JP6522908B2 - Composition for external use - Google Patents

Description

  The present invention relates to an external use composition having excellent formulation stability in which the formation of precipitates with time is suppressed while containing two or more types of ceramide of ceramides 1 to 3 and water.

  It is known that when the barrier function or moisturizing function of the stratum corneum decreases due to various environmental factors such as dryness and ultraviolet rays, aging of the skin with aging, and atopic lesions, skin symptoms such as rough skin and dry skin occur. In order to keep the skin healthy, it is important to keep the barrier function and the moisturizing function of the stratum corneum appropriate.

  The stratum corneum is mainly composed of stratum corneum cells and intercellular lipids forming a lamellar structure, and the lamellar structure of stratum corneum intercellular lipids plays an important role in the barrier function and the moisturizing function. . In addition, about 50% of the stratum corneum intercellular lipid is composed of ceramide, and it is known that when the content of ceramide in the stratum corneum decreases, the barrier function and the moisturizing function decrease. Then, the external composition which mix | blended ceramide is conventionally developed in order to maintain the function of a stratum corneum by supplementing the ceramide in a stratum corneum. However, ceramide has a characteristic property of high crystallinity, is difficult to be dissolved in the base material (particularly water) of the composition for external use, and has a disadvantage that it precipitates during storage even if it is once dissolved.

  Heretofore, various investigations have been made on formulation techniques for suppressing the precipitation of ceramide. For example, Patent Document 1 discloses that the precipitation with time of ceramide can be suppressed by blending and emulsifying an alkyloyl lactic acid ester with ceramides. Further, in Patent Document 2, the temporal precipitation of ceramide is suppressed by blending together with ceramide an alkyloyl lactic acid and / or a salt thereof, and glycerin and / or a polyglycerin fatty acid ester having a degree of polymerization of 2 or more. What can be done is disclosed. Furthermore, Patent Document 3 contains a high concentration of ceramide (1.0 to 5.0% by weight) by blending a long-chain fatty acid having 12 to 24 carbon atoms, a nonionic surfactant, and water together with ceramide. It is disclosed that a transparent, highly stable aqueous transparent composition can be obtained even when containing

JP 2000-256188 A JP, 2001-199872, A JP 2001-316217 A

  It is known that 11 types of ceramides (ceramides 1 to 5, 6-1, 6-2, and 7 to 10) exist in the stratum corneum, and the function of each type of ceramide is also different. It is done. In addition, when two or more types of ceramides are combined and formulated, depending on the combination mode, if the solubility of ceramides may increase and it may be difficult to precipitate, conversely, the solubility of ceramides may decrease to further precipitate more. It is known that it may be easy to occur.

  On the other hand, ceramide 1 is mainly responsible for the barrier function, ceramides 2 and 3 mainly for the moisturizing function, and ceramides 1 to 3 are known to play an especially important role in the stratum corneum . Therefore, in the externally applied composition for the purpose of replenishing ceramide to the stratum corneum, it is effective to blend two or more of ceramides 1 to 3. However, it has been found that when two or more of ceramides 1 to 3 are combined and formulated, the solubility of ceramide is further reduced, the precipitation is further facilitated, and the formulation stability is impaired (described later) Reference Examples 1 to 3). Therefore, even in the formulation techniques disclosed in Patent Documents 1 to 3, when two or more of ceramides 1 to 3 are combined, it is not satisfactory in terms of suppression of precipitation of ceramide.

  Therefore, an object of the present invention is to provide an external composition having excellent formulation stability, in which the formation of precipitates with time is suppressed while containing two or more of ceramides of ceramides 1 to 3 and water. It is to be.

The inventors of the present invention conducted intensive studies to solve the above problems, and found that higher fatty acids, nonionic surfactants, polyhydric alcohols, and citric acid, together with two or more of ceramides of ceramides 1 to 3 and water. By combining and combining an acid and / or an alkali metal salt thereof, it has been found that the formation of precipitates with time can be suppressed, and an external use composition having excellent formulation stability can be obtained. The present invention has been completed by further studies based on such findings.
That is, the present invention provides the invention of the aspects listed below.
Item 1. (A) at least two ceramides selected from the group consisting of ceramide 1, ceramide 2 and ceramide 3, (B) higher fatty acid, (C) nonionic surfactant, (D) polyhydric alcohol, (E) An externally applied composition comprising citric acid and / or an alkali metal salt thereof, and (F) water.
Item 2. The composition for external use according to item 1, wherein the component (A) is a combination of ceramide 2 and ceramide 1 and / or ceramide 3.
Item 3. The composition for external use according to item 1 or 2, wherein the component (C) is polyoxyethylene hydrogenated castor oil.
Item 4. The composition for external use according to any one of Items 1 to 3, wherein the component (E) is a sodium salt of citric acid.
Item 5. The composition for external use according to any one of Items 1 to 4, wherein the total amount of the component (A) is 0.000001 to 0.05% by weight.
Item 6. The composition for external use according to any one of Items 1 to 5, wherein the component (B) is contained in an amount of 0.001 to 0.1% by weight.
Item 7. The composition for external use according to any one of Items 1 to 6, wherein the component (C) is contained in 0.01 to 0.5% by weight.
Item 8. The composition for external use according to any one of Items 2 to 7, wherein 0.00001 to 10000 parts by weight of Ceramide 1 and / or 0.00001 to 10000 parts by weight of Ceramide 3 are contained per 1 part by weight of Ceramide 2.
Item 9. The composition for external use according to any one of Items 1 to 8, which is a cosmetic.
Item 10. The composition for external use according to any one of Items 1 to 9, which is a lotion.

