JP2001151938A - W/o/w type complex emulsion - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a W/O/W type complex emulsion that maintains excellent properties for a long time, especially restoration behavior in characteristics at defreezing and feel at use, and is useful for medical applications cosmetic preparations, etc. SOLUTION: This W/O/W type complex emulsion is characterized in that the ratio of the W/O type emulsion to the outer water phase lies in the range of from 30/70 to 80/20 (mass ratio), wherein the W/O type emulsion has an inner water phase comprising a polysaccharide with a sulfonic group and/or a carboxyl group in a molecule and an oil phase at a ratio of 50/50 to 90/10 (mass ratio). As the polysaccharide, an acidic mucopolysaccharide, especially chondroitin 4-sulfate, heparin, a heparin-like substance, iota-carrageenan, hyaluronic acid are preferable.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a W / O / W composite emulsion useful as a pharmaceutical or cosmetic preparation.

2. Description of the Related Art In order to form a W / O / W type composite emulsion, it is necessary to prepare a W / O type emulsion as a dispersoid and then redisperse the W / O type emulsion in an external aqueous phase. is there. However, during the redispersion process, a part of the oil phase of the W / O emulsion is solubilized by the hydrophilic surfactant in the external aqueous phase, so that the W / O emulsion is easily broken, and as a result stable It was difficult to obtain a W / O / W type composite emulsion having excellent properties at a high production rate. Conventionally, in order to prevent such phase inversion during the redispersion process (secondary emulsification), W / O emulsion (W ≦ O) in which the ratio of the oil phase to the internal aqueous phase was increased by primary emulsification Was essential. However, when a W / O emulsion in which the ratio of the oil phase to the internal aqueous phase is increased is used, there is a problem that sticky feeling is generated and the original feeling of use of the W / O / W type is impaired. Further, the W / O / W type composite emulsion is not only difficult to prepare at a high production rate, but also has a problem that the long-term stability, particularly the freeze-recoverability, is extremely poor. Conventionally, several methods for stabilizing a W / O / W type composite emulsion have been proposed, but there has been no means for simultaneously solving a good feeling in use and long-term stability, especially freeze-recoverability.
That is, as a conventional example of producing a W / O / W type composite emulsion at a high production rate, composite particles (W / O particles)
Japanese Patent Application Laid-Open No. 58-18361 discloses a method for preventing coalescence between two members.
1 describes a method of using a water-soluble polysaccharide as a thickener in an external aqueous phase. However, this method does not prevent coalescence of the internal aqueous phases, is insufficiently stabilized, and further increases the viscosity, which impairs the feeling of use and is not practical. Also, Japanese Patent Application Laid-Open No. Hei 7-118306 discloses W
An / O emulsion composition is disclosed. However, this method is not practical because of not only insufficient long-term stability (maintaining the viscosity of the emulsion) but also a sticky feeling because the external phase is oil. Further, JP-A-62-2271
No. 2 discloses a W / O / W containing one or more selected from monosaccharides, disaccharides, polysaccharides and polyhydric alcohols in an inner aqueous phase.
An emulsified perfume composition is disclosed. However, in this method, a large amount of the above components must be blended for stabilization, which is not practical.

[0002]

DISCLOSURE OF THE INVENTION The present invention provides a W / O / W type composite emulsion which is excellent in long-term stability, in particular, freeze-recoverability and feeling upon use.

Means for Solving the Problems The present invention provides a stable high water content W / W which is hardly destroyed by secondary emulsification by blending a polysaccharide having a sulfone group and / or a carboxyl group in a molecule into an internal aqueous phase. It has been found that the preparation of an O-type emulsion is possible, and by using the W / O-type emulsion as a dispersoid, long-term stability, particularly W / O / W excellent in freeze-recoverability.
It has been found that a type composite emulsion can be obtained at a high production rate. That is, the present invention provides a W / O / W type composite emulsion comprising a polysaccharide having a sulfone group and / or a carboxyl group in a molecule in an internal aqueous phase.

[0003]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The main monosaccharides constituting the polysaccharide of the present invention include D-glucosamine, D-galactosamine,
-Glucuronic acid, L-iduronic acid, D-glucose, D-galactose, D-xylose and the like. The polysaccharide of the present invention is a polymer of one or more monosaccharides, and a sulfone group or a carboxyl group has an average of 0.4 to 5 per molecule of the monosaccharide.
Preferably, the molecule is contained, more preferably 0.5 to 3 molecules, still more preferably 0.6 to 2 molecules. The average molecular weight of the polysaccharide of the present invention is preferably 1,000
~ 10,000,000, more preferably 3,000 ~ 1,000,000, even more preferably 5,000 ~ 500,000.

