Link: Pharm/Biotech Resources
Title: O/W emulsion composition and method of preparing
the same
United States Patent: 6,946,436
Issued: September 20, 2005
Inventors: Wakamatsu; Kosaburo (Kyoto, JP); Tanaka; Masahiko (Otsu, JP); Yoshino; Noboru (Kyoto, JP)
Assignee: Otsuka Pharmaceutical Co., Ltd. (Tokyo, JP)
Appl. No.: 432400
Filed: November 22, 2001
PCT Filed: November 22, 2001
PCT NO: PCT/JP01/10230
371 Date: May 21, 2003
102(e) Date: May 21, 2003
PCT PUB.NO.: WO02/41853
PCT PUB. Date: May 30, 2002
Abstract
The present invention provides an O/W emulsion composition containing an electrolyte. More particularly, the invention provides an O/W emulsion composition excellent in emulsion stability despite its electrolyte content. The O/W emulsion composition of the invention can be prepared using an electrolyte, a polyglycerin fatty acid ester, an alkanoyl lactylic acid or the salt thereof, an acrylic acid-alkyl methacrylate copolymer, water, an oil, and preferably a polyhydric alcohol.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide an O/W emulsion
composition that is excellent in emulsion stability despite having an
electrolyte contained as an ingredient and that stably maintains its
emulsified state over a long period of time. Another object of the
invention is to provide various external preparations that exhibit, in
addition to good emulsion stability, desired functions derived from the
electrolyte contained as an ingredient therein, and that can be used in
the field of medical or quasi-medical drugs and in the field of fragrances
and cosmetics.
Still another object of the invention is to provide a method for preparing
an O/W emulsion composition excellent in emulsion stability despite its
electrolyte content, and a method for stabilizing the emulsion of the O/W
emulsion composition containing an electrolyte.
The inventors conducted research for the purpose of stably emulsifying a
composition containing an electrolyte and found that it is possible to
emulsify electrolytes by the combined use of an acrylic acid-alkyl
methacrylate copolymer and a known emulsifier, i.e., a polyglycerin fatty
acid ester, even though the polyglycerin fatty acid ester alone could not
heretofore emulsify. However, the inventors also found that the emulsion
particles of the polyglycerin fatty acid ester and those of the acrylic
acid-alkyl methacrylate copolymer agglomerate due to long term storage or
temperature change, and they gelate on the inner wall of a container and
in the upper layer of the emulsion. The inventors conducted further
research in view of the above findings and discovered that the further
addition of an alkanoyl lactylic acid or the salt thereof prevents the
gelation caused by temperature change and disadvantages such as oil
floating and separation caused by long-term storage, thus enabling an
emulsion composition excellent in emulsion stability to be prepared. The
present invention has been accomplished based on these findings.
Specifically, the present invention provides the O/W emulsion compositions
described in the following Items 1 to 21:
Further, the present invention provides the methods for preparing an O/W emulsion composition as defined in Items 22 to 24 below:
 | 1) preparing a nonaqueous emulsion using a compound comprising a polyglycerin fatty acid ester, an alkanoyl lactylic acid or the salt thereof, an oil, and, as required, a polyhydric alcohol; |
| 2) preparing an aqueous solution using a composition comprising an electrolyte, water, and an acrylic acid-alkyl methacrylate copolymer; and |
| 3) blending the nonaqueous emulsion with the aqueous solution to give the emulsion composition. |
The methods described above include the following embodiments:
Moreover, the present invention provides methods for stabilizing the emulsion of the O/W emulsion composition as defined in the following Items 25 and 27:
Item 25. A method for stabilizing the emulsion of an O/W emulsion composition containing an electrolyte, water, and an oil, the method comprising incorporating a polyglycerin fatty acid ester, an alkanoyl lactylic acid or the salt thereof, an acrylic acid-alkyl methacrylate copolymer, and, as required, a polyhydric alcohol into the emulsion composition.