  According to the composition for external use of the present invention, although containing two or more of ceramides 1 to 3 and water, the formation of precipitates with time can be suppressed, and excellent formulation stability can be provided. . Further, in the composition for external use of the present invention, even if two or more of ceramides 1 to 3 and water are contained, the solubility of these ceramides is improved, and these ceramides are preferably 0.01 to 0. Since the composition can be formulated at a high content of 05% by weight, an external composition that can more effectively enjoy the beneficial effects (moisturizing, rough skin improvement, elimination of sensitive skin, prevention of skin aging, etc.) based on these ceramides. It also becomes possible to provide things.

  The composition for external use of the present invention comprises (A) at least two ceramides selected from the group consisting of ceramide 1, ceramide 2 and ceramide 3, (B) higher fatty acid, (C) nonionic surfactant, (D) A) a polyhydric alcohol, (E) citric acid and / or an alkali metal salt thereof, and (F) water. Hereinafter, the composition for external use of the present invention will be described in detail.

(A) Ceramide The composition for external use of the present invention contains two or more kinds of ceramides from ceramide 1, ceramide 2 and ceramide 3. In the composition for external use according to the present invention, even when two or more of ceramides 1 to 3 are used in combination to formulate with water, temporally precipitates by integrally containing the components (B) to (E) described later. It becomes possible to suppress the generation of objects.

(Ceramide 1)
Specific examples of ceramide 1 used in the present invention include N- (ω-acyloxy-acyl) phytosphingosine and N- (ω-acyloxy-acyl) sphingosine.

  In the acyloxyacyl group constituting ceramide 1, the carbon number of the acyl group on the side linked to phytosphingosine or sphingosine via an amide bond (hereinafter also referred to as "acyl group on the amide bond side") is not particularly limited. For example, about 20 to 38, preferably 20 to 34, more preferably 24 to 30, still more preferably 26 to 27, and particularly preferably 27. The acyl group on the amide bond side may be either linear or branched, and may be saturated or unsaturated, but is preferably linear and saturated.

  In the acyloxyacyl group constituting ceramide 1, the carbon number of the acyl group linked to the acyl group on the amide bond side via an ester bond (hereinafter also referred to as "acyl group on the ester bond") is Although not particularly limited, for example, about 12 to 38, preferably 14 to 30, more preferably 16 to 28, more preferably 16 to 20, and particularly preferably 18 are mentioned. The acyl group on the ester bond side may be either linear or branched, and may be saturated or unsaturated, but is preferably linear and saturated. Furthermore, the acyl group on the ester bond side may contain a hydroxyl group.

  These ceramides 1 may be used alone or in combination of two or more.

  Among ceramides 1, N- (ω-acyloxy-acyl) phytosphingosine is preferably mentioned.

(Ceramide 2)
Specific examples of ceramide 2 used in the present invention include N-acyl dihydrosphingosine and N-acyl sphingosine.

  The carbon number of the acyl group constituting the ceramide 2 is not particularly limited, but, for example, about 12 to 38, preferably 14 to 30, more preferably 16 to 28, more preferably 16 to 24, particularly preferably 18 Be

  The acyl group constituting the ceramide 2 may be either linear or branched, and may be either saturated or unsaturated, but is preferably linear and saturated. Moreover, although the acyl group which comprises ceramide 2 may contain a hydroxyl group, it is preferable that it is an acyl group which does not contain a hydroxyl group.

  These ceramides 2 may be used alone or in combination of two or more.

  Among ceramides 2, preferably N-acyl dihydrosphingosine is mentioned.

(Ceramide 3)
Specifically as ceramide 3 used by this invention, N-acyl phytosphingosine is mentioned.

