Emulsified lotion

Abstract

To provide a new oil-in-water emulsified lotion that excels in emulsion stability or the like and includes sulfated polysaccharides or salts thereof.SOLUTION: An oil-in-water emulsified lotion according to one embodiment of the present invention includes sulfated polysaccharides or salts thereof (particularly, heparinoids), and myristyl alcohol or oleyl alcohol. The inventive oil-in-water emulsified lotion is equivalent to or better than the conventional products in at least viscosity and emulsion particle diameter.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an oil-in-water emulsion lotion preparation containing a sulfated polysaccharide as an active ingredient, which is useful as a medicine, quasi-drug, etc. [Background technology]

[0002] Lotions are generally liquid topical preparations that are applied to the skin and are made by dissolving or finely and evenly dispersing active ingredients in an aqueous liquid. Depending on the state, they are classified as suspension lotions, emulsion lotions, or solution lotions. Emulsion lotions are also known as milky lotions, and oil-in-water lotions are preferred due to their pleasant feel when used. Oil-in-water emulsion lotions are emulsion systems similar to oil-in-water emulsion ointments (creams), and therefore basically consist of oily components, aqueous components, and surfactants (emulsifiers), but even though they are the same emulsion system, it is difficult to stabilize the emulsion because the external phase (aqueous phase) is not solidified. A known solution to this problem is to increase the viscosity of the external phase, and a commonly used method is to add water-soluble polymers such as carboxyvinyl polymers and hydroxypropyl cellulose as thickeners.

[0003] Sulfated polysaccharides, especially heparinoids, are used as blood circulation promoters and skin moisturizers in the form of creams (O / W type, W / O type), lotions, foams, and sprays. Patent Document 1 discloses a skin moisturizer containing a polysulfate of chondroitin sulfate as an active ingredient as a preparation containing a salt of sulfated polysaccharide. In this patent document, the formulations of the skin moisturizer include cleansers, creams, skin lotions, lotions, and lipsticks. According to the current classification of formulations, lotions include plant juice lotions, alkaline lotions, astringent lotions, hand lotions, milky lotions, foundation lotions, and cleansing lotions, which are classified as lotions, but the majority of lotions are solution lotions that do not require emulsion stabilization technology in oil-in-water emulsion lotions. In addition, there is no particular mention of the stability of milky lotions, i.e., emulsion lotions.

[0004] It is possible to stabilize an emulsion-type lotion containing a sulfated polysaccharide or a salt thereof, such as a polysulfate of chondroitin sulfate, by the above-mentioned emulsion stabilization method, i.e., by adding a water-soluble polymer; however, the sulfated polysaccharide or its salt tends to inhibit the thickening effect of the water-soluble polymer, and it is difficult to stabilize the emulsion by such a method in the case of an oil-in-water emulsion lotion containing a sulfated polysaccharide or its salt.

[0005] In general, emulsion lotions contain less oily ingredients compared to other topical preparations (oleaginous ointments and emulsion ointments), and therefore have an excellent feel when used and the advantage of leaving less residual sensation on the skin. However, they have problems with sustaining efficacy due to their poor skin coverage.

[0006] In order to address the above-mentioned problems associated with oil-in-water emulsion lotions containing sulfated polysaccharides or their salts, an invention has been disclosed in which an emulsion stabilizer such as reduced lanolin is incorporated (Patent Document 2). According to this patent document, it is possible to obtain an oil-in-water emulsion lotion that ensures emulsion stability and has skin moisturizing effects as excellent as those of emulsion ointments (creams) by incorporating an emulsion stabilizer such as reduced lanolin. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Publication No. 112708 / 1983 [Patent Document 2] Japanese Patent Application Publication No. 11-180821 Summary of the Invention [Problem to be solved by the invention]

[0008] The problem of emulsion stability in the above-mentioned oil-in-water emulsion lotion is a problem generally required for emulsion lotions. Considering the possibility of various circumstances, including the future, such as combinations with other ingredients and economical efficiency, it is socially preferable that a variety of solutions are provided, not just one.