[0004] Examples of such polysaccharides include hyaluronic acid, chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, keratan sulfate, heparin, heparin-like substances (listed in Japanese Pharmacopoeia outside the Japanese Pharmacopoeia), kappa and iota. Or acid mucopolysaccharides such as lambda-carrageenan and dervillea; and sulfated neutral mucopolysaccharides such as chitin. Of these, acidic mucopolysaccharides are preferred, and chondroitin 4-sulfate, heparin, heparin-like substances, iota-carrageenan, and hyaluronic acid are particularly preferred. The polysaccharide of the present invention can be used irrespective of natural products and synthetic products, and can be used alone or in combination of two or more. The compounding amount of the polysaccharide of the present invention is preferably 0.02 to 3%, more preferably 0.2 to 2%, based on the total mass of the internal aqueous phase.
%, More preferably 0.7 to 1.5%. W / of the present invention
It is preferably 0.01 to 2%, more preferably 0.03 to 1.5%, and still more preferably 0.05 to 1%, based on the total mass of the O / W type composite emulsion.

[0005] As the oil phase of the present invention, liquid paraffin,
Vaseline, microcrystalline wax, hydrocarbons such as squalane, olive oil, safflower oil, soybean oil,
Vegetable oils such as almond oil and castor oil; animal solid waxes such as beeswax, spermaceti and lanolin; fatty acid esters such as isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, and tri (caprylic / capric acid) glycerin; As long as it is used for external preparations and cosmetics, it can be used without any particular limitation. The W / O / W type composite emulsion of the present invention can be preferably produced by the following method. Primary emulsification An internal aqueous phase component solution (preferably containing an active ingredient) containing a polysaccharide having a sulfone group and / or a carboxyl group in the molecule and an oil phase component solution (preferably containing a lipophilic surfactant) ) At 65-85 ° C, particularly preferably 7
Heat to 0-80 ° C to uniformly dissolve each. After dissolution, the internal water phase / oil phase = 50/50 to 90/10, preferably 60/40 to 85/15, more preferably 65/15 while stirring the oil phase component under the same temperature conditions with a homomixer or the like.
The internal aqueous phase is slowly added so as to have a mass ratio of / 35 to 80/20 to prepare a W / O emulsion. The stirring conditions are appropriately selected depending on the size of the stirring blade and the emulsified composition, but it is preferable to emulsify at a rotation speed of about 3000 to 6000 rpm for 5 to 20 minutes. Since the electric conductivity of the emulsion is almost zero (the external phase is oil), W
Confirm the formation of / O emulsion.

Secondary emulsification The aqueous emulsion (preferably containing a hydrophilic surfactant) is obtained under stirring at a temperature of 45 to 70 ° C., particularly preferably 50 to 65 ° C., with a homomixer or the like. W
/ O type emulsion, W / O type emulsion / outer aqueous phase = 30 / 70-80 / 20, preferably 40 / 60-7.
0/30, more preferably 45/55 to 60/40 by mass, to the external aqueous phase.
2. Prepare a complex emulsion. The emulsification conditions are preferably selected as appropriate so as not to destroy the composite particles once formed, but are generally 20 rpm at a rotation speed of 500 to 3000 rpm.
It is preferred to emulsify for ~ 90 minutes. According to the configuration of the present invention, it is possible to increase the water content of the internal aqueous phase. The mixing mass ratio of the internal water phase and the oil phase of the W / O emulsion as the dispersoid is such that the internal water phase / the oil phase is preferably 50/50 to 90/10, more preferably 60/40 to 85/15, More preferably 70/30 to 80
/ 20 is desirable. This range is preferable because a feeling of use of the preferred preparation can be obtained. The mass ratio of the W / O emulsion to the external aqueous phase as the dispersion medium is W / O emulsion / external aqueous phase = preferably 30/70 to 80/20, more preferably 40/60.
7070/30, more preferably 45 / 55-60 / 40. This range is preferable because the production rate and stability of the emulsion of the present invention are good. The ratio of the internal aqueous phase is preferably 15 to 75%, more preferably 25 to 60%, and still more preferably 30 to 50%, based on the whole W / O / W composite emulsion of the present invention. The total amount of the inner aqueous phase and the outer aqueous phase is preferably 70 to 95%, more preferably 75 to 93%, and still more preferably 80 to 90%. This range is preferable because the emulsion is good. In this specification, “%” indicates “% by mass” unless otherwise specified.