  The carbon number of the acyl group constituting the ceramide 3 is not particularly limited, but for example, about 12 to 38, preferably 14 to 30, more preferably 16 to 28, more preferably 16 to 24, particularly preferably 18 Be

  The acyl group constituting the ceramide 3 may be linear or branched, and may be saturated or unsaturated, but is preferably linear or saturated. Moreover, although the acyl group which comprises ceramide 3 may contain a hydroxyl group, it is preferable that it is an acyl group which does not contain a hydroxyl group.

(A combination mode of ceramides 1 to 3)
In the composition for external use of the present invention, two or more of ceramides 1 to 3 are used in combination. In the composition for external use of the present invention, the combination mode of ceramides 1 to 3 is not particularly limited, and a combination of ceramide 1 and ceramide 2, a combination of ceramide 1 and ceramide 3, a combination of ceramide 2 and ceramide 3, ceramide 1 and ceramide 3 Any combination of ceramide 2 and ceramide 3 may be used. In particular, in the prior art, when ceramide 2 is combined with ceramide 1 and / or 3, especially when ceramide 1 is combined with ceramide 2 and ceramide 3, the solubility of ceramide is further reduced, Although there is a problem that the formation of precipitates with time becomes remarkable, in the present invention, such problems of the prior art can be solved, and the generation of precipitates with time can be effectively suppressed. It has become. In view of the effects of the present invention, the combination of ceramides 1 to 3 is preferably a combination of ceramide 2 and ceramide 1 and / or 3 and more preferably a combination of ceramide 1 to ceramide 2 and ceramide 3 It can be mentioned.

(Content and ratio of ceramides 1 to 3)
In the composition for external use of the present invention, the content of ceramides 1 to 3 may be appropriately set according to the formulation form of the composition for external use, etc. For example, the total amount of ceramides 1 to 3 is 0.000001 to 0 There may be .05% by weight. In general, when the content of ceramides 1 to 3 is high, formation of precipitates with time tends to be remarkable in the composition for external use, but in the composition for external use of the present invention, ceramide 1 Even when .about.3 is contained at a high content of 0.01% by weight or more, the formation of precipitates with time can be effectively suppressed. In view of such effects of the present invention, the content of ceramides 1 to 3 in the composition for external use of the present invention is preferably 0.00001 to 0.05% by weight, more preferably 0.01 to 0.05% by weight. % Is listed.

  More specifically, when ceramide 1 is contained, the lower limit of the content of ceramide 1 in the composition for external use of the present invention is 0.0000001 wt%, more preferably 0.000001 wt%, still more preferably 0. 00001 weight% is mentioned. The upper limit of the content of ceramide 1 is 0.03% by weight, preferably 0.01% by weight, and more preferably 0.0001% by weight. When ceramide 2 is contained, the lower limit of the content of ceramide 2 in the composition for external use of the present invention is 0.0000005% by weight, more preferably 0.0001% by weight, more preferably 0.001% by weight, and further preferably Is 0.01% by weight. Moreover, as an upper limit of content of ceramide 2, 0.049 weight%, Preferably 0.03 weight% is mentioned. When ceramide 3 is contained, the lower limit of the content of ceramide 3 in the composition for external use of the present invention is 0.0000001 wt%, preferably 0.000001 wt%, more preferably 0.00001 wt%. Moreover, as an upper limit of content of ceramide 3, 0.04 weight%, Preferably 0.03 weight% is mentioned.

Further, in the composition for external use of the present invention, the ratio of each ceramide is not particularly limited, and for example, the range shown below can be mentioned.
When ceramide 1 and ceramide 2 are combined: 0.00001 to 10000 parts by weight, preferably 0.00001 to 100 parts by weight, more preferably 0.00001 to 1 parts by weight of ceramide 1 per 1 part by weight of ceramide 2.
When ceramide 1 and ceramide 3 are combined: 0.00001 to 10000 parts by weight, preferably 0.0001 to 10000 parts by weight, more preferably 0.1 to 1000 parts by weight of ceramide 3 per 1 part by weight of ceramide 1.
When ceramide 2 and ceramide 3 are combined: 0.00001 to 10000 parts by weight, preferably 0.00001 to 1000 parts by weight, more preferably 0.00001 to 100 parts by weight of ceramide 3 per 1 part by weight of ceramide 2.
When combining ceramide 1 with ceramide 2 with ceramide 3: 0.00001 to 10000 parts by weight, preferably 0.00001 to 100 parts by weight, more preferably 0.00001 to 1 part by weight of ceramide 1 per 1 part by weight of ceramide 2 Part; 0.00001 to 10000 parts by weight, preferably 0.00001 to 1000 parts by weight, more preferably 0.00001 to 100 parts by weight of ceramide 3.

(B) Higher Fatty Acid The composition for external use of the present invention contains higher fatty acid. In the composition for external use of the present invention, the higher fatty acid contributes to the suppression of the formation of precipitates with time together with the components (C) to (E) described later.