[0009] An object of the present invention is to provide a novel oil-in-water emulsion lotion preparation containing a sulfated polysaccharide or a salt thereof, which has excellent emulsion stability and the like. [Means for solving the problem]

[0010] As a result of extensive research, the present inventors have found that the above problems can be solved by adding a certain higher aliphatic alcohol as an emulsion stabilizer, and have thus completed the present invention.

[0011] The present invention can include, for example, the following. [1] An oil-in-water emulsion lotion comprising a sulfated polysaccharide or a salt thereof, and myristyl alcohol or oleyl alcohol. [2] The oil-in-water emulsion lotion according to the above-mentioned [1], wherein the sulfated polysaccharide is a polysulfide of mucopolysaccharide. [3] The oil-in-water emulsion lotion according to the above item [2], wherein the polysulfide of mucopolysaccharide is a heparinoid. [4] The oil-in-water emulsion lotion according to any one of the above [1] to [3], further comprising one or more components selected from the group consisting of a surfactant, a hydrocarbon base, a moisturizer, a thickener, a pH adjuster, a stabilizer and a preservative. [5] The oil-in-water emulsion lotion according to any one of the above [1] to [3], further comprising one or more components selected from the group consisting of polyoxyethylene alkyl ethers, glycerol fatty acid esters, hydrocarbons, polyols, alkanolamines, carboxyvinyl polymers, and paraoxybenzoic acid esters. [6] The oil-in-water emulsion lotion according to any one of the above [1] to [3], further comprising one or more components selected from the group consisting of polyoxyethylene cetyl ether, glyceryl monostearate, white petrolatum, squalane, glycerin, alkanolamines, carboxyvinyl polymers, and paraoxybenzoic acid esters. [7] An oil-in-water emulsion lotion comprising a heparinoid, cetanol, myristyl alcohol, polyoxyethylene cetyl ether, glyceryl monostearate, white petrolatum, squalane, glycerin, diisopropanolamine, carboxyvinyl polymer, and paraoxybenzoic acid ester. Effect of the Invention

[0012] The oil-in-water emulsion lotion containing a sulfated polysaccharide or a salt thereof, particularly a heparinoid, according to the present invention is at least as good as or better than conventional ones in terms of viscosity and emulsion particle size. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] The present invention will be described in detail below. The oil-in-water emulsion lotion according to the present invention (hereinafter referred to as "the lotion of the present invention") is characterized by containing a sulfated polysaccharide or a salt thereof, and myristyl alcohol or oleyl alcohol. The sulfated polysaccharides of the present invention include sulfated polysaccharides in which the main constituent monosaccharides are, for example, D-glucosamine, D-galactosamine, D-glucuronic acid, L-iduronic acid, D-glucose, D-galactose, or D-xylose, and a polymer having one or more of these monosaccharides as repeating units is sulfated.

[0014] Furthermore, the sulfated polysaccharides according to the present invention include polysaccharides which naturally contain sulfate groups, and polysaccharides which naturally contain sulfate groups and which are obtained by further artificially sulfating them.

[0015] Furthermore, the sulfated polysaccharides according to the present invention include heparin-like substances, which are polymeric substances having anticoagulant properties, and heparin-like substances also include polymeric substances not composed of sugars that have similar properties.

[0016] Specific examples of sulfated polysaccharides according to the present invention include sulfates of mucopolysaccharides such as heparin, chondroitin, hyaluronic acid, etc.; mucopolysaccharides that already contain sulfate groups in nature, such as chondroitin sulfate D and chondroitin sulfate E, which are called chondroitin polysulfates, and keratan polysulfate; polysulfates obtained by further sulfate-adding such polysaccharides that naturally contain sulfate groups; sulfates of chitin; sulfates of starch, cellulose, guar gum, gum arabic, konjac mannan, agar agarose, amylopectin, etc.

[0017] Among these sulfated polysaccharides, in the present invention, sulfated mucopolysaccharides (including mucopolysaccharides that already have sulfate groups in nature and further sulfated mucopolysaccharides) are preferred, and polysulfate esters of chondroitin sulfate are particularly preferred.

