JP2019119690A - Oil-in-water emulsion composition - Google Patents

Abstract

To provide a heparin analog-containing oil-in-water emulsion composition that is excellent in long-term storage stability as well as in use feeling and moisture retention effect during its application.SOLUTION: An oil-in-water emulsion composition contains following components (A), (B), (C), (D) and (E) with a 30°C pH of 4.5-7.0: (A) a heparin analog 0.05 mass% or more and 0.6 mass% or less; (B) hydrophobized hydroxypropyl methylcellulose 0.01 mass% or more and 0.5 mass% or less; (C) oil solution; (D) a surfactant; (E) water.SELECTED DRAWING: None

Description

  The present invention relates to an oil-in-water emulsion composition useful as a skin external preparation.

  Heparin analogues have pharmacological actions such as moisturizing action, anti-inflammatory action, etc. The efficacy and effects of external skin preparations formulated with them are thrombophlebitis (including hemorrhoid), pain based on blood circulation disorder and inflammatory disease (Induration and pain after injection), frostbite, treatment and prevention of hypertrophic scars and keloids, progressive digital palmar keratoderma, cortical deficiency, swelling, hematoma, tendonitis, myalgia after trauma (pulp, sprain, contusion)・ It is considered as arthritis, muscular tore (in infancy). And, as a dosage form of the heparin analogue-containing external skin preparation, a cream, a soft ointment, and a lotion are sold.

  Among these dosage forms, creams and lotions, which are oil-in-water emulsion compositions, are widely used because they have a better feel than ointments. However, oil-in-water emulsion compositions containing heparin analogues are not stable in emulsification system over time and tend to cause oil-water separation. Therefore, a technology to stabilize an oil-in-water emulsion system by using a carboxyvinyl polymer and a cellulose ether derivative in combination with a heparin analogue (Patent Document 1), and combining a carboxyvinyl polymer and vegetable wax or fat with a heparin analogue A technology for stabilizing oil-in-water emulsion systems (Patent Document 2) and a technology for improving rough skin conditions by combining heparin analogues and betaines (Patent Document 3) have been reported.

Unexamined-Japanese-Patent No. 2010-70523 JP, 2011-93895, A JP 2000-143486 A International Publication No. 2011/162421 pamphlet

However, although the above-described heparin analogue-containing oil-in-water emulsion composition has improved the emulsion stability to a certain extent, the carboxyvinyl polymer and the betaines cause stickiness and the like, and there is a problem in use feeling. Furthermore, there is also a problem that the feeling of effectiveness of moisturizing which is the original effect of heparin analogues is not sufficient.
Therefore, an object of the present invention is to provide a heparin analogue-containing oil-in-water emulsion composition which is excellent not only in long-term storage stability but also in use feeling and moisturizing effect at the time of application.

  Therefore, when the present inventor produced an oil-in-water emulsion composition containing heparin analogues and variously examined its stability, feeling in use, and moisturizing effectiveness, the heparin analogue-containing oil-in-water emulsion composition When hydrophobized modified alkylcellulose (described in Patent Document 4) is added to the composition and the pH of the composition is adjusted to 4.5 to 7.0, the storage stability is quite unexpectedly improved, and the feeling in use and the moisturizing effect are achieved. The present invention has been completed by finding that an oil-in-water emulsion composition having excellent properties can be obtained.

That is, the present invention comprises an oil-in-water emulsion which contains the following components (A), (B), (C), (D) and (E) and has a pH of 4.5 to 7.0 at 30 ° C. It provides a composition.
(A) Heparin analogue 0.05 mass% or more and 0.6 mass% or less (B) hydrophobized hydroxypropyl methylcellulose 0.01 mass% or more and 0.5 mass% or less (C) oil agent (D) surfactant (E )water

  The heparin analogue-containing oil-in-water emulsion composition of the present invention not only has good storage stability, but also has a smooth feel upon application, less irritation, good feeling in use, and moisturizing effectiveness. Is significantly better.

  The oil-in-water emulsion composition of the present invention is characterized by containing (A) heparin analogue and (B) hydrophobized hydroxypropyl methylcellulose, and having a pH of 4.5 to 7.0 at 30 ° C.