  The carbon number of the higher fatty acid used in the present invention is not particularly limited, and, for example, 16 to 20 can be mentioned. From the viewpoint of further improving the solubility of ceramide and the inhibitory effect on the precipitation formation with time, the number of carbon atoms of the higher fatty acid is preferably 18, preferably.

  Further, the higher fatty acid used in the present invention may be either linear or branched, and may be either saturated fatty acid or unsaturated fatty acid, but the solubility of ceramide and temporally It is preferable that it is a branched or unsaturated higher fatty acid from the viewpoint of further improving the suppression effect of precipitation formation.

  Specific examples of the higher fatty acids used in the present invention include lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linoleic acid, arachidonic acid, behenic acid and eicosapentaene. Examples include acids and docosahexaenoic acid.

  In the composition for external use of the present invention, one kind of higher fatty acids may be selected and used alone, or two or more kinds may be used in combination.

  The higher fatty acid used in the present invention is preferably an unsaturated fatty acid having 16 to 20 carbon atoms or a branched fatty acid, from the viewpoint of further improving the solubility of ceramide and the suppressing effect on precipitation formation with time. And C 18 unsaturated fatty acid or branched fatty acid, more preferably isostearic acid and oleic acid.

  In the composition for external use of the present invention, the content of the higher fatty acid is not particularly limited, and for example, 0.001 to 0.1% by weight, preferably 0.005 to 0.1% by weight can be mentioned.

  In the composition for external use of the present invention, the ratio of ceramide to higher fatty acid is not particularly limited, but for example, 0.01 to 1000 parts by weight of higher fatty acid is preferable, preferably 1 part by weight of ceramides 1 to 3 in total. 0.1 to 500 parts by weight, more preferably 0.5 to 500 parts by weight can be mentioned.

(C) Nonionic Surfactant The composition for external use of the present invention contains a nonionic surfactant. In the composition for external use of the present invention, the non-ionic surfactant, together with the component (B) and the components (D) and (E) described later, contributes to the suppression of the formation of precipitates with time.

  The nonionic surfactant used in the present invention is not particularly limited as far as it is pharmaceutically or cosmetically acceptable, but preferably from the viewpoint of suppressing the formation of precipitates with time. An oxyethylene hydrogenated castor oil is mentioned.

  In polyoxyethylene hydrogenated castor oil, the addition mole number of ethylene oxide is not particularly limited, and in the composition for external use of the present invention, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 30, polyoxyethylene cured Castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 70, polyoxyethylene hydrogenated castor oil 80, polyoxyethylene hydrogenated castor oil 90, polyoxyethylene hydrogenated castor oil Any of 100 or the like may be used. Among these polyoxyethylene hydrogenated castor oils, polyoxyethylene hydrogenated castor oil 60 is preferably mentioned from the viewpoint of more effectively suppressing the formation of precipitates with time.

  In the composition for external use of the present invention, one type may be selected from nonionic surfactants and used alone, or two or more types may be used in combination.

  In the composition for external use of the present invention, the content of the nonionic surfactant is not particularly limited, and for example, 0.01 to 0.5% by weight, preferably 0.01 to 0.3% by weight can be mentioned. .

  In the composition for external use of the present invention, the ratio of ceramide to non-ionic surfactant is not particularly limited. There are 3000 parts by weight, preferably 1-2500 parts by weight.

(D) Polyhydric alcohol The composition for external use of the present invention contains a polyhydric alcohol. In the composition for external use of the present invention, the polyhydric alcohol, together with the components (B) and (C) and the component (E) described later, contributes to the suppression of the formation of precipitates with time.

  In the polyhydric alcohol used in the present invention, the valence of the hydroxyl group is not particularly limited, and examples thereof include 2 to 4 valences, preferably 2 to 3 valences.

  Specific examples of the polyhydric alcohol used in the present invention include dihydric alcohols such as ethylene glycol, propylene glycol, butylene glycol, pentanediol and dipropylene glycol; trihydric alcohols such as glycerin; and tetravalents such as diglycerin Alcohol and the like. Among these polyhydric alcohols, preferable are butylene glycol, propylene glycol, pentanediol, glycerin and dipropylene glycol.

  In the composition for external use of the present invention, one type may be selected from polyhydric alcohols and used alone, or two or more types may be used in combination.

  In the composition for external use of the present invention, the content of the polyhydric alcohol is not particularly limited, and examples thereof include 0.01 to 30% by weight, preferably 0.1 to 25% by weight.

  In the composition for external use of the present invention, the ratio of ceramide to polyhydric alcohol is not particularly limited, but, for example, 0.03 to 1500000 parts by weight of polyhydric alcohol per 1 part by weight of the total of ceramides 1 to 3 Preferably, 3.3 to 1250,000 parts by weight can be mentioned.