[0018] As described above, the sulfated polysaccharide according to the present invention includes a heparinoid. The heparinoid refers to a heparinoid defined in the Japanese Pharmacopoeia. The heparinoid defined in the Japanese Pharmacopoeia has a polysulfate ester of chondroitin sulfate as a main component. In this specification, unless otherwise specified, the term "heparinoid" simply refers to a heparinoid defined in the Japanese Pharmacopoeia.

[0019] Examples of salts of sulfated polysaccharides include alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as calcium and magnesium, and also include multiple salts of these.

[0020] The number of sulfate groups contained in the sulfated polysaccharide is an average of 0.55 to 5 per repeating saccharide unit, preferably an average of 0.7 to 2. When the polysaccharide is a mucopolysaccharide that already has sulfate groups before sulfation, such as chondroitin polysulfate, the number of sulfate groups contained in the sulfated polysaccharide is an average of 0.55 to 5 per repeating saccharide unit, preferably an average of 0.6 to 2.9, more preferably an average of 0.7 to 2.

[0021] The average molecular weight of the sulfated polysaccharide or a salt thereof is suitably about 1,000 to 10,000,000, preferably about 5,000 to 1,000,000, and more preferably about 10,000 to 100,000.

[0022] In the lotion of the present invention, these sulfated polysaccharides or salts thereof may be used alone or in any combination of two or more kinds.

[0023] The sulfation reaction for introducing sulfate groups into the polysaccharides described above is carried out, for example, as follows.

[0024] First, a suitable ice-cooled solvent is prepared, and a sulfating agent is added thereto to obtain a mixture. The raw material polysaccharide is added to the mixture, and the mixture is reacted at 0° C. to 100° C. for 1 to 10 hours to carry out sulfation.

[0025] The amount of solvent used may vary depending on the type of raw polysaccharide used, the desired sulfated polysaccharide, etc., but is suitably 10 to 30 mL per 1 g of raw polysaccharide. The amount of sulfating agent used is also appropriately selected depending on the type of raw polysaccharide used and the desired sulfated polysaccharide, but for example, 2 to 6 g can be used per 1 g of raw polysaccharide.

[0026] The solvent used is appropriately selected depending on the type of raw material polysaccharide used and the desired sulfated polysaccharide, and is not particularly limited. Examples of the solvent include pyridine, N,N-dimethylformamide, and N,N-dialkylacrylamide.

[0027] Similarly, the sulfating agent is not particularly limited as long as it can produce the desired sulfated polysaccharide, and examples of the sulfating agent include chlorosulfonic acid and triethylamine-sulfur trioxide complex salt.

[0028] The content of the sulfated polysaccharide or a salt thereof in the lotion of the present invention is not particularly limited as long as the effects of the present invention are not impaired, but is suitably within the range of 0.05% by weight to 1.0% by weight, preferably 0.1% by weight to 0.5% by weight, and more preferably 0.2% by weight to 0.4% by weight, based on the total amount of the lotion of the present invention.

[0029] The lotion of the present invention contains one or more higher aliphatic alcohols such as myristyl alcohol and oleyl alcohol, which can be considered as components that stabilize the lotion of the present invention or components that assist in stabilization (emulsion stabilizers or emulsification aids).The present invention does not exclude the lotion of the present invention from containing other emulsion stabilizers or emulsification aids, such as reduced lanolin, but reduced lanolin is basically not required. In addition, reduced lanolin is also called hydrogenated lanolin, and is obtained by hydrogenating (reducing) lanolin, and is known to be composed of esters, hydrocarbons, and alcohols. During reduction, esters and fatty acids constituting lanolin are also reduced to alcohols, so reduced lanolin is a mixture containing higher alcohols constituting lanolin or alcohols obtained by hydrogenating them, alcohols obtained by hydrogenating esters constituting lanolin, and alcohols obtained by hydrogenating fatty acids constituting lanolin. In the present invention, containing reduced lanolin means containing reduced lanolin as the whole mixture, not only some of the constituent components, unless otherwise specified. The lotion of the present invention may contain reduced lanolin, or may contain one or more individual alcohols. Reduced lanolin enhances emulsion stability, but it is known that it is very difficult to separate and identify the complex and enormous amount of contained components. The lotion of the present invention has good effects on emulsion particle size, viscosity, etc., even if it does not contain reduced lanolin.