The heparin analogue of component (A) is a substance also known as mucopolysaccharide polysulfate or heparinoid, and is a sulfated mucopolysaccharide having a repeating disaccharide structure of D-glucuronic acid and N-acetyl-D-galactosamine. It is a thing. As a heparin analogue, the heparin analogue described in Japanese Pharmacopoeia Standard 2002 is preferable.
The average molecular weight of the heparin analogue is not particularly limited, but from the viewpoint of medicinal effects such as moisturizing action, 1000 to 1000000 Mw is preferable, and 5000 to 100000 Mw is particularly preferable. The amount (%) of the organic sulfate group in the heparin analogue is not particularly limited, but it is preferably 20 to 40%, particularly preferably 25 to 38%, from the viewpoint of medicinal effects such as moisturizing action. The amount of the organic sulfate group is measured by the method described in the section of "Heparin-like substance" in the Pharmaceutical Standards for Non-Japanese Pharmacopoeia 2002.

  The content of the component (A) in the oil-in-water emulsion composition of the present invention is preferably 0.05% by mass or more from the viewpoints of medicinal effects such as moisturizing action, storage stability, feeling in use, etc. % By mass or more is more preferable, 0.1% by mass or more is further preferable, 0.2% by mass or more is further more preferable, and 0.6% by mass or less is preferable, 0.5% by mass or less is more preferable, 0 .4 mass% or less is further preferable, and 0.35 mass% or less is still more preferable. Specifically, 0.05% by mass or more and 0.6% by mass or less is preferable, 0.07% by mass or more and 0.5% by mass or less is more preferable, 0.1% by mass or more and 0.4% by mass or less Preferably, 0.2% by mass or more and 0.35% by mass or less is more preferable.

The hydrophobized hydroxypropyl methylcellulose of the component (B) is a compound obtained by introducing a long chain alkyl group which is a hydrophobic group into hydroxypropyl methylcellulose which is a cellulose ether derivative, and is a compound described in Patent Document 4, for example. By using this hydrophobized hydroxypropyl methylcellulose, a remarkably superior moisturizing effect can be obtained as compared to the case of using conventional hydroxypropyl methylcellulose and methylcellulose.
As a long chain alkyl group, a C ₈ -C ₂₄ alkyl group is preferable, a C ₁₀ -C ₂₀ alkyl group is more preferable, a lauryl group, a myristyl group, a palmityl group, and a stearyl group are more preferable, and a stearyl group is still more preferable.
As hydrophobized hydroxypropyl methylcellulose, hydroxypropyl methylcellulose C ₈ -C ₂₄ alkyl ether is preferable from the viewpoint of storage stability of an oil-in-water emulsion composition, feeling in use, and moisturizing effect, hydroxypropyl methylcellulose C ₁₀ -C ₂₀ Alkyl ethers are more preferred, and hydroxypropyl methylcellulose stearyl ether is even more preferred.

(B) As hydrophobized hydroxypropyl methylcellulose, 0.5% water / 2-propanol (119/80 (wt / wt) from the viewpoint of storage stability of the oil-in-water emulsion composition, feeling in use, and moisturizing effectiveness. ) The mixed solution preferably has a viscosity of 72 to 240 mm ² / s at 25 ° C., and more preferably 160 to 240 mm ² / s. Here, the viscosity is the viscosity described in the section of "Additional hydrophobized hydroxypropyl methylcellulose" of the pharmaceutical additive standard 2013 of the pharmaceutical additive specification 2013.

  The content of the component (B) in the oil-in-water emulsion composition of the present invention is preferably 0.01% by mass or more, more preferably 0.02% by mass or more, from the viewpoint of storage stability, feeling in use, and moisturizing effectiveness. Preferably, 0.03% by mass or more is more preferable, 0.05% by mass or more is further preferable, 0.1% by mass or more is more preferable, 1% by mass or less is preferable, and 0.8% by mass or less is more preferable 0.6% by mass or less is more preferable, 0.5% by mass or less is more preferable, 0.4% by mass or less is more preferable, 0.3% by mass or less is more preferable, and 0.2% by mass or less is even more preferable. Specifically, 0.01% by mass or more and 1% by mass or less is preferable, 0.01% by mass or more and 0.5% by mass or less is preferable, 0.02% by mass or more and 0.4% by mass or less is more preferable, 0 More preferably, .03 mass% or more and 0.3 mass% or less, still more preferably 0.05 mass% or more and 0.2 mass% or less, and still more preferably 0.1 mass% or more and 0.2 mass% or less.