(E) Citric acid and / or its alkali metal salt The composition for external use of the present invention contains citric acid and / or its alkali metal salt. In the composition for external use of the present invention, citric acid and / or its alkali metal salt, together with the components (B) to (D), contributes to the suppression of the formation of precipitates with time.

  Specific examples of the alkali metal salt of citric acid used in the present invention include sodium salts of citric acid such as monosodium citrate, disodium citrate and trisodium citrate; monopotassium citrate, citric acid dibasic Examples thereof include potassium and potassium salts of citric acid such as tripotassium citrate.

  When citric acid is used, it is desirable to adjust the pH of the composition for external use of the present invention by adding an alkali containing an alkali metal such as sodium hydroxide or potassium hydroxide.

  In the composition for external use of the present invention, one kind of citric acid and alkali metals of citric acid may be selected and used alone, or two or more kinds may be used in combination. In particular, an alkali metal salt of citric acid, preferably a sodium salt of citric acid, more preferably trisodium citrate is preferably used from the viewpoint of more effectively suppressing the formation of precipitates with time.

  In the composition for external use according to the present invention, the content of citric acid and / or its alkali metal salt is not particularly limited, but for example, 0.001 to 1% by weight, preferably 0.01 to 0.6% by weight Be

(F) topical compositions of the water present invention contains water. In the composition for external use of the present invention, water serves as a substrate.

  In the composition for external use of the present invention, the content of water may be appropriately set according to the formulation form of the composition for external use, etc., but it is, for example, 50 to 99.9% by weight, preferably 60 to 95% by weight And more preferably 65 to 90% by weight.

Other Components In addition to the components (A) to (F), the composition for external use of the present invention may contain other pharmaceutically active ingredients as needed. Examples of such a medicinal component include antihistamines (diphenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics (procaine, tetracaine, bupipakine, mepipacain, mepipacain, chlorprocaine, proparacaine, meplarchain or their salts, orthokine, oxesazein, oxypoly entoxy). Deccan, roto extract, percamine pase, tesitdecitin etc., anti-inflammatory agents (indomethacin, felbinac, diclofenac sodium, loxoprofen sodium etc.), skin protective agents (collodione, castor oil etc.) , Capsaicin, red pepper extract, etc., refreshing agent (menthol, camphor, etc.), vitamins (vitamin A, etc.), mucopolysaccharides (chondroitte Sodium sulfate, glucosamine, etc.) and the like.

  In addition, the composition for external use may contain other base materials and additives as needed in order to obtain a desired formulation form. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable, but, for example, aqueous bases such as lower alcohols (ethanol, isopropanol etc.); oils (olive oil, safflower oil) , Soybean oil, camel oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil etc., mineral oil (liquid paraffin, paraffin, gelled hydrocarbon, vaseline etc), waxes and waxes (Beeswax, carnauba wax, candelilla wax, ceresin, rice wax, microcrystalline wax, etc.), ester oil (isopropyl myristate, isopropyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, ethyl oleate Etc), fatty acid Kyl ester, fatty acid ester (cetyl palmitate, isopropyl palmitate, ethyl linoleate, etc.), higher alcohol (stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol etc.), cholesterol, tri-2- Oil base such as glyceryl ethylhexanoate, cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone etc); zwitterionic surfactant, cationic surfactant, anionic surfactant etc Surfactants; refreshing agents (menthol, camphor, borneol, peppermint water, peppermint oil etc), preservatives (methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid etc), flavoring agents (sit , 1,8-cionere, citronellal, farnesol etc., coloring agents (tar pigment (brown 201, blue 201, yellow 4 etc. yellow), cocoa pigment, chlorophyll, aluminum oxide etc), sticky Consisting agents (carboxyvinyl polymer, hypromellose, polyvinylpyrrolidone, sodium alginate, ethylcellulose, carboxymethylcellulose sodium, xanthan gum, carrageenan etc.), pH adjusters (phosphoric acid, hydrochloric acid, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, trihydrate Ethanolamine, triisopropanolamine etc., wetting agent (sodium dl-pyrrolidone carboxylate solution, D-sorbitol solution, macrogol etc.), stabilizing agent (dibutylhydroxytoluene, butylhydroxyanisole, edetate nato) Sodium, sodium metaphosphate, L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc., antioxidants And additives such as UV absorbers, chelating agents, adhesives, buffers, solubilizers, solubilizers and preservatives.