The methods described above for stabilizing the emulsion of an O/W emulsion composition include the following embodiments:
BEST MODE FOR CARRYING OUT THE INVENTION
(1) O/W Emulsion Composition and Method for Preparation thereof
The O/W emulsion composition of the present invention essentially contains
an electrolyte, water, a polyglycerin fatty (aliphatic) acid ester, an
alkanoyl lactylic acid or the salt thereof, an acrylic acid-alkyl
methacrylate copolymer, and an oil.
Electrolytes usable in the invention are not limited. Preferable are those
that exhibit physiological functions when applied to the skin. Examples
include a wide variety of electrolytes that can be incorporated into
external preparations, particularly cosmetics, and externally-applied
medical and quasi-medical drugs. Preferable are those that are water
soluble or hydrophilic. Specific examples of usable electrolytes are
adenine, adenosine monophosphate, adenosine diphosphate, adenosine
triphosphate, cyclic adenosine monophosphate, and like adenylic acid
derivatives, and the salts thereof; guanine, guanosine monophosphate,
guanosine diphosphate, guanosine triphosphate, and like guanylic acid
derivatives, and the salts thereof; xanthine, xanthylic acid, inosinic
acid, and the salts thereof, and like purine nucleic acid-related
substances; uracil, cytosine, thymine, and the derivatives thereof, and
like pyrimidine nucleic acid-related substances; deoxyribonucleic acid and
the salt thereof, ribonucleic acid and the salt thereof, nucleoside,
nucleotide, and like nucleic acid-related substances; vitamin B1, vitamin
B2, vitamin B6, vitamin B12, niacin, pantothenic acid, biotin, folic acid,
lipoic acid, inositol, ascorbic acid, and like water-soluble vitamins, and
the derivatives thereof; serine, glycin, asparagine, aspartic acid,
lysine, arginine, threonine, cysteine, glutamic acid, pyrrolidone
carboxylic acid, and like amino acids, and the derivatives thereof. These
electrolytes may be used alone or in combination of two or more species.
Examples of the variety of salts described above include sodium salt,
potassium salt, and like alkali metal salts; arginine, lysine, and like
basic amino acid salts; ammonium salt, triethanolamine salt, and the like.
Preferable electrolytes are nucleic acid-related substances, especially
purine nucleic acid-related substances. Among them, adenylic acid
derivatives and the salts thereof such as adenosine phosphate and the like
are known to exhibit, when applied to the skin, a moisturizing effect by
increasing the number of free amino acids in the horny cell layer, and, in
addition, function to stimulate the turn over thereby preventing drying
and aging of the skin and improving the condition of rough skin.
Therefore, they are electrolytes that can be suitably used in the present
invention.
Specific examples of adenosine phosphates and the salts thereof include
adenosine 3′,5′-cyclic monophosphate, adenosine monophosphate, adenosine
monophosphate monosodium, adenosine monophosphate disodium, adenosine
diphosphate, adenosine diphosphate monosodium, adenosine diphosphate
disodium, adenosine triphosphate, adenosine triphosphate monosodium,
adenosine triphosphate disodium, adenosine triphosphate trisodium, and the
like. Preferable among these are adenosine monophosphate and the salts
thereof (adenosine monophosphate monosodium and adenosine monophosphate
disodium).
The proportion of the electrolyte contained in the emulsion composition is
not limited insofar as each electrolyte can exhibit the desired effects.
Particularly, although it varies depending on the kind of electrolyte
used, it is in a range of at least 0.1 wt. %, preferably 0.5 to 7 wt. %,
more preferably 1 to 6 wt. % per 100 wt. % of the final emulsion
composition.
The O/W emulsion composition of the present invention contains water as an
essential ingredient. Distilled water, ion-exchanged water, sterilized
water, or electrolyte-containing water can be used as the water
ingredient. Examples of electrolyte-containing water include sea water,
hot-spring water, mineral water, and the like. The term "sea water" herein
refers to surface sea water, intermediate sea water, deep sea water, and
ultra deep sea water.
The proportion of the water contained in 100 wt. % of the final emulsion
composition is not limited. Usually, it is suitably selected from a range
of 50 to 90 wt. %. Preferably, it is selected from a range of 60 to 80 wt.