  The mass ratio (A / B) of the component (A) to the component (B) in the oil-in-water emulsion composition of the present invention is preferably 0.5 or more from the viewpoint of storage stability, feeling in use and moisturizing effectiveness. 0.8 or more is more preferable, 1 or more is further preferable, 1.5 or more is further more preferable, 10 or less is preferable, 5 or less is more preferable, and 3 or less is even more preferable. Specifically, 0.5 or more and 10 or less are preferable, 0.8 or more and 5 or less are more preferable, 1 or more and 5 or less are more preferable, and 1.5 or more and 3 or less are more preferable.

  The oil-in-water emulsion composition of the present invention having a pH of 4.5 to 7.0 at 30 ° C. is important for obtaining storage stability, good feeling in use and moisturizing effectiveness. When the pH is less than 4.5, the storage stability is not sufficient, and when the pH is more than 7.0, the usability and the moisturizing effectiveness are not sufficient. The preferred pH range is 4.5 or more and 6.5 or less, more preferably 4.8 or more and 6.0 or less, more preferably 5.0 or more and 6.0 or less, and still more preferably 5. It is 0 or more and 5.8 or less.

  In order to adjust the pH of the oil-in-water emulsion composition to 4.5 to 7.0, a pH adjuster such as an acid and / or a base is preferably contained. Specifically, an organic acid or an inorganic acid capable of adjusting pH to 4.5 to 7.0 is used, and an organic acid is more preferable from the viewpoint of feeling in use, stability, and feeling of effective moisturizing. Examples of the organic acid include succinic acid, citric acid, gluconic acid, lactic acid and malic acid.

  The oil-in-water emulsion composition of the present invention preferably contains (C) oil agent, (D) surfactant and (E) water, which are components forming the oil-in-water emulsion composition, in addition to the above components. . The content of water is not particularly limited as long as it is an amount capable of forming an oil-in-water emulsion system, but 40% by mass to 90% by mass is preferable, and 55% by mass to 80% by mass is more preferable. 65 mass% or more and 75 mass% or less are more preferable.

As an oil agent, solid oil is also mentioned other than liquid oil, and it is preferable to contain liquid oil and solid oil. The liquid oil is not particularly limited as long as it is a liquid oil at 25 ° C., for example, hydrocarbon oils such as liquid paraffin, squalane and vaseline; ethers such as cetyl dimethyl butyl ether, ethylene glycol dioctyl ether and glycerol monooleyl ether Oils: Ester oils such as vegetable oils such as octyldodecyl myristate, isopropyl palmitate, butyl stearate, di-2-ethylhexyl adipate, neopentyl glycol dicaprate, trioctanoin, olive oil etc .; dimethylpolysiloxane, cyclic dimethylpolysiloxane Methylphenylpolysiloxane, amino-modified silicone, carboxy-modified silicone, alcohol-modified silicone, alkyl-modified silicone, polyether-modified silicone, fluorine-modified silicone Silicone oils and the like; perfluoroalkylethyl phosphoric acid, perfluoroalkyl polyoxyethylene phosphoric acid, a perfluoropolyether, such as fluorine-based oils such as polytetrafluoroethylene.
These liquid oils can be used alone or in combination of two or more. From the viewpoint of storage stability and feeling of use, the content is preferably 1% by weight or more, and 20% by weight or less in the whole composition. Preferably, 15% by weight or less is more preferable. Moreover, 1-20 weight% is preferable in a whole composition, as for content of liquid oil, 1-15 weight% is more preferable, and 3-5 weight% is more preferable.

The solid oil is a solid oil agent at 25 ° C., and includes higher alcohols, higher fatty acids, hydrocarbon oils such as vaseline, etc. Among them, the use of higher alcohols provides a high moisturizing effect, stability Preferred in terms of Examples of higher alcohols include myristyl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, cholesterol, phytosterol and the like, and aliphatic alcohols having 16 to 18 carbon atoms are preferable, and cetyl alcohol and stearyl alcohol are more preferable.
These solid oils, particularly higher alcohols, may be used alone or in combination of two or more and are preferably contained in an amount of 0.05% by mass or more and 6% by mass or less in the whole composition, 0.1% by mass or more and 5% by mass % Or less is more preferable, 0.5 mass% or more and 3.5 mass% or less is more preferable, 0.5 mass% or more and 1.8 mass% or less is still more preferable, and 0.7 mass% or more and 1.0 mass% The following are more preferable.

