JP2002087926A - Permeation promoting skin care preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin permeation promoting agent having excellent skin permeation promoting effect and provide a skin care preparation having promoted skin permeability of active component. SOLUTION: A skin permeation promoting agent composed of 1,2-pentanediol is incorporated in a skin care preparation together with a physiologically active substance.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a skin penetration enhancer and an external preparation for skin containing the same.

[0002]

2. Description of the Related Art The skin is an organ that separates the human body from the external environment, and therefore has a function of preventing the invasion of substances from the outside. For this reason, if various inconveniences occur in the skin, for example, occurrence of inflammation, occurrence of pigment abnormality, occurrence of skin infection, occurrence of irregular stratum corneum, etc.
Preventing improvement or worsening involves great difficulties in terms of delivery of coping agents, in other words, impairment of transdermal absorption. Against this background, in the field of skin external preparations, especially in the field of cosmetics, researchers have focused on the development of technologies for promoting transdermal absorption and skin permeation enhancers (transdermal absorption enhancers). I was As a result, polyhydric alcohols such as 1,3-butanediol and propylene glycol, phospholipids such as phosphatidylcholine and phosphatidylglycerol, and heterocyclic compounds such as Aison have been found. However, the degree of its effect is unsatisfactory, and skin irritation is a problem with heterocyclic compounds, and further development has been desired.

[0003] On the other hand, 1,2-pentanediol is a component for a skin external preparation developed as a moisturizer having an antibacterial effect, and it promotes skin permeability of an active ingredient in the skin external preparation. No active ingredients such as 1,2-pentanediol and aromatic compounds, ascorbic acid and its derivatives, vitamin B group, triterpene-related substances or steroid skeletons, compounds having a flavone skeleton or an isoflavone skeleton have been known. Also, it was not known at all that it was contained in a skin external preparation.

[0004]

SUMMARY OF THE INVENTION The present invention has been made under such circumstances, and has an excellent skin permeation promoting effect.
An object of the present invention is to provide a skin permeation enhancer and an external preparation for skin in which the skin permeability of an active ingredient is promoted.

[0005]