%.
Polyglycerin fatty acid esters usable in the present invention are not
limited. Examples include esters of a C12-36 fatty acid and a
polyglycerin having a polymerization degree of 6 or more, especially 6 to
10. Fatty acids that form esters with polyglycerins include saturated,
unsaturated, linear or branched fatty acids. Specific examples are capric
acid, lauric acid, isotridecanoic acid, myristic acid, palmitic acid,
palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic
acid, behenic acid, ricinoleic acid, and the like.
Specific examples of polyglycerin fatty acid esters are hexaglyceryl
monolaurate, hexaglyceryl monoisostearate, hexaglyceryl monomyristate,
hexaglyceryl dioleate, hexaglyceryl dimyristate, hexaglyceryl dipalmitate,
hexaglyceryl distearate, hexaglyceryl dibehenylate, hexaglyceryl
trilaurate, hexaglyceryl trimyristate, hexaglyceryl tripalmitate,
hexaglyceryl tristearate, hexaglyceryl tribehenylate, hexaglyceryl
tetralaurate, hexaglyceryl tetramyristate, hexaglyceryl tetrapalmitate,
hexaglyceryl tetrastearate, hexaglyceryl tetrabehenylate, hexaglyceryl
pentalaurate, hexaglyceryl pentamyristate, hexaglyceryl pentapalmitate,
hexaglyceryl pentastearate, hexaglyceryl pentabehenylate, decaglyceryl
monocaprate, decaglyceryl monolaurate, decaglyceryl monomyristate,
decaglyceryl monopalmitate, decaglyceryl monostearate, decaglyceryl
monooleate, decaglyceryl monolinoleate, decaglyceryl monoisostearate,
decaglyceryl dicaprate, decaglyceryl dilaurate, decaglyceryl dimyristate,
decaglyceryl dipalmitate, decaglyceryl distearate, decaglyceryl
diisostearate, decaglyceryl trilaurate, decaglyceryl trimyristate,
decaglyceryl tripalmitate, decaglyceryl tristearate, decaglyceryl
trioleate, decaglyceryl tribehenylate, decaglyceryl pentastearate,
decaglyceryl pentaoleate, decaglyceryl pentaisostearate, decaglyceryl
heptastearate, decaglyceryl decastearate, decaglyceryl decaoleate,
decaglyceryl decaisostearate, and the like. However, the polyglycerin
fatty acid esters are not limited thereto.
The polyglycerin fatty acid esters may be used alone or in combination of
two or more species. Polyglycerin fatty acid esters having an HLB value of
10 or more, especially 10 to 15, can be suitably used. It is preferable to
use the polyglycerin fatty acid ester in a proportion of 0.05 to 6 wt. %
per 100 wt. % of the final emulsion composition, more preferably in a
proportion of 0.1 to 5.5 wt. %.
Alkanoyl lactylic acids usable in the invention are not limited. Examples
include alkanoyl lactylic acids having an alkanoyl group with 8 or more
carbons, preferably alkanoyl lactylic acids having a C8-18
alkanoyl group. Specific examples include octanoyl lactylic acid, caproyl
lactylic acid, 2-ethyl hexanoyl lactylic acid, lauroyl lactylic acid,
myristoyl lactylic acid, palmitoyl lactylic acid, stearoyl lactylic acid,
isostearoyl lactylic acid, oleoyl lactylic acid, 12-hydroxystearoyl
lactylic acid, linoleyl lactylic acid, and hebenoyl lactylic acid.
Preferable are stearoyl lactylic acid and isostearoyl lactylic acid. The
alkanoyl lactylic acids can be used in the form of a salt. Examples of
such salts include sodium salts, potassium salts, and like alkali metal
salts; ammonium salts, triethanolamine salts, and the like. Preferred are
sodium salts, more specifically, sodium stearoyl lactylate and sodium
isostearoyl lactylate.
The alkanoyl lactylic acids and the salts thereof may be used alone or in
combination of two or more species. It is preferable to use the alkanoyl
lactylic acid or the salt thereof in a proportion of 0.01 to 1 wt. % in
100 wt. % of the final emulsion composition, more preferably in a
proportion of 0.1 to 0.5 wt. %.