  In the present invention, it is more preferable to use a liquid oil and a higher alcohol as an oil agent in combination, from the viewpoint of causing the oil-in-water emulsion composition to form a lamellar α-gel structure and exerting a higher moisturizing effect.

The surfactant may be any surfactant as long as it can stably emulsify the component and the oil agent, and one or more selected from nonionic surfactants, anionic surfactants and amphoteric surfactants. It is preferable to use 2 or more types. Here, as the nonionic surfactant, for example, sorbitan fatty acid ester such as sorbitan monostearate, glycerin fatty acid ester such as glycerin monostearate, polyglycerin fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol fatty acid ester, sucrose Polyoxyethylene sorbitan fatty acid esters such as fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene monostearate (20) sorbitan (polysorbate 60), polyoxyethylene alkyl ether, alkyl glyceryl ether, polyoxyethylene sorbitol fatty acid ester, poly Oxyethylene glycerine fatty acid ester, polyoxyethylene propylene glycol fatty acid ester, polyoxyethylene ethylene glycol Silicone oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil fatty acid ester, polyoxyethylene phytostanol ether, polyoxyethylene phytosterose ether, polyoxyethylene cholestanol ether, polyoxyethylene cholesteryl ether, polyoxyalkylene Modified organopolysiloxanes, polyoxyalkylene / alkyl co-modified organopolysiloxanes, etc. may be mentioned.
Among them, sorbitan fatty acid ester, glycerin fatty acid ester, alkyl glyceryl ether and polyoxyethylene sorbitan fatty acid ester are preferable from the viewpoint of emulsion stability, feeling in use and feeling of moisturizing effect. Further, sorbitan fatty acid ester having 12 to 22 carbon atoms, glycerin monocarbon fatty acid ester having 12 to 22 carbon atoms, alkyl glyceryl ether having 12 to 22 mono carbon atoms, and polyoxyethylene sorbitan fatty acid ester having 12 to 22 carbon atoms are preferable.
Examples of amphoteric surfactants include phospholipids, and among phospholipids, soybean phospholipid and hydrogenated soybean phospholipid are preferable.

  As the anionic surfactant, for example, a fatty acid having 12 to 22 carbon atoms such as sodium laurate, potassium palmitate, arginine stearate or a salt thereof; and 12 to 22 carbon atoms such as sodium lauryl sulfate and potassium lauryl sulfate Alkyl sulfates or salts thereof; alkyl ether sulfates having 12 to 22 carbon atoms such as polyoxyethylene lauryl sulfate triethanolamine etc. or salts thereof; acylsarcosines having 12 to 22 carbons such as sodium lauroyl sarcosine or salts thereof; Alkyl phosphoric acid having 12 to 22 carbon atoms such as sodium monostearyl phosphate or a salt thereof; polyoxyethylene cetyl ether sodium phosphate, polyoxyethylene oleyl ether sodium phosphate, polyoxyethylene stearyl ether sodium phosphate Polyoxyethylene having 12 to 22 carbon atoms such as C. 22-22 or a salt thereof; C.sub.12-24 dialkyl sulfosuccinic acid such as sodium di-2-ethylhexyl sulfosuccinate or a salt thereof; N-stearoyl-N-methyl C 12-22 N-alkyloyl methyl taurine or its salts such as sodium taurine; dilauroyl glutamate sodium, N-lauroyl glutamate monosodium, N-stearoyl-L-glutamate sodium, N-stearoyl-L-glutamate arginine, Acyl glutamic acid having 12 to 22 carbon atoms or a salt thereof such as sodium N-stearoylglutamate, sodium N-myristoyl-L-glutamate and the like can be mentioned. Among these, fatty acids having 12 to 22 carbon atoms or salts thereof, polyoxyethylene alkyl ether phosphoric acids having 12 to 22 carbon atoms or salts thereof, N-alkyloyl methyl taurine having 12 to 22 carbon atoms or salts thereof, N- C12-22 acyl glutamic acid or a salt thereof is preferred.

  Among these surfactants, it is preferable to use two or more nonionic surfactants in combination, or to use a nonionic surfactant and an anionic surfactant in combination, in which the composition is lamellar α- It is preferable from the viewpoint of forming a gel constitution and exerting a higher moisturizing effect, and it is more preferable to use a nonionic surfactant and an anionic surfactant in combination. Among them, it is more preferable to use two or more nonionic surfactants in combination with anionic surfactants.