In view of such circumstances, the present inventors have sought to provide a skin permeation enhancer having excellent skin permeation promoting effect and a skin external preparation having an enhanced skin permeability of an active ingredient. As a result of research efforts, 1,2-pentanediol was found to have an excellent skin permeation promoting effect of the active ingredient. As a result of further studies, it has been confirmed that a skin external preparation containing the same has excellent transdermal permeability of the active ingredient,
The invention has been completed. That is, the present invention relates to the following technology. (1) A skin permeation enhancer comprising 1,2-pentanediol. (2) An external preparation for skin, comprising the skin permeation enhancer according to (1) and a physiologically active substance. (3) The external preparation for skin according to (2), which is in the form of an emulsifier. (4) The external preparation for skin according to (2) or (3), which does not contain a nonionic surfactant having a polyoxyethylene group. (5) It is a cosmetic, (2) to (4)
The external preparation for skin according to any one of claims 1 to 7. (6) The external preparation for skin according to any one of (2) to (5), wherein the active ingredient has a cyclic structure. (7) The active ingredient is an aliphatic conjugated unsaturated compound, an aromatic compound, ascorbic acid and a derivative thereof, a vitamin B group,
(3) The external preparation for skin according to (6), which is at least one selected from triterpene-related substances and compounds having a steroid skeleton, a flavone skeleton or an isoflavone skeleton. (8) An external preparation for skin, comprising 1) 1,2-pentanediol and 2) a physiologically active substance. (9) The external preparation for skin according to (8), which is in an emulsified form. (10) (8) or (9), which does not contain a nonionic surfactant having a polyoxyethylene group.
2. The external preparation for skin according to item 1. (11) (8) to (1) being a cosmetic.
0) The external preparation for skin according to any one of the above. (12) The external preparation for skin according to any one of (8) to (11), wherein the active ingredient has a cyclic structure. (12) The active ingredient is an aliphatic conjugated unsaturated compound, an aromatic compound, ascorbic acid and its derivative, vitamin B
(1) one or more selected from a group, a triterpene-related substance and a compound having a steroid skeleton, a flavone skeleton or an isoflavone skeleton.
An external preparation for skin according to 1). Hereinafter, the present invention will be described in more detail focusing on embodiments.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION (1) Active ingredient which is an essential component of the skin permeation enhancer of the present invention and the external preparation for skin of the present invention The skin permeation enhancer of the present invention comprises 1,2-pentanediol. The skin permeation enhancer referred to in the present invention means a substance having a property that, when present together with the active ingredient, facilitates the penetration of the active ingredient through the skin and into the living body. 1,2-pentanediol, which is a skin permeation enhancer of the present invention, has already been used as a humectant having an antibacterial effect in the field of skin external preparations such as cosmetics, and its availability is commercially available. No obstacles. The skin permeability enhancer of the present invention remarkably promotes the permeability of the active ingredient, as shown in Examples described later. Such actions include aliphatic conjugated unsaturated compounds, triterpene rings, aromatic 6-membered rings,
Particularly, the skin permeability of a compound having a cyclic structure such as an aliphatic unsaturated heterocyclic 5- or 6-membered ring and a fused ring thereof is promoted. Preferred examples of the aliphatic conjugated unsaturated compound include vitamin A group compounds such as retinol, retinal, retinoic acid and / or salts thereof, dehydrocholesterol, vitamin D such as vitamin D3, and vitamin E such as tocopherol. Examples of compounds having a triterpene ring include glycyrrhizin, glycyrrhetinic acid and its esters, ursolic acid and its esters, and aromatic 6-membered ring compounds include kojic acid and its esters, ferulic acid and its esters Examples of the hydroquinone and its glycosides, alkyl polyphenols, and aliphatic unsaturated 5- or 6-membered rings include ascorbic acid, ascorbic acid glycosides, esters and / or salts thereof, and the like. Examples of these condensed rings include flavones, Rabon acids, such flavans can be exemplified. Of these, particularly preferred is 2′-
Hydroxy-2,4,4,7,4'-pentamethylflavan (hereinafter referred to as compound 1) and / or a salt thereof. This is a known substance having the chemical structure shown in Chemical formula 1 and having a known melanin production inhibitory action. The method for producing this is already known, and can be obtained, for example, by condensing m-cresol in anhydrous acetone-based hydrogen chloride and neutralizing with a strong alkali. Salts thereof include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, ammonium salts, organic amine salts such as triethanolamine salts and triethylamine salts, and bases such as lysine salts and arginine salts. A preferred example is a sex amino acid salt. The preferred content of the active ingredient, which is an essential component of the external preparation for skin of the present invention, in the external preparation for skin of the present invention is 0.001 to 10% by weight, although it differs depending on each medicinal effect.
More preferably, it is 0.01 to 3% by weight. In the skin external preparation of the present invention, since the skin permeability is enhanced, the content may be lower than that of a normal skin external preparation.

[0007]

Embedded image 2'-hydroxy-2,4,4,7,4'-pentamethylflavan (compound 1)

[0008] In order to exhibit the skin permeability promoting action of the active ingredient, 1,2-pentanediol is used in an amount of 1 to 20% by weight, more preferably 3 to 20% by weight, based on the total amount of the external preparation for skin.
Preferably, it is contained in an amount of about 15% by weight. Since 1,2-pentanediol exerts a moisturizing action or an antibacterial action in an external preparation for skin, even if it is an external preparation containing 1,2-pentanediol for such a purpose, it coexists with an active ingredient. In such a case, since the effects of the present invention are exhibited, such external preparations for skin can be said to belong to the technical scope of the present invention.