[0007] In addition to the above, the W / O / W emulsion of the present invention preferably contains the following components usually used in W / O / W type composite emulsions. Preferred as the lipophilic surfactant (emulsifier used in the primary emulsification)
HLB by Griffin is 10 or less, more preferably 7
Below, more preferably 6 or less lipophilic surfactants. A lipophilic surfactant which is incorporated into general external preparations and cosmetics and forms a W / O emulsion can be used. For example, sorbitan fatty acid ester, glycerin fatty acid ester, propylene glycol fatty acid ester,
Examples include lipophilic polyglycerin fatty acid esters, lipophilic polyoxyethylene castor oil, lipophilic polyoxyethylene hardened castor oil, lipophilic sucrose fatty acid esters, and the like, but are not particularly limited thereto. Of these, sorbitan fatty acid esters and lipophilic polyoxyethylene hydrogenated castor oil are preferred. These lipophilic surfactants may be used alone or in combination of two or more. The amount of the lipophilic surfactant varies depending on the type and the oil phase component,
Preferably 3 to 50%, more preferably 5 to 40% of the oil phase
%, Preferably 1 to 10%, more preferably 2 to 8%, based on the whole W / O / W type composite emulsion.

As the hydrophilic surfactant (emulsifier used in the secondary emulsification), a hydrophilic surfactant which is blended in general external preparations and cosmetics and forms an O / W emulsion can be used. For example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, hydrophilic polyglycerin fatty acid ester, polyoxyethylene sorbite fatty acid ester, hydrophilic polyoxyethylene castor oil, hydrophilic polyoxyethylene hardened castor oil, polyoxyethylene Sterol, hydrophilic polyethylene glycol fatty acid ester, hydrophilic polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene polymer, hydrophilic sucrose fatty acid ester, etc. But are not particularly limited to these. Of these, hydrophilic polyethylene glycol fatty acid esters and hydrophilic polyoxyethylene alkyl ethers are preferred.
These hydrophilic surfactants may be used alone or in combination of two or more. The amount of the hydrophilic surfactant varies depending on the type and the oil phase component and the amount of the lipophilic surfactant, but is preferably 0.3 to 10% based on the external water phase.
More preferably 0.5 to 8%, even more preferably 1 to 6%, W
For the whole / O / W type composite emulsion, preferably
0.3-5%, more preferably 0.5-3% is desirable. At this time, a blending amount within a range that does not solubilize the lipophilic surfactant used for forming the W / O emulsion is required, and the blending ratio of both is lipophilic surfactant / hydrophilic surfactant = 0.5
/ 1 to 20/1, preferably 0.8 / 1 to 15/1, more preferably 1/1 to 10/1.

The present invention can be used for pharmaceutical preparations and cosmetics by adding an active ingredient to the aqueous phase component. Examples of water-soluble active ingredients include humectants such as urea and glycerin, vitamins such as ascorbic acid and pantothenic acid, local anesthetics such as dibucaine hydrochloride and lidocaine hydrochloride,
Examples include antihistamines such as diphenhydramine hydrochloride and homosulfamine, and anti-inflammatory components such as guaiazulene. Different water-soluble components can be blended into the inner aqueous phase and the outer aqueous phase, respectively. The type of the active ingredient is not limited to the above, and may be appropriately selected. In addition, a base component that is usually compounded in an external preparation can be appropriately compounded as needed within a range not to impair the effects of the present invention. For example, parabens, benzoic acids, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, alkyltrimethylammonium chloride, chlorobutanol, preservatives such as phenoxyethanol, tocopherol, erythorbic acid,
Examples include antioxidants such as propyl gallate, BHT, BHA, and NDGA, and fragrances.