  The content of the surfactant in the oil-in-water emulsion composition of the present invention is 0.02 mass in total from the viewpoint of stabilization of the emulsion system, lamellar α-gel formation ability, improvement of moisturizing effect, and feeling of use. % To 6% by mass is preferable, 0.05% to 5% by mass is more preferable, 0.1% to 3% by mass is further preferable, and 0.5% to 2% by mass is further preferable .

  The oil-in-water emulsion composition of the present invention contains (G) an amphiphilic component, (F) a polyhydric alcohol, an antiseptic agent, an extract, a flavor and the like from the viewpoint of improving the moisturizing effect and feeling of use. Can.

  Examples of amphiphilic components include ceramides, monoglycerin difatty acid esters and sorbitan difatty acid esters. The ceramides include natural ceramides and pseudo-ceramides represented by the general formula (1).

(Wherein, R ¹ represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having a carbon number of 10 to 22, which may be substituted with a hydroxyl group, or a hydrogen atom; and X ¹ represents a hydrogen atom) And R ² represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 5 to 22 carbon atoms which may be substituted by a hydroxyl group or an amino group, or an acetyl group or a glyceryl group; Or the ω-terminal of the hydrocarbon group is an ester bond of a linear or branched saturated or unsaturated fatty acid having 8 to 22 carbon atoms which may be substituted by a hydroxyl group; R ³ is a hydrogen atom Or an alkyl group having 1 to 30 carbon atoms in total that may be substituted with a hydroxyl group, a hydroxyalkoxy group, an alkoxy group or an acetoxy group.)

R ² is nonyl, tridecyl, pentadecyl, an undecyl group in which linoleic acid is ester bonded in the ω position, a pentadecyl group in which linoleic acid is ester bonded in the ω position, a pentadecyl group in which 12-hydroxystearic acid is ester bonded in the ω position, An undecyl group in which methyl branched isostearic acid is amide-bonded to the ω position is preferable.

When R ¹ is a hydrogen atom, R ³ is an alkyl group having 10 to 30 carbon atoms in total, preferably 12 to 20 carbon atoms, which may be substituted by a hydroxyl group, a hydroxyalkoxy group, an alkoxy group or an acetoxy group. When R ¹ is a linear, branched or cyclic, saturated or unsaturated hydrocarbon group having 10 to 22 carbon atoms which may be substituted by a hydroxyl group, R ³ represents a hydrogen atom, or hydroxyl It is preferable to show an alkyl group having 1 to 8 carbon atoms in total, which may be substituted by a group, a hydroxyalkoxy group, an alkoxy group or an acetoxy group. As a hydroxy alkoxy group or alkoxy group of R ³ , one having 1 to 7 carbon atoms is preferable.

In the general formula (1), R ¹ is a hexadecyl group, X ¹ is a hydrogen atom, R ² is a pentadecyl group, R ³ is a hydroxyethyl group; R ¹ is a hexadecyl group, X ¹ is a hydrogen atom, and R ² is The pseudo type ceramide in which nonyl group and R ³ are hydroxyethyl group is preferable, and R ^{1 in the} general formula (1) is hexadecyl group, X ¹ is hydrogen atom, R ² is pentadecyl group, and R ³ is hydroxyethyl group ( N- (hexadecyloxyhydroxypropyl) -N-hydroxyethyl hexadecanamide) is more preferred.

  As natural ceramides, ceramide I, ceramide III, ceramide IIIA, ceramide IIIB, ceramide IIIC, ceramide VI (above, Cosmofarm Co., Ltd.), Ceramide TIC-001 (Takasago perfume company), CERAMIDE II (Quest International Co.), DS-Ceramide VI, DS-CLA-Phytoceramide, C6-Phytoceramide, DS-ceramide Y3S (DOOSAN), CERAMIDE 2 (Cedama).

  The content of the ceramides in the composition of the present invention is preferably 0.2% by mass or more and 15% by mass or less, more preferably 0.4% by mass or more and 12% by mass or less, from the viewpoint of obtaining a high moisturizing effect. 7 mass% or more and 5 mass% or less are more preferable, 1 mass% or more and 4 mass% or less are more preferable, and 2 mass% or more and 4 mass% or less are more preferable.