(2) External preparation for skin of the present invention The external preparation for skin of the present invention is an essential component as described above.
It is characterized by containing 1,2-pentanediol and an active ingredient. In the external preparation for skin of the present invention, the use thereof can be applied without any particular limitation such as a medicine for external use on the skin, a disinfectant for external use of the skin, and cosmetics. The effect is particularly remarkable when applied to a cosmetic having a low active ingredient concentration, which is preferable. The external preparation for skin of the present invention can be applied without particular limitation as long as it is a dosage form generally known as an external preparation for skin, for example, a solubilizing system such as a lotion or a microemulsion system, an emulsion or a cream. Examples thereof include an emulsification system including a multiphase emulsification system, an oil gel dispersion system, and a gel agent system. Of these, particularly preferred are emulsified systems,
Among them, it is an emulsification system which does not contain a nonionic surfactant having a polyoxyethylene group. Particularly preferred examples of such a system include acrylic acid and acrylic acid (C10-3
0) A system in which an alkyl copolymer ("Pemulene") and / or a salt thereof is emulsified using 0.1 to 2% by weight. This is because the influence of the nonionic surfactant having a polyoxyethylene group, which is a factor that causes a change in skin permeability of the active ingredient, can be removed, and a stable skin permeation amount can be secured.

The external preparation for skin of the present invention may contain, in addition to the above-mentioned components, any components usually used in external preparations for skin. Such optional components include, for example, hydrocarbons such as squalane, petrolatum, microcrystalline wax, silicones such as dimethicone and femethicone, jojoba oil, carnauba wax, esters such as octyldodecyl oleate, olive oil, Triglycerides such as beef tallow and coconut oil, fatty acids such as stearic acid, oleic acid and ritinoleic acid, higher alcohols such as oleyl alcohol, stearyl alcohol and octyldodecanol, and polyvalents such as polyethylene glycol, glycerin and 1,3-butanediol Examples thereof include alcohols, thickening / gelling agents, antioxidants, ultraviolet absorbers, coloring agents, preservatives, and powders. Of course, it is needless to say that an external medicine for skin can contain an active ingredient such as an antifungal agent, an anti-inflammatory agent or a steroid. Among these components, particularly preferred are silicones such as dimethicone, which have the effect of further enhancing the effect of promoting the permeability of the active ingredient, and can exhibit such effects efficiently. The content is preferably 1 to 10% by weight. It is also advantageous to include serakyl alcohol in order to stabilize the system and enhance the skin knitting adhesion of the composition. The addition of this can stabilize the emulsified system. Further, as a secondary effect, it exerts the effect of improving the adhesion between the external preparation for skin and the skin and further improving the skin permeability of the active ingredient physically. The preferred content of seraalkyl alcohol in the skin external preparation of the present invention is 0.05 to 10% by weight, more preferably 0.1 to 10% by weight.
1 to 5% by weight. The external preparation for skin of the present invention can be produced by treating the above essential components with optional components or preferable components according to a conventional method.

[0011]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but it goes without saying that the present invention is not limited to only these Examples.

<Examples 1 and 2> An emulsion (cosmetic), which is an external preparation for skin of the present invention, was prepared according to the following formulation. That is, (a), (b) and (c) were heated to 70 ° C., (b) was neutralized by adding (b), emulsified by gradually adding (c) while stirring, the particles were adjusted with a homogenizer, and the mixture was stirred and cooled to obtain an emulsion.
For these emulsions, Comparative Example 1, in which 1,2-pentanediol of Example 1 was replaced with propylene glycol,
Comparative Example 2 in which 1,3-butanediol was substituted and Control Example 1 in which water was substituted were prepared, and a shaving skin on the back of a guinea pig was attached to a Franz type permeation cell, and 0.2 ml of an emulsion was applied to a donor site. Then, the amount of Compound 1 permeated through the skin when the receiver site was filled with physiological saline and allowed to stand at 37 ° C. for 40 hours was measured by high performance liquid chromatography according to the absolute calibration curve method. (ODS column, 30% acetonitrile aqueous solution, 240 nm) Transfer amount (μg / cm 2) is shown in Table 1. This shows that the external preparation for skin of the present invention is excellent in promoting skin permeability. This is apparently due to the effect of the skin permeation enhancer of the present invention. I pemulene 0.3 parts by weight (acrylic acid / alkyl (C10-30) acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol * water * b water 20 parts by weight 10% by weight potassium hydroxide aqueous solution 1.3 Parts by weight C Compound 1 1.5 parts by weight Seraquil alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight 0.1 parts by weight butyl paraben * Details are shown in Table 1.