[0030] The content of myristyl alcohol and / or oleyl alcohol in the lotion of the present invention is not particularly limited as long as it does not impair the effects of the present invention, but is appropriately within the range of 0.05% by weight to 15.0% by weight, preferably 0.1% by weight to 5.0% by weight, and more preferably 0.3% by weight to 1.5% by weight, based on the total amount of the lotion of the present invention.

[0031] In the present invention, the blending ratio (by weight) of the sulfated polysaccharide or a salt thereof to myristyl alcohol and / or oleyl alcohol is suitably within the range of 20:1 to 1:300, preferably within the range of 10:1 to 1:30, and more preferably within the range of 1:1 to 1:5.

[0032] When the lotion of the present invention contains cetanol, the content of the cetanol is not particularly limited as long as it does not impair the effects of the present invention, but is suitably within the range of 0.01% by weight to 5.0% by weight, preferably within the range of 0.1% by weight to 2.0% by weight, and more preferably within the range of 0.3% by weight to 1.0% by weight, based on the total amount of the lotion of the present invention.

[0033] The lotion of the present invention may contain one or more other components that are generally contained in order to form an oil-in-water emulsion lotion, such as a surfactant, a hydrocarbon base, a moisturizing agent, a thickener, a pH regulator, a stabilizer, or a preservative. In addition, since the present invention relates to an oil-in-water emulsion lotion, it contains an appropriate amount of water (e.g., purified water, distilled water, tap water, RO water).

[0034] Examples of the surfactant include cationic surfactants, anionic surfactants, amphoteric surfactants, and nonionic surfactants. These may be used alone or in any combination of two or more kinds.

[0035] Specific examples of the cationic surfactant that can be used in the present invention include cetyltrimethylammonium chloride, lauryldimethylbenzylammonium chloride, tetrabutylammonium chloride, and dioctadecyldimethylammonium chloride.

[0036] Specific examples of the anionic surfactant that can be used in the present invention include sodium alkylbenzene sulfonate, sodium dodecyl sulfate, sodium coconut alcohol ethoxy sulfate, and sodium α-olefin sulfonate.

[0037] Specific examples of the nonionic surfactant that can be used in the present invention include polyoxyethylene alkyl ethers, polyoxyethylene alkylphenol ethers, sorbitan fatty acid esters, glycerin fatty acid esters, and sucrose fatty acid esters.

[0038] Specific examples of the amphoteric surfactant that can be used in the present invention include N-alkyl-N,N-dimethylammonium betaine, imidazoline-type amphoteric surfactants, and the like.

[0039] Of the above surfactants, for example, polyoxyethylene alkyl ethers (specific examples: polyoxyethylene lauryl ether, polyoxyethylene behenyl ether, polyoxyethylene cetyl ether) and glycerin fatty acid esters (specific examples: glycerin monopalmitate, glycerin monostearate, glycerin monooleate, glycerin monolinoleate) are preferred in the present invention.

[0040] The content of the surfactant is not particularly limited as long as it functions as an emulsifier, but it is appropriate that the content is within the range of 0.2% by weight to 5% by weight based on the total amount of the lotion of the present invention. Furthermore, since the lotion of the present invention is expected to be used as a medicine, cosmetic, etc., it is preferable that the surfactant contains as small an amount as possible of nonionic surfactants as the main component of these surfactants.

[0041] Specific examples of the hydrocarbon base that may be contained in the lotion of the present invention include liquid paraffin, squalane, synthetic squalane, white petrolatum, ceresin wax, solid paraffin, microstearate wax, etc. Among these, squalane and white petrolatum are preferred. The hydrocarbon base may be used alone or in combination of any two or more kinds.

[0042] The content of the hydrocarbon base is not particularly limited as long as it does not impair the effects of the present invention, but it is appropriate that the content is within the range of 1% by weight to 10% by weight, for example, relative to the total amount of the lotion of the present invention.

