphate of the above formula (II), or both.
Still another object of the present invention is to provide a diphosphate
of the above formula (II).
Other objects, features and advantages of the invention will hereinafter
become more readily apparent from the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a drawing showing an NMR spectrum of diphosphatidyl PEG400
prepared in Example 1 and
FIG. 2 is a drawing showing an IR spectrum of the same compound.
DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
The group A of formula (I) or (II) may be either the above-mentioned group
(i) or (ii). Also, the mono-or diphosphate of formula (I) or (II) may be a
mixture of the phosphates having a different group A selected from (i) and
(ii). Alkyl or alkenyl groups represented by R.sup.3 and R.sup.4 may be
such groups as hexyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl,
octadecyl, eicosyl, docosyl, tetracosyl, hexacosyl, octacosyl, triacontyl,
dotriacontyl, 2-ethylhexyl, octadienyl, decadienyl, dodecadienyl,
tetradecadienyl, hexadecadienyl, octadecadienyl, eicosadienyl,
docosadienyl, tetracosadienyl, hexacosadienyl, octacosadienyl,
triacontadienyl, dotriacontadienyl, hexadecatrienyl, octadecatrienyl,
eicosatrienyl, docosatrienyl, tetracosatrienyl, hexacosatrienyl,
octacosatrienyl, triacontatrienyl, dotriacontatrienyl, eicosatetraenyl,
docosatetraenyl, tetracosatetraenyl, hexacosatetraenyl, octacosatetraenyl,
triacontatetraenyl, dotriacontatetraenyl, docosapentaniel,
tetracosapentaniel, hexacosapentaniel, octacosapentaniel,
triacontapentaniel, dotriacontapentaniel, docosahexaniel,
tetracosahexaniel, hexacosahexaniel, octacosahexaniel, triacontahexaniel,
dotriacontahexaniel, or the like.
As specific examples of the group represented by M of formulae (I) and
(II), which generically represents a hydrogen atom, an alkali metal, an
alkaline earth metal, an ammonium, alkylammonium, or alkanolammonium
group, given, beside hydrogen and ammonium, are potassium, lithium,
sodium, beryllium, magnesium, calcium, strontium, barium,
triethanolammonium, trimethylammonium, triethylammonium, and the like.
Examples of alkylene groups represented by Y in the mono- or polyether
group of formula HO--(--Y--O--).sub.m --H described in item (1) include
such groups as ethylene, propylene butylene, 1-methylpropylene, and the
like. Among the integer m which is generically 2-50, an integer of 4-50is
preferable, with the range 4-20 being particularly preferable. Specific
examples of polyethers are polyethylene glycol having an average molecular
weight of 400 (hereinafter referred to as PEG400), polyethylene glycol
having an average molecular weight of 600 (hereinafter referred to as
PEG600), polypropylene glycol having an average molecular weight of 200
(hereinafter referred to as PEG200), and the like.
Among the condensation degree of 2-50 of the polyglycerol group described
in item (2), a range of 4-50 is preferable, with the particularly
preferable range being 4-20. Specific examples of polyglycerols include
polyglycerol having an average molecular weight of 500 (hereinafter
referred to as PG500), polyglycerol having an average molecular weight of
750 hereinafter referred to as PG750), and the like.
Given as examples of monosaccharides described in item (3) having 5-7
carbon atoms and at least two primary hydroxyl groups are xylulose,
ribulose, sorbose, psicose, tagatose, sedoheptulose, glucoheptulose,
mannoheptulose, and the like, and of examples of the disaccharides
composed of such monosaccharide units are sucrose, maltose, cellobiose,
trehalose, lactose, and the like.
Examples of sugar alcohols described in item (4) include erythritol,
ribitol, arabitol, xylitol, sorbitol, mannitol, galactitol, sedoheptitol,
perseitol, and the like.