Dosage form and use The dosage form of the composition for external use according to the present invention is not particularly limited as long as it can be applied transdermally, for example, lotion (skin water), hair lotion, milky lotion, body shampoo, hair shampoo, rinse Liquid preparations such as: semisolid preparations such as creams, gels, and ointments. Among these, preferably liquid preparations are mentioned. Among the liquid preparations, especially lotions and hair lotions, unlike emulsions and the like, it is difficult to mix sufficient amount of oil for facilitating dissolution of ceramide, and it is a preparation which is likely to cause precipitation over time. Regardless, it is a dosage form that requires high transparency. In the composition for external use of the present invention, even in the preparation form of lotion and hair lotion, the solubility of ceramide can be improved, precipitation formation with time can be effectively suppressed, and the preparation itself is translucent to transparent. It can also be done. In view of such effects of the present invention, lotions and hair lotions can be mentioned as suitable formulation forms of the composition for external use of the present invention.

  In addition, the composition for external use may be any formulation such as a cosmetic, a skin external preparation, a skin cleansing agent, etc. as long as it is applied to the skin (including the scalp), but preferably the cosmetic is It can be mentioned.

  The composition for external use according to the present invention can improve or properly maintain the barrier function and the moisturizing function of the stratum corneum based on the component (A), thereby improving moisturizing, roughening of the skin, elimination of sensitive skin, prevention of skin aging. Etc. can be used for skin care purposes.

Production method The production method of the composition for external use of the present invention is not particularly limited as long as it can be formulated in a state in which the component (A) is dissolved, but as a suitable example, through the following steps (1) to (3) The method of manufacturing is mentioned.
Step (1): The total amount of component (A), the total amount of component (B), the total amount of component (C), part of component (D), and lipophilicity among other components added as needed The mixture is heated and dissolved at about 90.degree. To 130.degree. C. to obtain a primary composition. In the step (1), the addition amount of the component (D) may be an amount corresponding to about 0.05 to 1% by weight, preferably about 0.1 to 1% by weight, in the final composition for external use .
Step (2): While heating the primary composition obtained in the above step (1) to about 90 to 130 ° C., gradually add a part of the component (F) heated to 90 ° C. or higher while stirring To obtain a secondary composition. In the step (2), the addition amount of the component (F) is 0.1 to 45% by weight, preferably 0.1 to 30% by weight, more preferably 0.1 to 10% by weight of the final composition for external use. It may be an amount corresponding to about% by weight, more preferably about 0.1 to 5% by weight.
Step (3): After the secondary composition obtained in the step (2) is cooled to about 40 ° C. or less, the remainder of the component (D), the total amount of the component (E), the remainder of the component (F), and The external use composition of the present invention is obtained by adding and mixing hydrophilic ones among other components added as needed. In the said process (3), cooling of a secondary composition may be performed by adding a part of (F) component of room temperature.

EXAMPLES The present invention will be more specifically described below by way of Examples, but the present invention is not limited thereto. In the following Examples and Comparative Examples, ceramide 1 is N- (27-stearoyloxyheptacosanoyl) phytosphingosine (trade name "CERAMIDEI
"Evonik Japan Co., Ltd.", Ceramide 2 uses stearoyl dihydrosphingosine (trade name "Ceramide TIC-001" Takasago Flavor Industrial Co., Ltd.), and Ceramide 3 uses stearoyl phytosphingosine (trade name "CERAMIDE III", Evonik Japan Co., Ltd.) did.

Examples 1 to 23
The external composition (lotion) of the composition shown to Tables 1-4 was manufactured. The specific manufacturing method is as follows.

First, the total amount of ceramide (ceramides 1 to 3), the total amount of isostearic acid or oleic acid, the predetermined amount of polyhydric alcohol shown below, and the total amount of polyoxyethylene hydrogenated castor oil 60 are mixed and heated to 120 ° C. Dissolve to obtain a primary composition.
(Type and amount of polyhydric alcohol added to primary composition)
Examples 1-19, 23, 26, 27 and 32: butylene glycol (the amount corresponding to 0.1% by weight in the final external composition),
Examples 21 and 24: Dipropylene glycol (amount corresponding to 0.1% by weight in the final external composition)
Examples 20, 25 and 29: Propylene glycol (the amount corresponding to 0.1% by weight in the final external composition)
Examples 22 and 28: Glycerin (amount corresponding to 0.1% by weight in the final composition for external use),
Example 30: butylene glycol (amount corresponding to 1% by weight in the final composition for external use)
Example 31: Glycerin (the amount corresponding to 1% by weight in the final composition for external use)

  Next, while heating the obtained primary composition to 120 ° C., gradually add a portion of purified water heated to 90 ° C. (an amount corresponding to about 0.35% by weight in the final composition for external use) The secondary composition was obtained. A portion of the purified water at room temperature (corresponding to about 0.5% by weight of the final external composition) is added to the obtained secondary composition at 100 ° C. or higher, and cooled to room temperature. The balance of polyhydric alcohol, the total amount of trisodium citrate (in the case of Examples 1 to 31), the total amount of citric acid and sodium hydroxide (in the case of Example 32), the total amount of phenoxyethanol (Examples 1 to 26, 31, And 32) and a mixture of the rest of purified water was added to produce a composition for external use (lotion).