[0043] Specific examples of moisturizers that may be contained in the lotion of the present invention include polyols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, hexylene glycol, diethylene glycol, glycerin, diglycerin, glucose, maltose, xylitol, and sorbitol; sodium pyrrolidone carboxylate; and sodium lactate. Of these, glycerin and 1,3-butylene glycol are preferred. The moisturizing agent may be used alone or in combination of any two or more kinds.

[0044] The content of the moisturizer is not particularly limited as long as it does not impair the effects of the present invention, but it is appropriate that the content is within the range of 5% by weight to 30% by weight, for example, based on the total amount of the lotion of the present invention.

[0045] Specific examples of thickeners that can be contained in the lotion of the present invention include carboxyvinyl polymers, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, carrageenan, xanthan gum, gelatin, etc. Among these, carboxyvinyl polymers are preferred. The thickener may be used alone or in combination of any two or more kinds.

[0046] The content of the thickener is not particularly limited as long as it does not impair the effects of the present invention, but it is appropriate that the content is within the range of 0.05% by weight to 1% by weight, for example, based on the total amount of the lotion of the present invention.

[0047] Examples of pH adjusters that may be contained in the lotion of the present invention include alcohol amines such as diisopropanolamine, triisopropanolamine, and triethanolamine; potassium hydroxide, sodium hydroxide, sodium citrate, phosphoric acid, tartaric acid, dl-malic acid, glacial acetic acid, etc. Among these, alcohol amines are preferred, and diisopropanolamine is more preferred. The pH adjusting agent may be used alone or in combination of any two or more kinds.

[0048] The content of the pH adjuster is not particularly limited as long as it does not impair the effects of the present invention, but it is appropriate that the content is within the range of 0.05% by weight to 1% by weight, for example, based on the total amount of the lotion of the present invention.

[0049] Examples of stabilizers or preservatives or antiseptics (hereinafter referred to as "stabilizers, etc.") that can be contained in the lotion of the present invention include parabens (paraoxybenzoic acid esters) such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate; phenoxyethanol, and 1,3-butylene glycol. The stabilizer or preservative may be used alone or in combination of any two or more kinds.

[0050] The content of the stabilizer etc. is not particularly limited as long as it does not impair the effects of the present invention, but it is appropriate that it is within the range of 0.05% by weight to 1% by weight, for example, based on the total amount of the lotion of the present invention.

[0051] The lotion of the present invention may also contain other ingredients, such as oils and fats, waxes, fatty acids, esters, etc., which are used in the fields of pharmaceuticals, cosmetics, etc. These other ingredients may be blended in appropriate combinations depending on the purpose of use.

[0052] Specific examples of the oils and fats that can be contained in the lotion of the present invention include olive oil, soybean oil, camellia oil, palm oil, castor oil, and the like.

[0053] Specific examples of waxes that can be contained in the lotion of the present invention include beeswax, carnauba wax, Japan wax, liquid lanolin, hard lanolin, and the like.

[0054] Specific examples of fatty acids that can be contained in the lotion of the present invention include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and the like.

[0055] Specific examples of esters that can be contained in the lotion of the present invention include cetyl lactate, isopropyl myristate, octyldodecyl myristate, and the like.

[0056] The content of the above other ingredients is not particularly limited and can be appropriately changed depending on the application, desired feel during use, etc., but in consideration of the feel on the skin, it is appropriate that the content is within the range of 1.0 to 30% by weight or less based on the total amount of the lotion of the present invention.

[0057] Furthermore, the lotion of the present invention may contain, if necessary, ingredients used in cosmetics and pharmaceuticals other than those mentioned above, within the scope of not impairing the effects of the present invention. For example, sequestering agents, ultraviolet absorbers, medicines, dispersants, etc. may be mentioned. EXAMPLES

[0058] The present invention will be described in detail below with reference to examples and test examples (Examples, etc.), but the present invention is not limited to the embodiments of the following Examples, etc.

[0059] [Reference Examples and Examples 1 to 5] Each oil-in-water emulsion lotion was prepared by a conventional method according to the formulation shown in Table 1. The reference example is an embodiment of the invention described in Patent Document 2.