Examples of saccharides and glycosides described in item (5);
monosaccharides having 5-7 carbon atoms and one primary hydroxyl group,
which may be substituted by an amino or acetyl amino group, disaccharides
which are composed of the monosaccharide units, or a glycoside derived
from the monosaccharide or disaccharide; include arabinose, ribose,
2-deoxyribose, lyxose, xylose, .alpha.- or .beta.-methylxyloside,
2-O-methylxylose, .beta.-methylarabinoside, 2-deoxyglucose, glucose,
galactose, mannose, talose, melibiose, gentiobiose, .alpha.- or
.beta.-methylgalactoside, .alpha.- or .beta.-methylglucoside, .alpha.- or
.beta.-methylmannoside, 3-O-methylglucose, 1-thio-.beta.-galactose,
.beta.-thioglucose, 5-thioglucose, methyl-.beta.-thiogalactoside,
ethyl-.beta.-thioglucoside, 2-deoxygalactose, .alpha.-chloralose,
.alpha.-glucoheptose, galactosamine, glucosamine, mannosamine,
N-acetylgalactosamine, N-acetylglucosamine, N-acetylmannosamine,
methyl-3-amino-3-deoxy-.beta.-glucoside,
methyl-3-amino-3-deoxy-.beta.-mannoside, streptozotocin, salicin, arbutin,
1-O-phenyl-.alpha.- or .beta.-glucoside, 1-O-phenyl-.alpha.- or
.beta.galactoside, o-nitrophenyl-.alpha.- or .beta.-galactoside,
m-nitrophenyl-.alpha.- or .beta.-galactoside, p-nitrophenyl-.alpha.- or
.beta.-galactoside, p-nitrophenyl-.alpha.- or .beta.-glucoside,
o-nitrophenyl-.alpha.- or .beta.-glucoside, p-nitrophenyl-.alpha.- or
.beta.-mannoside, p-nitrophenyl-1-thio-.beta.-galactoside,
o-nitrophenyl-1-thio-.beta.-galactoside,
p-nitrophenyl-1-thio-.beta.-glucoside, o-nitrophenyl-.beta.-xyloside,
p-nitrophenyl-.alpha.- or .beta.-xyloside, phenyl-.alpha.- or
.beta.-thiogalactoside, mandelonitrileglucoside, and the like.
Among the phosphates of the present invention, preferable phosphates are
those in which A in formula (I) or (II) is the formula (i) group and in
which R.sup.1 and R.sup.2 are a combination of groups selected from
lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, lynoleoyl, lynolenoyl,
arachidonoyl, docosahexanoyl, eicosapentanoyl, and the like. Another
preferable phosphates are those in which A in formula (I) or (II) is a
mixture of groups having the same distribution with those of natural
phospholipids derived from egg yolk, soy bean, or the like. They are, for
example, mono- or diphosphatidyl PEG400, mono- or diphosphatidyl PEG600,
mono- or diphosphatidyl PPG200, mono- or diphosphatidyl PG500, mono- or
diphosphatidyl PG750, or their mixtures.
A phosphate used in the present invention can be prepared according, for
example, to the following reaction scheme.
##STR4##
wherein A and M have the same meanings as defined above and B represents a
residue of an organic base having not more than 4 carbon atoms and a
primary hydroxyl group and from which a hydroxyl group is removed.
According to the above reaction formula, a phosphate of formula (I), (II),
or a mixture thereof is prepared by a phosphatidyl transfer reaction,
desirably in a solvent, of a natural or synthetic phospholipid (III) and
an alcohol of (1)-(5) in the presence of phospholipase D.
A phospholipid (III) and an alcohol of (1)-(5) can be selected depending on
the target phosphate. There are no specific limitations as to their types.
Given as examples of phospholipids (III) are egg yolk lecithin, soy bean
lecithin, synthetic lecithins, and the like, and as examples of alcohols
are PEG400, PEG600, PPG200, PG500, PG750, fructose, and the like.
Also, there are no specific limitations as to the source from which a
phospholipase D which is used in the reaction is derived. For example,
phospholipase DM derived from a microorganism belonging to the genus such
as Nocardiopsis sp. No. 779 (FERM-P No. 6133; the international deposit
number BP 512 under the Budapest Treaty) or phospholipase DM derived from
a microorganism belonging to the genus such as Actinomadura sp. No. 362
(FERM-P No. 6132; the international deposit number BP 511 under the
Budapest Treaty).
A typical example of a solvent which can be used in the reaction is a mixed
solvent of an organic solvent such as ether, ethyl acetate, benzene,
chloroform, or the like and a suitable aqueous solvent. A suitable
additive which may promote the activity of phospholipase D or which can
help to stabilize the enzyme can be added to the aqueous solvent. Such
suitable additives include proteins such as albumin, casein, and the like,
buffer agents such as acetic acid, citric acid, phosphoric acid, and the
like, neutral salts such as calcium chloride and the like.