The polyglycerin fatty acid esters and alkanoyl lactylic acids and the
salts thereof are used as an emulsifier for the nonaqueous emulsion
prepared in the production process of the emulsion composition of the
invention. The proportion for blending a polyglycerin fatty acid ester
with an alkanoyl lactylic acid or the salt thereof is desirably such that
the HLB value of the mixture be 10 or more, preferably 10 to 13. Specific
examples of the proportion for blending a polyglycerin fatty acid ester
with an alkanoyl lactylic acid or the salt thereof are weight ratios of
95:5 to 60:40, preferably 90:10 to 70:30.
Acrylic acid-alkyl methacrylate copolymers usable in the invention are not
limited. Examples usually include those having an alkyl chain with 5 to 40
carbons. Preferred are those having an alkyl chain with 10 to 30 carbons.
Although not limited thereto, such polymers are commercially available,
for example, from Goodrich Corporation under the trademarks of Carbopol
and Pemulen, such as Carbopol 1342, Pemulen TR-1, and Pemulen TR-2.
The acrylic acid-alkyl methacrylate copolymers may be used alone or in
combination of two or more species. It is preferable to use the acrylic
acid-alkyl methacrylate copolymer in a proportion of 0.01 to 0.8 wt. % per
100 wt. % of the final emulsion composition, more preferably in a
proportion of 0.3 to 0.6 wt. %, still more preferably in a proportion of
0.4 to 0.6 wt. %.
Oils usable in the invention are not limited. Specific examples include
peanut oil, sesame oil, soybean oil, safflower oil, avocado oil, sunflower
oil, corn oil, rapeseed oil, cottonseed oil, castor oil, camellia oil,
coconut oil, olive oil, poppy oil, cacao oil, jojoba oil, and like
vegetable oils; beef tallow, lard, wool oil, and like animal oils and
fats; petrolatum, liquid paraffin, squalane, α-olefin oligomer, and like
hydrocarbon liquid oils; isopropyl myristate, isopropyl isostearate,
myristyl myristate, cetyl palmitate, cetyl isooctate, isocetyl myristate,
n-butyl myristate, octyldodecyl myristate, isopropyl linolenate, propyl
ricinoleate, isopropyl ricinoleate, isobutyl ricinoleate, heptyl
ricinoleate, diethyl sebacate, diisopropyl adipate, and like higher fatty
acid esters; white beeswax, whale wax, Japan wax, and like waxes; cetyl
alcohol, stearyl alcohol, behenyl alcohol, batyl alcohol, chimyl alcohol,
and like higher aliphatic alcohols; waxes; stearic acids, oleic acids,
palmitic acids, and like higher fatty acids; mono-, di-, or triglyceride
mixtures of C12-18 saturated or unsaturated fatty acids; methyl
polysiloxane, dimethyl polysiloxane, methylphenyl polysiloxane, methyl
hydrogen polysiloxane, and like linear silicones;
decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane,
methylcyclosiloxane, and like cyclic silicones; crosslinked methyl
polysiloxane, crosslinked methylphenyl polysiloxane, and like crosslinked
silicones; and, for example, silicone oils such as silicones modified by
polyoxyethylene, polyoxypropylene or the like; in addition to others.
Preferable are hydrocarbon liquid oils such as vaseline, liquid paraffin,
squalane, α-olefin oligomer, and the like.
The oils may be used alone or in combination of two or more species. When
oils are solid, it is preferable to liquefy them by means of an auxiliary
resolvent before using.
It is preferable to use the oil in a proportion of 0.3 to 20 wt. % per 100
wt. % of the final emulsion composition, more preferably in a proportion
of 0.5 to 15 wt. %.
Although the preparation method for the O/W emulsion composition is not
limited, it is preferable to prepare it according to the method described
below:
It is preferable to use the polyhydric alcohol in Process (1) for preparing the nonaqueous emulsion in order to further improve the development of the emulsifying ability of the polyglycerin fatty acid ester, the alkanoyl lactylic acid, etc.