[0013]

[Table 1]

<Example 3> In the same manner as in Examples 1 and 2, an emulsion for external use on the skin of the present invention was prepared. This one, two
Comparative Example 3 in which pentanediol was replaced by propylene glycol and Control Example 2 in which water was replaced by propylene glycol were also prepared. Regarding these, the inner side of the upper arm was irradiated with ultraviolet rays A of 0.9 MED five times continuously, and the examination was performed using the degree of improvement of the sun turn as an index. That is, the sun turn part (2cm x 2cm)
Was administered once a day for 5 consecutive days, and 72 hours after the last administration, the difference from the untreated site was determined using a colorimeter.
Table 2 shows the results of measuring the L value. This indicates that the external preparation for skin of the present invention has excellent skin permeability. I pemulene 0.3 parts by weight (acrylic acid / (C10-30) alkyl acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol 8 parts by weight arbutin 3 parts by weight water 58.8 parts by weight b water 20 parts by weight 10% by weight aqueous solution of potassium hydroxide 1.3 parts by weight C Serakil alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight 0.1 parts by weight butyl paraben

[0015]

[Table 2]

Example 4 In the same manner as in Examples 1 and 2, an emulsion (cosmetic) as an external preparation for skin of the present invention was prepared. It was excellent in anti-inflammatory action. I Pemulen 0.3 parts by weight (acrylic acid / alkyl (C10-30) acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol 8 parts by weight Sodium glycyrrhetinate 0.1 part by weight Water 61.7 parts by weight b Water 20 parts by weight 10% by weight aqueous solution of potassium hydroxide 1.3 parts by weight C Serakyl alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight 0.1 parts by weight butyl paraben

Example 4 In the same manner as in Examples 1 and 2, an emulsion (cosmetic) as an external preparation for skin of the present invention was prepared. This was excellent in whitening effect. I pemulene 0.3 parts by weight (acrylic acid / alkyl (C10-30) acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol 8 parts by weight 2 magnesium magnesium ascorbate 0.5 parts by weight Water 61.3 parts by weight Part b Water 20 parts by weight 10% by weight aqueous solution of potassium hydroxide 1.3 parts by weight C Serakyl alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight 0.1 parts by weight butyl paraben

Example 5 In the same manner as in Examples 1 and 2, an emulsion (cosmetic) as an external preparation for skin of the present invention was prepared. This was excellent in anti-skin roughening action. I pemulene 0.3 parts by weight (acrylic acid / alkyl (C10-30) acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol 8 parts by weight water 61.7 parts by weight b water 20 parts by weight 10% by weight water Aqueous potassium oxide solution 1.3 parts by weight C vitamin E nicotinate 0.1 parts by weight Seraky alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight butyl paraben 0.1 parts by weight

<Example 6> In the same manner as in Examples 1 and 2, an emulsion (cosmetic) as a skin external preparation of the present invention was prepared. This was excellent in anti-skin roughening action. I pemulene 0.3 parts by weight (acrylic acid / alkyl (C10-30) acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol 8 parts by weight water 61.7 parts by weight b water 20 parts by weight 10% by weight water Aqueous potassium oxide solution 1.3 parts by weight Habenzyl ureate 0.1 parts by weight Seraky alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight butyl paraben 0.1 parts by weight