A molar ratio of the compounds to be reacted and amounts of phospholipase D
and the solvent may be determined from among suitable ranges. Generally, a
suitable range of the molar ratio of a phospholipid (III) and a polyhydric
alcohol of (1)-(5) is for one mole of a phospholipid (III) 0.1-100 moles
of a polyhydric alcohol. An amount of a phospholipase D to be used is
about 10-100,000 units, preferably 100-1,000 units, per 1 g of
phospholipid (III). An amount of a solvent which may be used is about
2-100 times by weight of the phospholipid (III). The reaction temperature
and the reaction time can be suitably determined. Preferable range is
about 20.degree.-60.degree. C. and 1-72 hours.
In the above reaction, a phosphatidyl group transfer is effected on the
primary --OH group of an alcohol of (1)-(5) by phospholipase D.
Accordingly, phosphates of the present invention are usually obtained as a
mixture of monophosphates of formula (I) and diphosphates of formula (II).
In the present invention, such a phosphate mixture can be used as is, or as
mono- or diphosphates after their separation from the mixture. When used
as a mixture, a preferable ratio of the monophosphates of formula (I) and
the diphosphates of formula (II) in the mixture is in the range of
1:99-99:1 by weight. Separation of phosphates from the mixture can be
performed by means of solvent fractionation using an organic solvent such
as acetone, methanol, ethanol, isopropanol, or the like, separating liquid
method, silica gel chromatography, high performance liquid chromatography,
and the like.
Monophosphates of formula (I) and diphosphates of formula (II) thus
prepared can produce stable, small size liposomes. It is desirable in the
preparation of such small-size liposomes to incorporate a water-soluble
salt and/or a surface-active agent [hereinafter collectively referred to
as "components (b)"]into the monophosphates of formula (I) and/or
diphosphates of formula (II) [these are hereinafter collectively referred
to as "phosphates (a)"].
Organic or inorganic salts having a solubility in water of 10.sup.-4 M or
greater at room temperature are preferable as a water-soluble salt. Such
inorganic salts include salts of hydrochloric acid, nitric acid, sulfuric
acid, phosphoric acid, carbonic acid, hydrobromic acid, hydroiodic acid,
or the like having an alkali metal, ammonium, or the like as a counter
ion. Specific examples of preferable inorganic salts are potassium
bromide, potassium chloride, potassium dihydrogenphosphate, dipotassium
hydrogenphosphate, potassium sulfate, potassium iodide, potassium nitrate,
lithium bromide, lithium chloride, lithium iodide, lithium nitrate,
lithium sulfate, ammonium bromide, ammonium chloride, ammonium carbonate,
ammonium hydrogencarbonate, ammonium dihydrogenphosphate, diammonium
hydrogenphosphate, ammonium iodide, ammonium nitrate, ammonium sulfate,
sodium bromide, sodium carbonate, sodium chloride, sodium
hydrogencarbonate, sodium dihydrogenphosphate, disodium hydrogenphosphate,
sodium nitrate, sodium phosphate, sodium sulfate, and the like. Organic
salts which can be used include alkanolamine chloride, sulfate, phosphate,
and the like, and salts of benzoic acid, acetic acid, salicylic acid,
oxalic acid phthalic acid, gluconic acid, 1-naphthalenesulfonic acid,
2-naphthalenesulfonic acid, tartaric acid, maleic acid, malonic acid,
succinic acid, fumaric acid, propionic acid, ascorbic acid, mandelic acid,
malic acid, citric acid, or the like having an alkali metal or ammonium
ion as a counter ion. Specific examples of preferable organic salts are
triethanolammonium chloride, triethanolammonium dihydrogenphosphate,
triethanolammonium sulfate, sodium benzoate, potassium benzoate, ammonium
benzoate, sodium acetate, potassium acetate, ammonium acetate, sodium
salicylate, potassium salicylate, ammonium salicylate, sodium oxalate,
potassium oxalate, ammonium oxalate, sodium phthalate, potassium
phthalate, ammonium phthalate, sodium gluconate, potassium gluconate,
ammonium gluconate, ammonium 1-naphthalenesulfonate, potassium
2-naphthalenesulfonate, ammonium 2-naphthalenesulfonate, sodium
2-naphthalenesulfonate, potassium tartarate, sodium maleate, potassium
maleate, sodium malonate, sodium succinate, sodium fumarate, sodium
propionate, triethanolammonium propionate, sodium ascorbate,
triethanolammonium ascorbate, potassium ascorbate, sodium mandelate,
sodium malate, sodium citrate, potassium citrate, triethanolammonium
citrate, and the like. Among these, particularly preferable salts are
sodium chloride, sodium sulfate, sodium hydrogencarbonate, ammonium
chloride, ammonium sulfate, sodium acetate, and the like.