After each obtained composition for external use was allowed to stand at room temperature for 5 days under light shielding conditions, the presence or absence of precipitation was visually confirmed, and the degree of precipitation after storage was evaluated according to the following judgment criteria.
<Criteria for determining the degree of formation of precipitates after storage>
◎: no formation of precipitates observed
○: The formation of a very small amount of precipitates is recognized, but this is not a problem in practical use.
Δ: The formation of precipitates is recognized to be a problem in practical use, but the amount of precipitates formed is not large.
X: The formation of many precipitates is recognized.
××: Remarkable formation of precipitates is observed.

  Tables 1 to 4 show the obtained results. From these results, in the externally applied composition containing two or more of ceramides 1 to 3 and water, higher fatty acid (isostearic acid or oleic acid), nonionic surfactant (polyoxyethylene hardened castor oil 60), Precipitation over time by incorporating polyhydric alcohol (butylene glycol, pentanediol, propylene glycol, dipropylene glycol, glycerin) and citric acid and / or alkali metal salt thereof (citric acid or trisodium citrate) It has been confirmed that it is possible to suppress the formation of and to provide excellent formulation stability. In particular, in the compositions for external use of Examples 16 to 32, even when three kinds of ceramides of ceramides 1 to 3 are combined, the formation of precipitates with time can be suppressed, and the preparation stability is remarkably improved. Was recognized. Moreover, all the compositions for external use of the Example were transparent, and were excellent in the external appearance.

Reference Examples 1 to 3 and Comparative Examples 1 to 16
The composition for external use (lotion) of the composition shown to Tables 5-7 was manufactured by the method similar to the said Example, and the grade of precipitation formation after storage was evaluated by the method similar to the said Example 1. FIG.

  The obtained results are shown in Tables 5-7. As apparent from Reference Examples 1 to 3, in the externally applied composition containing only one of ceramides 1 to 3, formation of precipitates with time was not observed even if trisodium citrate was not blended. That is, in the composition for external use containing ceramide, it was confirmed that the formation of precipitates with time is a unique problem when two or more of ceramides 1 to 3 are used in combination.

  Further, as apparent from Comparative Examples 1 to 10, in an external composition containing two or more of ceramides 1 to 3 and water, a higher fatty acid (isostearic acid), a nonionic surfactant (polyoxyethylene cured) Even if it contains castor oil 60) and polyhydric alcohols (butylene glycol, pentanediol, and glycerin), but does not contain citric acid and / or a salt thereof, formation of precipitates over time is observed. And could not provide sufficient formulation stability. Furthermore, even if salts of other organic acids (sodium tartrate, sodium gluconate, sodium lactate and sodium pyrrolidonecarboxylate) are used in place of citric acid and / or salts thereof from Comparative Examples 11 to 14 It was also confirmed that the formation of specific precipitates could not be suppressed.

  Furthermore, according to Comparative Examples 15 and 16, even when any one of higher fatty acid (isostearic acid) and nonionic surfactant (polyoxyethylene hydrogenated castor oil 60) is lacking, the formation of precipitates with time is suppressed. It was also confirmed that it could not be done.

  From the above results, the suppression of the formation of precipitates with time observed in Examples 1 to 32 is higher fatty acid and nonionic in the composition for external use containing two or more kinds of ceramides 1 to 3 and water. It has been confirmed that this is an effect obtained by integrally containing a surfactant, a polyhydric alcohol, and citric acid and / or an alkali metal salt thereof.

Formulation Examples 1 to 8: Lotion
An external composition (lotion) having a composition shown in Table 8 was produced according to the following method.

First, the total amount of ceramide (ceramides 1 to 3), the total amount of isostearic acid or oleic acid, the predetermined amount of polyhydric alcohol shown below, and the total amount of polyoxyethylene hydrogenated castor oil 60 are mixed and heated to 120 ° C. Dissolve to obtain a primary composition.
(Type and amount of polyhydric alcohol added to primary composition)
Formulation Examples 1 and 2: Glycerin (amount corresponding to 0.1% by weight in the final composition for external use)
Formulation Example 3: Glycerin (amount corresponding to 0.5% by weight in the final composition for external use)
Preparations 4 to 7: butylene glycol (equivalent to 0.1% by weight in the final composition for external use)
Formulation Example 8: butylene glycol (an amount corresponding to 1% by weight in the final external composition)

  Then, while heating the obtained primary composition to 120 ° C., gradually add a portion of purified water heated to 90 ° C. (the amount corresponding to 0.35% by weight in the final external composition) The secondary composition was obtained. A portion of purified water at room temperature (an amount corresponding to about 0.5% by weight of the final external composition) was added to the obtained secondary composition at 100 ° C. or higher, and cooled to room temperature. Thereafter, the composition for external use is added by adding a mixed solution in which the remaining portion of polyhydric alcohol, the total amount of trisodium citrate, the total amount of methylcelluloses -20, the total amount of sodium polyacrylate, the total amount of phenoxyethanol and the remaining portion of purified water Product (lotion) was manufactured.

