JP2704759B2 - Glyceryl ether derivative and external preparation for skin containing the same - Google Patents

Description

The present invention relates to a glyceryl ether derivative and an external preparation for skin containing the same, more specifically, a glyceryl ether derivative of cholesterol or cholestanol and a water content of the stratum corneum containing the same. The present invention relates to an external preparation for skin that can increase the holding power, increase the flexibility and elasticity of the skin, and improve the rough skin.

[Conventional technology]

It is known that cholesterol exists widely in nature and is distributed in almost all tissues, particularly brain cranial tissues of animals, and plays an extremely physiologically important role. For example, in biological membranes, cholesterol is thought to be an important component in strengthening the membrane structure.In skin, cholesterol is contained in skin secretions and is important for maintaining skin emolliency. Playing a role. Therefore, cholesterol is regarded as an important raw material for pharmaceutical synthesis.

In addition, cholesterol has W / O-like emulsifying ability, which enhances the emulsification stability of creams and emulsions and improves the emollient on the skin to increase flexibility and elasticity to the skin It has been known for a long time that it has been used as a base for cosmetics.

[Problems to be solved by the invention]

However, since cholesterol is an oil-soluble and high-melting solid, special measures must be taken for its use, and there is a drawback that its use in lotions and emulsification systems with a high water content is limited. In addition, since the emollient property cannot fundamentally improve the water retention ability of the stratum corneum, it has a problem that it does not essentially prevent or cure skin roughness.

[Means for solving the problem]

Under such circumstances, the present inventors have conducted intensive studies to solve the above problems, and as a result, newly synthesized glyceryl ether derivatives of cholesterol or cholestanol have recently been used to improve the emulsion stability of skin external preparations such as lotion. The present invention has been found to have an effect of improving the water retention ability of the skin keratin in addition to improving the skin moisture, and completed the present invention.

That is, the present invention provides the following general formula (I) (In the formula, R ₁ is a saturated or unsaturated linear or branched hydrocarbon group or acyl group having 1 to 22 carbon atoms, or 2,3
-Represents a dihydroxypropyl group, R ₂ is a hydrogen atom or 2,
A glyceryl ether derivative of cholesterol or cholestanol represented by the formula: and an external preparation for skin containing the same.

In the general formula (I), examples of the saturated or unsaturated linear or branched hydrocarbon group having 1 to 22 carbon atoms represented by R ₁ include methyl, ethyl, n-propyl, n-pentyl, and n-pentyl. Hexyl, n-heptyl, n-octyl, n-
Nonyl, n-decyl, n-undecyl, n-dodecyl,
linear primary alkyl groups such as n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl, n-eicosyl, n-heneicosyl, n-docosyl;
-Ethylhexyl, 2-butyldecyl, 2-ethyldodecyl, 2-butyldodecyl, 2-ethyltetradecyl,
2-hexyldecyl, 2-butyltetradecyl, 2-ethylhexadecyl, 2-hexyldecyl, 2-butylhexadecyl, 2-ethyloctadecyl, 2-hexyltetradecyl, 2-octyldodecyl, 2-butyloctadecyl, Ethyleicosyl, 2-hexylhexadecyl, 2-octyltetradecyl, 2-heptylundecyl, 2- (1,3,3-trimethylbutyl) octyl,
5,7,7-trimethyl-2- (1,3,3-trimethylbutyl)
Octyl and the following formula [Wherein, m represents an integer of 4 to 10, n represents an integer of 5 to 11, m + n represents 11 to 17, and m = 7, and n has a distribution having n = 8 as a vertex.] Branched-chain primary saturated alkyl group such as methyl-branched isostearyl group; 2-propyl, sec
-Butyl, sec-pentyl, sec-hexyl, sec-heptyl, sec-octyl, sec-nonyl, sec-decyl, sec
Secondary unsaturated alkyl groups such as -undecyl and sec-dodecyl groups; vinyl, allyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl And alkenyl groups such as eicosenyl, heneicosenyl and docosenyl groups. Examples of the acyl group include an alkanoyl group and an alkenoyl group corresponding to the alkyl group or the alkenyl group.

The glyceryl ether derivative of cholesterol or cholestanol represented by the general formula (I) in the present invention is disclosed in West German Patent No. 2,535,778, JP-B-63-24496,
It can be produced, for example, by any of the following methods (1) to (4) by utilizing the methods described in JP-B-64-9304 and JP-A-58-134049.

(1) A glyceryl ether derivative (III) in which R ₁ is a linear or branched alkyl group, alkenyl group or acyl group having 1 to 22 carbon atoms and R ₂ is a hydrogen atom can be prepared, for example, according to the reaction formula shown below. Manufactured.

[Wherein, R ₁ ′ represents a linear or branched alkyl group, alkenyl group or acyl group having 1 to 22 carbon atoms] That is, epichlorohydrin is first added to cholesterol or cholestanol in the presence of an aqueous alkali solution, and a phase transfer catalyst is used. And glycidyl ether derivative (II) is obtained.

Sodium hydroxide aqueous solution as the alkaline aqueous solution,
Examples of the phase transfer catalyst include tetrabutylammonium hydrogensulfate and tetrabutylammonium bromide.
Quaternary ammonium salts, but are not necessarily limited thereto. The amount of the aqueous alkali solution used is preferably 2 to 10 equivalents, more preferably 3 to 6 equivalents to cholesterol or cholestanol, and the amount of the phase transfer catalyst is 0.01 to 0.2 equivalents, particularly to cholesterol or cholestanol.
0.03-0.1 equivalents are preferred. The amount of epichlorohydrin used is preferably 1 to 5 equivalents, particularly preferably 1.5 to 3 equivalents, based on cholesterol or cholestanol. As the solvent, a hydrocarbon solvent such as n-hexane and toluene is usually used. The reaction temperature is preferably from 40 to 100 ° C, particularly preferably from 50 to 60 ° C.