Polyhydric alcohols usable herein are not limited. Specific examples include polyglycerins having a polymerization degree of 2 to 10 (for example, diglycerin, triglycerin, tetraglycerin, etc.), ethylene glycol, diethylene glycol, polyethylene glycol, 1,3-buthylene glycol, propylene glycol, dipropylene glycol, isoprene glycol, pentadiol, sorbitol, maltitol, fructose, and the like. The use of glycerin is preferable. These polyhydric alcohols may be used alone or in combination of two or more species. In this case, the polyhydric alcohol is used in a proportion of 0.05 to 15 wt. % per 100 wt. % of the final emulsion composition, preferably in a proportion of 3 to 10 wt. %.
In Process (2), which is for emulsification, a lower alcohol can be incorporated in addition to the electrolyte, the water, and the acrylic acid-alkyl methacrylate copolymer in the aqueous solution (aqueous composition) that is blended with the nonaqueous emulsion. This enhances the percutaneous absorption of the electrolyte. Lower alcohols usable in the invention are not limited, but are usually suitably selected from alcohols having 1 to 6 carbons. Preferable examples are ethanol, propanol, isopropanol, and like C1-4 alcohols. These lower alcohols may be used alone or in combination of two or more species. The use of ethanol is preferable. In this case, the lower alcohol is used in a proportion of 0.5 to 15 wt. % per 100 wt. % of the final emulsion composition, preferably in a proportion of 3 to 10 wt. %.
Moreover, a polyhydric alcohol can be used in the aqueous solution described above (aqueous composition). The use thereby makes it possible to control the moisturizing ability and sensory characteristics of the final emulsion composition to the desired degree. Polyhydric alcohols usable in the aqueous solution include those described above. When a polyhydric alcohol is used in the preparation of the nonaqueous emulsion, it is preferable to use polyhydric alcohols that are identical or highly compatible therewith.
Examples of the method for emulsifying the mixture of the nonaqueous emulsion and the aqueous solution (aqueous composition) include stirring the mixture under atmospheric pressure or high pressure using a homomixer. The particles of the resulting emulsion can be further refined by a homogenizer as required.
The proportion of the nonaqueous emulsion to the aqueous solution (aqueous composition) is not limited. It is usually desirable to control the proportion of the nonaqueous emulsion to 1 to 40 wt. %, preferably 1 to 30 wt. %, based on 100 wt. % of the final emulsion composition, thereby giving a more stable O/W emulsion composition.
The O/W emulsion composition of the invention, insofar as the effects of the invention are not impaired, may contain, as required, a wide range of known substances, such as humectants, UV absorbers, UV dispersants, vitamins, plant extracts, astringents, anti-inflammatory agents, whiteners, antioxidants, cell activators, and especially those known substances used in externally-applied compositions suitable for the skin, such as cosmetics and externally-applied medical/quasi-medical drugs in addition to surfactants, coloring matter (dyes, pigments), aromatics, antiseptic agents, bactericides, thickeners, antioxidants, sequestering agents, pH adjusters, deodorizers, and a wide variety of additives.
The viscosity of the O/W emulsion composition of the invention is not limited. When the O/W emulsion composition is employed as a cosmetic suitable for the skin or as an externally-applied medical or quasi-medical drug, it is usually desirable to prepare the O/W emulsion composition to have a viscosity of 30,000 cps or less, preferably 500 to 20,000 cps, at a temperature of 20° C.
The O/W emulsion composition of the invention stably maintains its emulsified state by inhibiting the oil separation that is typically caused by long-term storage under a condition in which the O/W emulsion composition is likely to be affected by temperature change, even when an electrolyte is contained therein in any amount desired in accordance with the use and the effect intended, especially in any amount desired from the range of 0.1 wt. % or more, preferably 0.1 to 6 wt. %. The O/W emulsion composition of the invention can be prepared, according to the intended use, to provide an excellent, non-tacky feel when used to the skin. The O/W emulsion composition of the invention is therefore especially useful for external preparations, such as cosmetics suitable for the skin (including the scalp), and externally-applied medical and quasi-medical drugs for the skin (including the scalp). Particularly, when adenosine monophosphate (AMP) or the salt thereof is used as an electrolyte, the invention can be prepared as a cosmetic and external preparation for the skin (medical or quasi-medical drug) that is excellent in its moisturizing effect, prevention of dryness and aging, and ability to cure rough skin due to the action of the AMP or the salt thereof.