  It was confirmed that all of the obtained compositions for external use can suppress the formation of precipitates with time as in the case of the above examples.

Formulation Example 9 Gel-like Lotion A composition for external use (gel-like lotion) having a composition shown in Table 9 was produced according to the following method.

  First, the total amount of ceramide (ceramides 1 to 3), the total amount of isostearic acid, a part of butylene glycol (an amount corresponding to 0.1% by weight in the final external composition), and the total amount of polyoxyethylene hydrogenated castor oil 60 The mixture was mixed and heated to 120.degree. C. to dissolve to obtain a primary composition.

  Then, while heating the obtained primary composition to 120 ° C., gradually add a portion of purified water heated to 90 ° C. (the amount corresponding to 0.35% by weight in the final external composition) The secondary composition was obtained. A portion of purified water at room temperature (an amount corresponding to about 0.5% by weight of the final external composition) was added to the obtained secondary composition at 100 ° C. or higher, and cooled to room temperature. Thereafter, the remaining portion of polyhydric alcohol, the total amount of trisodium citrate, the total amount of hydroxyethylcellulose, the total amount of carbomer, the total amount of sodium alginate, the total amount of methylparaben, the total amount of polyquaternium-51, the total amount of polyquaternium-61, the total amount of betaine, A solution obtained by mixing and dissolving the rest of the purified water was added at 40 ° C., mixed, and cooled to room temperature to produce an external composition (gel-like lotion).

  It was confirmed that the composition for external use obtained can suppress the formation of precipitates with time, as in the case of the above-mentioned examples.

Formulation Example 10 Hair Growth Lotion An external composition (hair growth lotion) having a composition shown in Table 10 was produced according to the following method.

  First, the total amount of ceramide (ceramides 1 to 3), the total amount of oleic acid, the total amount of propylene glycol, and the total amount of polyoxyethylene hydrogenated castor oil 60 are mixed, heated to 120 ° C. and dissolved to obtain a primary composition. The

  Then, while heating the obtained primary composition to 120 ° C., gradually add a portion of purified water heated to 90 ° C. (the amount corresponding to 0.15% by weight in the final external composition) The secondary composition was obtained. A portion of the purified water at room temperature (an amount corresponding to about 0.5% by volume of the final external composition) was added to the obtained secondary composition at 100 ° C. or higher, and cooled to room temperature. Thereafter, the total amount of trisodium citrate, the total amount of ethanol, the total amount of β-glycyrrhetinic acid, the total amount of hinokitiol, the total amount of DL-α-tocopherol acetate, the total amount of pyridoxine hydrochloride, the total amount of cerebrus extract, the total amount of aloe extract, The composition for external use (hair growth lotion) was manufactured by adding the liquid mixture which mixed the whole part of l-menthol and the remainder of purified water.

  It was confirmed that the composition for external use obtained can suppress the formation of precipitates with time, as in the case of the above-mentioned examples.

Claims (9)

(A) at least two ceramides selected from the group consisting of ceramide 1, ceramide 2 and ceramide 3, (B) higher fatty acid, (C) polyoxyethylene hydrogenated castor oil , (D) polyhydric alcohol, (E) An externally applied composition comprising citric acid and / or an alkali metal salt thereof, and (F) water.   The composition for external use according to claim 1, wherein the component (A) is a combination of ceramide 2 and ceramide 1 and / or ceramide 3. The composition for external use according to claim 1 or 2 , wherein the component (E) is a sodium salt of citric acid. The composition for external use according to any one of claims 1 to 3 , wherein the component (A) is contained in a total amount of 0.000001 to 0.05% by weight. The composition for external use according to any one of claims 1 to 4 , wherein the component (B) is contained in an amount of 0.001 to 0.1% by weight. The composition for external use according to any one of claims 1 to 5 , wherein the component (C) is contained in an amount of 0.01 to 0.5% by weight. The composition for external use according to any one of claims 2 to 6 , wherein 0.00001 to 10000 parts by weight of ceramide 1 and / or 0.00001 to 10000 parts by weight of ceramide 3 are contained per 1 part by weight of ceramide 2. The composition for external use according to any one of claims 1 to 7 , which is a cosmetic. The composition for external use according to any one of claims 1 to 8 , which is a lotion.