In order to prepare the liposome of the present invention it is desirable
to use the water-soluble salt of the component (b) and the phosphate (a)
at a (a)/(b) ratio of 10.sup.-3 -10.sup.3, and preferably of 0.1-10. Also,
it is desirable that the water-soluble salt be used at an ionic strength
in water of about 10.sup."4 -1 M, preferably 10.sup.-3 -0.1 M.
Surface active agents used as the component (b) may be of anionic,
cationic, nonionic, or amphoteric. There are no limitations as to their
types and amounts. A range of the surface-active agent to be used as the
component (b) for the phosphates (a), the phosphate, in molar ratio
(a)/(b), is 10.sup.-3 -10.sup.3, with a preferable range being about
0.5-100, and the most preferable range being about 1-10.
Given as examples of anionic surface-active agents used as a component (b)
in this invention are alkyl sulfates, alkyl benzene sulfonates, stearates,
palmitates, myristates, oleates, hexadecadienates, hexadecatrienates,
hexadecatetraenates, octedecadienates such as linoleates,
octedecatrienates such as linolenates, eicosatetraenates such as
arachidates, eicosapentaenates, docosahexaenates, alkylphosphates,
polyoxyethylenealkylether phosphates, polyoxyethylenealkylether sulfates,
dialkylphosphates, and the like. Specific examples of preferred
surface-active agents are sodium dicetylphosphate, triethanolammonium
dicetylphosphate, sodium 2-decyltetradecylphosphate, and the like.
Cationic surface-active agents which can be used include, for example,
monoalkyltrimethylammonium salts or dialkyldimethylammonium salts. As
specific examples of such surface-active agents, cetyltrimethylammonium
bromide, distearyldimethylammonium chloride, and the like are given.
Examples of nonionic surface-active agents include
polyoxyethylenealkylether, polyoxyethylenealkylphenylether,
glycerolalkylether, sorbitan fatty acid ester, polyoxyethylene sorbitan
fatty acid ester, polyoxyethylene sorbitol fatty acid ester, glycerol
fatty acid ester, polyglycerol fatty acid ester, polyoxyethylene fatty
acid ester, propylene glycol fatty acid ester, polyoxyethylenealkylamine,
fatty acid esters of fructose and glucose, and the like. Among these,
specific examples of nonionic surface-active agents are preferably used
are 9-methylheptadecylglycerylether, sorbitan monostearate, glycerol
oleate, sucrose fatty acid esters, and the like. Highly hydrophobic
compounds such as cholesterols can be included in the nonionic
surface-active agents used in the present invention.
As examples of amphoteric surface-active agents, alkyl betaines, sulfo
betaines, natural or synthetic phosphatidyl choline and phosphatidyl
ethanolamine, and the like are given. Preferable compounds among these are
steraryl phosphobetaine, dipalmitoyl phosphatidyl choline, and the like.
An amount of water into which the components (b), the water-soluble salt
and/or the surface-active agent, are dispersed is 10-10.sup.4, preferably
20-103, times by weight of the phosphate, the phosphates (a).
In order to produce small liposomes of the present invention, the
components (a) and (b) are added to a suitable amount of water and the
mixture is gently stirred. The production of liposomes can be performed at
room temperature. A temperature of 40.degree.-80.degree. C. is, however,
generally more efficient. There are no restrictions as to the manner by
which the components (a) and (b) are added to water. For instance, it is
possible to blend components (a) and (b) in advance or first to disperse
component (b) in water followed by the addition of component (a).
Although liposomes prepared by conventional methods normally have an
average diameter of 1-5 .mu.m, it is possible to prepare liposomes having
much smaller diameter, e.g. an average diameter smaller than 500 nm.
Various cosmetically acceptable active components can be incorporated into
liposomes of the present invention. They may be either hydrophillic
compounds, hydrophobic compounds, or mixtures of these.