When the O/W emulsion composition of the invention is prepared as an external preparation such as a cosmetic or an external preparation for skin (medical or quasi-medical drug), the form thereof is not limited. Examples include emulsions, suspensions, creams, and the like.
Examples of cosmetics include emollient emulsions, milky lotions, nourishing emulsions, cleansing emulsions, and like emulsions; emollient creams, massage creams, cleansing creams, makeup creams, and like creams; and the like. These cosmetics are applied to the skin in a suitable amount per application or with a suitable frequency per day, according to the age of the user, the gender, the intended use, the condition of the affected part of the skin, etc.
(2) Method for Stabilizing the Emulsion of an O/W Emulsion Composition Containing an Electrolyte
The present invention also provides a method for stabilizing the emulsion of an O/W emulsion composition containing an electrolyte. This method can be demonstrated by preparing an O/W emulsion composition using an acrylic acid-alkyl methacrylate copolymer, a polyglycerin fatty acid ester, and an alkanoyl lactylic acid or the salt thereof, in addition to an electrolyte, water, and an oil, all of which are as described above. To give higher emulsion stability to the emulsion composition, a polyhydric alcohol may be further added in addition to the ingredients mentioned above.
Specifically, the method can be demonstrated by incorporating the polyglycerin fatty acid ester in a proportion of 0.05 to 6 wt. %, preferably 0.1 to 5.5 wt. %; the alkanoyl lactylic acid or the salt thereof in a proportion of 0.01 to 1 wt. %, preferably 0.1 to 0.5 wt. %; and the acrylic acid-alkyl methacrylate copolymer in a proportion of 0.01 to 0.8 wt. %, preferably 0.3 to 0.6 wt. %, more preferably 0.4 to 0.6 wt. % into 100 wt. % of the final O/W emulsion composition containing the electrolyte in a proportion of 0.1 wt. % or more, preferably 0.5 to 7 wt. %, more preferably 1 to 6 wt. %. In this case, the proportion of the oil contained in the final O/W emulsion composition is not limited, but is preferably 0.3 to 20 wt. %, more preferably 0.5 to 15 wt. %. The water accounts for the portion of the O/W emulsion composition other than that constituted by the oil and other ingredients. The proportion of the water is not limited, but is usually suitably selected from the range of 50 to 90 wt. %, preferably 60 to 80 wt. %.
It is preferable to use the polyglycerin fatty acid ester and the alkanoyl lactylic acid or the salt thereof in such a proportion that the HLB value of the mixture will be 10 or more, preferably 10 to 13. Specifically, it is preferable to use the polyglycerin fatty acid ester and the alkanoyl lactylic acid or the salt thereof in such a proportion that the weight ratio thereof will be 95:5 to 60:40, preferably 90:10 to 70:30.
When a polyhydric alcohol is incorporated, the proportion thereof is, for example, in a range of 0.05 to 15 wt. %, preferably 2 to 10 wt. %.
More specifically, the method of the invention can be demonstrated by using each ingredient in the proportion specified above and then preparing an O/W emulsion composition as described below:
By preparing an O/W emulsion composition as described above, emulsion stability can be given to the O/W emulsion composition, and the oil separation that is typically caused by long-term storage under conditions in which the O/W emulsion composition is likely to be affected by temperature change can be significantly inhibited, thereby providing an emulsion composition that stably maintains its emulsified state.
Claim 1 of 25 Claims
1. An O/W emulsion composition comprising a purine nucleic acid-related
substance, a polyglycerin fatty acid ester, an alkanoyl lactylic acid or
the salt thereof, an acrylic acid-alkyl methacrylate copolymer, water, and
an oil.
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