[0010]

EXAMPLES W / O / W type composite emulsions were prepared according to the compositions of Examples and Comparative Examples shown in Tables 1 to 4 below, and their production rates, storage stability in various temperature ranges, and obtained W were obtained.
The feeling of use of the / O / W type composite emulsion was evaluated. (Preparation method) An inner aqueous phase, an oil phase, and an outer aqueous phase were individually prepared, and each was heated and stirred at 70 ° C to 80 ° C and uniformly dissolved. Using a homomixer at a temperature of 70 ° C to 80 ° C, 40
While stirring the oil phase at 00 rpm to 5000 rpm, the internal aqueous phase was slowly added and emulsified for 5 to 10 minutes to obtain a W / O emulsion. Subsequently, the W / O emulsion was slowly added while stirring the outer aqueous phase at 500 to 1000 rpm.
The mixture was emulsified for 0 to 60 minutes to obtain a W / O / W type composite emulsion. (Production rate) The W / O / W production rate (%) is determined by mixing potassium chloride as a marker substance in the internal aqueous phase to prepare an emulsion, and then measuring the concentration of chloride ions present in the external aqueous phase by dialysis using an ion meter. I asked. A production rate of 100% is a state in which all the marker substances are encapsulated in the internal aqueous phase, and a production rate of 0% means that all of the marker substances migrate to the external aqueous phase and the O / W
This is a state in which the mold has undergone phase inversion. The production rate was evaluated according to the following five grades, and ◎ was judged to be a high production rate. (Generation rate (%): 8
5% or more: ◎, 70-85%: ○, 60-70%: △, 50-60
%: ▲, less than 50%: ×, emulsion not possible:-)

(Stability) The storage stability was evaluated by placing the prepared emulsion in a sample tube equipped with a screw cap, storing the emulsion under predetermined conditions, and observing the condition. The stability was evaluated on the following five levels, and △ ○ △ was judged to be a stable level. (Storage stability: no change: 、, slightly reduced viscosity: 、,
Decrease in viscosity: △, slight oil seepage on the surface: ▲, phase separation:
X) In addition, the evaluation of freeze-recoverability was performed by storing the emulsion at -20 ° C for 1 day, freezing it, leaving it at room temperature for 3 days, and observing the state. (Feeling of use) With respect to the W / O / W type composite emulsions of the following Examples and Comparative Examples, use tests were conducted on 20 panelists. The method is as follows: after resting for 15 minutes under constant temperature and humidity of 20 ° C./50% RH, a predetermined amount (0.5
mL) of the sample, spread it when applying, good fit to the skin, freshness after application, non-stickiness,
The five items of the comprehensive evaluation were rated on a five-point scale, with a total score of 20 people. (Evaluation criteria for each item: very good: 5
Point, good: 4 points, normal: 3 points, 2 bad points, very bad: 1 point
Point) The usability was evaluated on the following five levels, and △ ○ △ was judged to be a good usability. (Evaluation of usability score: 85 points or more: ◎, 70 ~
85 points: ○, 60-70 points: △, 50-60 points: ▲, less than 50 points:
×)

[0012]

[Table 1]

[0013]

[Table 2]

[0014]

[Table 3]

[0015]

[Table 4]

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C08J 3/03 CEP C08K 5/00 3/075 CEP C08J 3/03 CEP C08K 5/00 F term (reference) 4C076 AA18 BB31 EE30F FF16 GG45 4C083 AC022 AC072 AC122 AC242 AC352 AC402 AC442 AC482 AD211 AD311 AD312 AD341 AD352 CC01 DD34 FF05 4F070 CA02 CB01 CB04 4J002 AB00W AB05W AE00X DE026 EH037 FD0207 FD0206 FD

Claims (4)

[Claims] 1. A W / O / W type composite emulsion comprising a polysaccharide having a sulfone group and / or a carboxyl group in a molecule in an internal aqueous phase. 2. The polysaccharide is an acid mucopolysaccharide.
2. The W / O / W composite emulsion according to 1. 3. An internal water phase / oil phase containing a polysaccharide having a sulfone group and / or a carboxyl group in a molecule = 50 /
3. The W / O / W type composite emulsion according to claim 1, wherein the weight ratio is 50 to 90/10 (mass ratio). 4. A W / O emulsion comprising an inner aqueous phase and an oil phase containing a polysaccharide having a sulfone group and / or a carboxyl group in the molecule / outer aqueous phase = 30 / 70-80 / 2.
The W / O / W type composite emulsion according to any one of claims 1 to 3, wherein 0 (mass ratio).