As the monoglycerin difatty acid ester, monoglycerin dicarbon fatty acid ester having 12 to 22 carbon atoms is preferable. For example, glycerin dilaurate, glycerin dimyristate, glycerin dipalmitate, glycerin distearate, glycerin dibehen Examples thereof include acid esters, glycerine dioleate, and glycerine diisostearate.
As the sorbitan difatty acid ester, fatty acid esters having sorbitan dicarbon number of 12 to 22 are preferable. For example, sorbitan dilaurate, sorbitan dimyristate, sorbitan dipalmitate, sorbitan distearate, sorbitan dibehenate, sorbitan dioleate, etc. Be
Among these, glycerin distearate and sorbitan distearate are preferable in terms of storage stability.

  The content of these diesters in the composition of the present invention is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, and further preferably 1% by weight or more from the viewpoint of stability and feeling in use. preferable. Moreover, 14.8 weight% or less is preferable, 5 weight% or less is more preferable, 3.2 weight% or less is more preferable. Specifically, 0.1 to 14.8% by weight is preferable, 0.5 to 5% by weight is more preferable, and 1 to 3.2% by weight is more preferable.

  The polyhydric alcohol is not particularly limited as long as it is used in ordinary cosmetics. For example, glycerin, 1,3-butylene glycol, 1,3-propanediol, propylene glycol, diglycerin, dipropylene glycol, molecular weight 2000 or less polyethylene glycol etc. are mentioned. Among them, at least one selected from glycerin, 1,3-butylene glycol and dipropylene glycol is preferable from the viewpoint of feeling in use, at least one selected from glycerin and 1,3-butylene glycol is more preferable, and glycerin is preferred. More preferable.

  Polyhydric alcohol can be used combining 1 type, or 2 or more types, 5-30 mass% is preferable in a whole composition, 7-30 mass% is more preferable, 10-20 mass% is preferable in content. Is more preferred.

  The viscosity at 30 ° C. of the oil-in-water emulsion composition of the present invention is preferably 8 to 200 Pa · s, preferably 10 to 200 Pa · s, and 20 to 150 Pa · s from the viewpoint of emulsion stability, storage stability, and feeling of use. s is more preferable, and 60 to 120 Pa · s is more preferable. The viscosity was measured at 30 ° C. using a Brookfield viscometer and a rotor with the smallest number of revolutions at each viscosity.

  The oil-in-water emulsion composition of the present invention can be produced, for example, by heating and mixing an oil phase component and a surfactant as required, and then adding and emulsifying an aqueous phase component.

  The oil-in-water emulsion composition of the present invention contains heparin analogues in a stable manner and has a good feeling in use and excellent moisturizing effect. It is useful as a skin external preparation for improvement.

  The present invention will now be described in more detail by way of examples.

Examples 1 to 10 and Comparative Examples 1 to 5
The oil-in-water emulsion compositions shown in Table 1 and Table 2 were produced, and storage stability, smoothness upon application, and moisturizing effect were evaluated. In addition, the presence of aggregates and the feeling of irritation upon application were also evaluated by microscopic observation. The results are shown in Tables 1 and 2.

(Production method)
With respect to the oil phase obtained by dissolving the oil phase components shown in Tables 1 and 2 at 75 to 95 ° C., the aqueous phase obtained by uniformly dissolving the water phase components shown in Tables 1 and 2 under stirring with a homomixer (7000 r / m) The mixture was gradually added and emulsified, and cooled to 30 ° C. to produce an oil-in-water emulsion composition.

(Evaluation method)
(1) Storage stability (1)
The state of the composition after 1 month storage at 50 ° C. was visually evaluated according to the following criteria.
A: No change B: Slight change in viscosity C: Clear change in viscosity D: Partial separation or gelation E: Whole separation or gelation (1) Storage stability (2)
The viscosity of each oil-in-water emulsion composition which was placed at 25 ° C. for 24 hours after production was measured at 30 ° C., and was defined as an initial viscosity. The viscosity was measured using a Brookfield viscometer using a rotor with the smallest number of revolutions at each viscosity. The composition was then ramped up gradually from -20 ° C to 60 ° C over 12 hours at a uniform rate, and then similarly from 60 ° C to -20 ° C, and a temperature cycle was set up with one reciprocation per day. After storing for 6 days under storage conditions and returning to 25 ° C., the viscosity after storage at 30 ° C. was measured. The value obtained by dividing the viscosity after storage by the initial viscosity was expressed as a percentage of viscosity change. In addition, what was clearly separated by visual observation did not measure a viscosity, and described it as "separation" in evaluation. Those which are not separated are good, and in particular, those having a viscosity change rate close to 100 are good.