[0060] [Table 1]

[0061] [Test Example 1] For Reference Example and Examples 1 to 5, the presence or absence of phase separation, viscosity, emulsion particle size, and properties were observed after 4 weeks at 50°C. The presence or absence of phase separation was observed visually, and the viscosity was measured with a modular compact rheometer (MCR302, manufactured by Anton Paar Japan). The emulsion particle size was measured by placing a small amount of each formulation on a slide glass, covering it with a cover glass, and observing it under a microscope (objective lens: 40x or 100x, eyepiece lens: 10x). Evaluation was performed according to the following criteria.

[0062] (Evaluation Criteria) A: Only emulsified particles of 1 to 2 μm B: Emulsion particles of 1 to several μm are mixed B': Mainly emulsified particles of 1 to several μm, including emulsified particles of 10 or so μm C: Emulsion particles of 1 to several tens of μm are mixed C': Mainly emulsified particles of 1 to 10 μm, including emulsified particles of several tens of μm D: Emulsion particles of 1 to several tens of μm are mixed E:Other The results are shown in Table 2.

[0063] [Table 2]

[0064] As is clear from the results shown in Table 2, Examples 1 to 5 of the lotion of the present invention were equal to or greater than the Reference Example in terms of viscosity and emulsion particle size. When applied to the skin, white residue and clumping were further reduced, and a high-quality lotion was obtained.

[0065] [Comparative Example] Each oil-in-water emulsion lotion was prepared in a conventional manner according to the formulation shown in Table 3, replacing the oleyl alcohol and myristyl alcohol in the above examples with cetanol or stearyl alcohol.

[0066] [Table 3]

[0067] [Test Example 2] For each of the comparative examples, the presence or absence of phase separation, viscosity, emulsion particle size, and properties were observed after 4 weeks at 50° C. in the same manner as in the above-mentioned examples, etc. The results are shown in Table 4.

[0068] [Table 4] As is clear from the results shown in Table 4, in the case of the comparative examples which did not contain reduced lanolin, oleyl alcohol, and myristyl alcohol, but contained cetanol or stearyl alcohol instead, the emulsion particle size and viscosity tended to increase and were inferior to the reference examples.

[0069] [Examples 6 to 11] According to the formulations shown in Table 5, each oil-in-water emulsion lotion was prepared by a conventional method.

[0070] [Table 5]

[0071] Examples 6 to 11 also had excellent viscosity and emulsion stability. When applied to the skin, white residue and clumping were further reduced, and high-quality lotions were obtained. [Industrial Applicability]

[0072] As is clear from the results of the above test examples, the lotion of the present invention is excellent in emulsion stability and the like, and the present invention is useful, for example, in the fields of pharmaceuticals and cosmetics.

Claims

1. 1. An oil-in-water emulsion lotion comprising a sulfated polysaccharide or a salt thereof, and myristyl alcohol or oleyl alcohol.

2. 2. The oil-in-water emulsion lotion according to claim 1, wherein the sulfated polysaccharide is a polysulfide of mucopolysaccharide.

3. 3. The oil-in-water emulsion lotion according to claim 2, wherein the polysulfide of mucopolysaccharide is a heparinoid.

4. The oil-in-water emulsion lotion according to any one of claims 1 to 3, further comprising one or more components selected from the group consisting of a surfactant, a hydrocarbon base, a moisturizer, a thickener, a pH adjuster, a stabilizer and a preservative.

5. The oil-in-water emulsion lotion according to any one of claims 1 to 3, further comprising one or more components selected from the group consisting of polyoxyethylene alkyl ethers, glycerin fatty acid esters, hydrocarbons, polyols, alkanolamines, carboxyvinyl polymers, and paraoxybenzoic acid esters.

6. The oil-in-water emulsion lotion according to any one of claims 1 to 3, further comprising one or more components selected from the group consisting of polyoxyethylene cetyl ether, glyceryl monostearate, white petrolatum, squalane, glycerin, alkanolamines, carboxyvinyl polymers, and paraoxybenzoic acid esters.

7. An oil-in-water emulsion lotion comprising heparinoids, cetanol, myristyl alcohol, polyoxyethylene cetyl ether, glycerin monostearate, white petrolatum, squalane, glycerin, diisopropanolamine, carboxyvinyl polymer, and paraoxybenzoic acid ester.

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