Given as examples of such active components are vitamins and their
derivatives such as vitamin A, vitamin B.sub.1, vitamin B.sub.2, vitamin
B.sub.6, vitamin B.sub.12, vitamin C, vitamin D, vitamin H, vitamin K,
vitamin M, vitamin Q, pantothenyl alcohol, calcium pantothenate, benzyl
nicotinate, hesperidin, hesperetin, and the like; polyols and their
derivatives such as glycerol, nitroglycerol, diglycerides, triglycerides,
and the like; sugars and their derivatives such as glucose fructose,
sorbitol, galactose, mannose, inositol, maltitol, maltose, lactose,
sucrose, trehalose, cellobiose, adenylthiomethylpentose, and the like;
polysaccharides and their derivatives such as hyaluronic acid, chondroitin
sulfuric acid, and the like; sugar phosphates and salts thereof as well as
their derivatives such as glucose-1-phosphate, glucose-6-phosphate,
mannose-6-phosphate, galactose-6-phosphate, fructose-6-phosphate,
glucose-1,6-diphosphate, fructose-1,6-diphosphate,
fructose-2,6-diphosphate, and their sodium or potassium salts, and the
like; amino acid and their derivatives such as alanine, leucine, lysine,
asparagine, aspartic acid, cysteine, proline, glutamine, serine, glutamic
acid, glycine, histidine, tyrosine, isoleucine, valine, and the like;
cholesterols and their derivatives, ceramides and their derivatives,
highly unsaturated fatty acids and their derivatives such as linoleic
acid, linolenic acid, arachidonic acid, docosahexanenic acid,
prostaglandin, prostacyclin, leukotriene, and the like;
pyrrolidonecarboxylic acid, glycyrrhizin, bisabolol, benzalconium
chloride, benzethonium chloride, paraben ester, menthol, resorcinol,
hinokitiol, squalene, anthranilic acid, urea, adrenocortical hormone,
estrogen, follicle-stimulating hormone, androgen, thyroxine, pituitary
hormone, posterior pituitary extracts, thymic hormone, placental
gonadotropin, epsilon-aminocaproic acid, allantoin, halocarbane, camphor,
hydroxyammonium chloride, glutathion and its derivative,
methyl-2,5-diisopropyl cinnamate, p-aminobenzoic acid ester, zinc
bis(2-pyridylthiol-1-oxide), aminophenol type anti-hystamines, estradiol,
ethylestradiol, salicylic acid and its derivatives, chlorodiphenhydramine,
isopropylmethylphenol, chlorohexidine chloride, allantoin chlorohydroxy
aluminum, homosulfamine, scopolamine, clonidine, isosorbide sulfate,
5-fluorouracil, capronium chloride, acetylcholine, and antibiotics such as
penicillin, cephalosporine, streptomycin, chloromycin, and the like.
Although there are no restrictions as to the amount of the active
components to be incorporated into the liposome of the present invention,
it is desirable to use them in an amount of about 10.sup.-6 -30% by weight
based on the amount of water used in preparing the liposome.
Active components can be added by mixing them with the mixture of
components (a) and (b) or by adding a solution of the active components
when the liposome is prepared. Another method is to mix the active
components with a brine or a dispersion of a surface-active agent and to
use such a brine or dispersion in the liposome preparation.
Incorporation of phosphates (a) is important for obtaining a cosmetic
composition having a superior permeability into the skin and hair and
exhibiting long-lasting moisturizing, beauty, and skin-activation effects.
Although there are no restrictions as to the amount of phosphates (a) to be
incorporated into the cosmetic of the present invention, it is desirable
to use them in an amount of 0.01-50% by weight, particularly 0.1-40% by
weight, based on the total weight of the cosmetic composition. A
large-scale industrial production of low-concentration (about 0.01-10% by
weight) phosphates (a) is possible. Such low-concentration phosphates can
produce small-size liposomes which can contain active components therein.
Cosmetics comprising such a liposome have a semi-transparent appearance.
In contrast, higher concentration (about 10-50% by weight) phosphates
produces a lamella phase and cosmetics comprising such phosphates exhibit
a transparent gel-like appearance. This type of phosphates can produce a
stable emulsion cosmetic composition by adding an oil or fat component.
The transparent gel-like cosmetic composition can be prepared by mixing the
phosphates (a), water, and other components. When the liposome comprising
the phosphate (a) of the present invention is to be formed in a cosmetic
composition, components (b), i.e. the water-soluble base, the
surface-active agent, or both, must be included. The liposome-containing
cosmetic composition can be prepared according to the above-mentioned
method for the preparation of the liposomes. Various active components can
be added to the cosmetic composition. These active components may be
present in the cosmetic composition as they are incorporated in the
liposomes. The following compounds are given as examples of such active
components. Vitamins and their derivatives such as vitamin A, vitamin B' | | |