(2) Smoothness at the time of application Ten expert panelists sensory-evaluated the smoothness at the time of applying each emulsified composition, and the following criteria were judged.
A: 7 to 10 evaluated as good (good) B: 5 or 6 evaluated as good (good) C: 3 or 4 evaluated as good (good) D: 1 or 2 Good (Good) Evaluation E: No panelists rated Good (good)

(3) Moisturizing Effective Sense Ten specialized panelists performed sensory evaluation on the moisturizing effective feeling when using each emulsified composition, and were judged according to the following criteria.
A: Evaluation that 7 to 10 people feel moisturized B: Evaluation that 5 or 6 people feel moisturized C: Evaluation that 3 or 4 people feel moisturized D: Evaluation that one or two people feel moisturized E: No panelists who evaluated that they felt moisturized

(4) Microscopic Observation The emulsified composition immediately after production was observed with an optical microscope (20 ×) and visually evaluated according to the following criteria.
A: Only homogeneous emulsified particles are observed B: Aggregates having a particle diameter of 2 times or more of the emulsified particles are observed C: Many aggregates having a particle diameter of 2 times or more of the emulsified particles are observed Some aggregates with a particle size of 10 times or more are seen D: Many aggregates with a particle size of 10 times or more of the emulsified particles are seen E: Only aggregates are seen or can not be emulsified

(5) Stimulus at the time of application Ten expert panelists sensory-evaluated a weak stimulus at the time of applying each emulsified composition, and were judged according to the following criteria.
A: 7 to 10 evaluated without stimulation B: 5 or 6 evaluated without stimulation C: 3 or 4 evaluated without stimulation D: 1 or 2 no stimulation Evaluation E: Evaluation that everyone has a stimulus

* 1: Sangerose 90L (made by Daido Chemical Industries, Ltd.)
* 2: Sangerose 60 L (made by Daido Chemical Industries, Ltd.)
* 3: METOLOSE SM (Shin-Etsu Chemical Co., Ltd.)
* 4: METOLOSE 60SH (Shin-Etsu Chemical Co., Ltd.)
* 5: Amisoft GS-11P (made by Ajinomoto Co.)
* 6: Amisoft LS-11 (manufactured by Ajinomoto Co.)
* 7: Courtsome NC-21 (made by NOF Corporation)

Claims (12)

An oil-in-water emulsion composition containing the following components (A), (B), (C), (D) and (E) and having a pH of 4.5 to 7.0 at 30 ° C.
(A) Heparin analogue 0.05 mass% or more and 0.6 mass% or less (B) hydrophobized hydroxypropyl methylcellulose 0.01 mass% or more and 0.5 mass% or less (C) oil agent (D) surfactant (E )water   The oil-in-water emulsion composition according to claim 1, wherein the pH at 30 ° C is 5.0 to 5.8.   The oil-in-water emulsion composition according to claim 1 or 2, wherein the content of the component (A) is 0.1% by mass or more and 0.4% by mass or less. Component (B), oil-in-water emulsified composition of any one of claims 1 to 3, containing hydroxypropyl methylcellulose C ₈ -C ₂₄ alkyl ether. The viscosity at 25 ° C. of a 0.5% water / 2-propanol (119/80 (wt / wt)) mixed solution of component (B) is 72 to 240 mm ² / s 5. An oil-in-water emulsion composition as described in the above item.   Content of component (B) is 0.1 mass% or more and 0.2 mass% or less, The oil-in-water type emulsion composition of any one of Claims 1-5.   The oil-in-water emulsion composition according to claim 6, wherein the component (C) contains a liquid oil and a solid oil.   The oil-in-water emulsion composition according to any one of claims 1 to 7, wherein the component (D) contains two or more nonionic surfactants.   Furthermore, the oil-in-water type emulsion composition of any one of Claims 1-7 containing a polyhydric alcohol as a component (F).   The oil-in-water emulsion composition according to any one of claims 1 to 9, further comprising an amphiphilic component as the component (G).   The oil-in-water emulsion composition according to any one of claims 5 to 10, wherein the component (G) contains a ceramide.   The oil-in-water emulsion composition according to any one of claims 1 to 11, which is a skin external preparation.