<Example 7> In the same manner as in Examples 1 and 2, an emulsion (external medicine for skin) as an external preparation for skin of the present invention was prepared.
It was excellent in anti-inflammatory action. I pemulene 0.3 parts by weight (acrylic acid / alkyl (C10-30) acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol 8 parts by weight water 60.8 parts by weight b water 20 parts by weight 10% by weight water Potassium oxide aqueous solution 1.3 parts by weight Hindomethacin 1 part by weight Serakyl alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight 0.1 parts by weight butyl paraben

<Example 5> In the same manner as in Examples 1 and 2, an emulsion (external medicine for skin) as an external preparation for skin of the present invention was prepared.
This was excellent in antifungal action. I pemulene 0.3 parts by weight (acrylic acid / alkyl (C10-30) acrylate) methyl paraben 0.2 parts by weight 1,2-pentanediol 8 parts by weight water 59.8 parts by weight b water 20 parts by weight 10% by weight water Potassium oxide aqueous solution 1.3 parts by weight Honey terbinafine 2 parts by weight Serakyl alcohol 0.3 parts by weight Isopropyl myristate 2.4 parts by weight Dimethicone 5.6 parts by weight 0.1 parts by weight butyl paraben

[0022]

According to the present invention, it is possible to provide a skin permeation enhancer which is excellent in skin permeation promoting effect and a skin external preparation in which the skin permeability of an active ingredient is promoted.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/19 A61K 31/19 31/355 31/355 31/375 31/375 31/405 31/405 47 / 10 47/10 A61P 17/00 A61P 17/00 17/16 17/16 29/00 29/00 31/10 31/10 F term (reference) 4C076 AA12 AA16 BB31 CC05 CC18 DD30 DD37 DD38N DD41 DD45 EE09 EE10 EE27 FF34 4C083 AB032 AC072 AC111 AC112 AC352 AC482 AC532 AC841 AC852 AD092 AD152 AD412 AD491 AD531 AD532 AD631 AD641 AD642 AD661 AD662 CC05 DD31 EE03 EE13 EE16 4C086 AA02 BA09 BA18 BC15 MA02 MA05 NA11 ZA89 ZB11 ZC12 MA9 ZC24 ZC28 ZC29

Claims (13)

[Claims] 1. A skin permeation enhancer comprising 1,2-pentanediol. 2. An external preparation for skin comprising the skin permeation enhancer according to claim 1 and a physiologically active substance. 3. The external preparation for skin according to claim 2, which is in an emulsified form. 4. The external preparation for skin according to claim 2, which does not contain a nonionic surfactant having a polyoxyethylene group. 5. The external preparation for skin according to claim 2, wherein the external preparation is a cosmetic. 6. The external preparation for skin according to any one of claims 2 to 5, wherein the active ingredient has a cyclic structure. 7. The active ingredient is an aliphatic conjugated unsaturated compound,
Aromatic compounds, ascorbic acid and its derivatives, vitamin B group, triterpene-related substances and steroid skeleton,
One or more compounds selected from compounds having a flavone skeleton or isoflavone skeleton,
The skin external preparation according to claim 6. 8. An external preparation for skin, comprising 1) 1,2-pentanediol and 2) a physiologically active substance. 9. The external preparation for skin according to claim 8, which is in an emulsified dosage form. 10. The method according to claim 8, wherein the composition does not contain a nonionic surfactant having a polyoxyethylene group.
Or the external preparation for skin according to 9. 11. The external preparation for skin according to any one of claims 8 to 10, which is a cosmetic. 12. The external preparation for skin according to any one of claims 8 to 11, wherein the active ingredient has a cyclic structure. 13. The active ingredient is one selected from aliphatic conjugated unsaturated compounds, aromatic compounds, ascorbic acid and its derivatives, vitamin B group, triterpene-related substances, and compounds having a steroid skeleton, flavone skeleton or isoflavone skeleton. The skin external preparation according to claim 11, wherein the external preparation is at least two kinds.