Further, when the glycidyl ether derivative (II) is reacted with an excess amount of alcohols or fatty acids (R ′ ₁ OH) in the presence of a catalyst, the glyceryl ether derivative (III) is obtained.

Examples of the catalyst used herein include alkali metal catalysts such as sodium metal and sodium methylate; tertiary amine catalysts such as triethylamine and N, N, N ', N'-tetramethylhexamethylenediamine; SnCl ₂ , BF ₃ .OBt _And a Lewis acid catalyst such as ₂ . The amount of the catalyst used is preferably 0.01 to 0.2 equivalent relative to the glycidyl ether derivative (II), and the reaction temperature is preferably room temperature to 150 ° C.

(2) The glyceryl ether derivative (V) in which R ₁ is a 2,3-dihydroxypropyl group and R ₂ is a hydrogen atom is 2,2-dimethyl-1,3-dioxolan-4- as an alcohol.
The glyceryl ether derivative (IV) produced in the same manner as described above except that methanol is used is hydrolyzed in the presence of an acid catalyst according to the following reaction formula.

Examples of the acid catalyst include those used in ordinary hydrolysis reactions such as hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, and acetic acid, and are used in an amount of 0.01 to glyceryl ether derivative (IV).
~ 0.2 equivalents are used. The reaction is preferably carried out in a mixed solvent system of lower alcohols such as methanol, ethanol and isopropanol and water, and the reaction temperature is 50
-100 ° C, especially 70-90 ° C, is preferred.

(3) The glyceryl ether derivative (VIII) in which R ₁ is a linear or branched alkyl or alkenyl group having 1 to 22 carbon atoms and R ₂ is a 2,3-dihydroxypropyl group is the glyceryl ether prepared above. It can be produced from the derivative (III) according to the reaction formula shown below.

Wherein R ₁ 'has the same meaning as described above. To produce the glycidyl ether derivative (VI) from the glyceryl ether derivative (III), the glycidyl ether derivative (II) must be obtained from cholesterol or cholestanol. The same reaction operation as described above may be performed.
However, the solvent need not always be used depending on the type of the glyceryl ether derivative (III) as a raw material. In addition, the reactivity of the glyceryl ether derivative (III) is low depending on the type of the glyceryl ether derivative (III).
In some cases, conversion to I) is not sufficient. In that case, however, the conversion to glycidyl ether derivative (VI) can be increased by removing only the organic layer from the reaction mixture and repeating the reaction again under the same conditions.

Next, the diacetate derivative (VII) can be produced by reacting the glycidyl ether derivative (VI) with an excess amount of acetic anhydride in the presence of a tertiary amine catalyst such as triethylamine.

Here, the use amount of the tertiary amine catalyst is preferably 0.05 to 0.2 equivalent to glycidyl ether derivative (VI), and acetic anhydride is at least twice equivalent to glycidyl ether derivative (VI), particularly 6 to 12 equivalents. It is preferably a double equivalent. The reaction temperature is preferably from 80 to 120 ° C.

The obtained diacetate derivative (VII) can be easily converted to a glyceryl ether derivative (VIII) by hydrolysis using a usual alkali catalyst.

Examples of the alkali catalyst include sodium hydroxide, potassium hydroxide, potassium carbonate and the like. If the reaction is carried out in an aqueous alcohol solution such as ethanol, methanol, or isopropanol at 60 to 80 ° C., the reaction proceeds easily, and the desired glyceryl ether derivative (VIII) can be obtained.

(4) The glyceryl ether derivative of cholestanol is
It can also be produced by catalytic reduction of a glyceryl ether derivative of cholesterol in the presence of a suitable metal catalyst.

Examples of the metal catalyst used here include metals such as platinum, palladium, rhodium and nickel, and metal oxides thereof. As the solvent, for example, water, alcohols, ethyl acetate, dioxane, tetrahydrofuran and the like are used, and an acid such as acetic acid, hydrochloric acid, sulfuric acid and perchloric acid may be added to these solvents. Hydrogen can be easily converted to a cholestanol derivative by acting at normal pressure or preferably under slightly elevated pressure and heating at room temperature or preferably at 50 to 80 ° C.

The amount of the glyceryl ether derivative of cholesterol or cholestanol (I) to be added to the external preparation for skin of the present invention is not particularly limited. %), Especially
0.1-20% is preferable, and in the case of oily skin external preparations based on liquid hydrocarbons such as squalene, 1-50%,
Particularly, 5 to 25% is preferable.

In addition, it is preferable that the skin external preparation of the present invention contains a surfactant as an emulsifier. As these surfactants, any of a nonionic surfactant, an anionic surfactant and an amphoteric surfactant is used. Although possible, non-ionic surfactants are particularly preferred.

Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene fatty acid ester,
Examples include sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, fatty acid monoglycerides, glyceryl ethers, and the like. Among them, the following general formula (IX) [Wherein R represents an alkyl group having 8 to 24 carbon atoms] glyceryl ether represented by the following formula: [Wherein, p represents an integer of 4 to 10, and q represents an integer of 5 to 11,
p + q = 11 to 17 and a distribution having apexes of p = 7 and q = 8] is particularly preferable.

The amount of the surfactant is 0.01 to 20% of the total composition, particularly 0.1%.
It is preferably 1 to 5%.

The skin external preparation of the present invention is roughly classified into a medicated skin external preparation and a cosmetic in its use form.

Examples of the medicated skin external preparation include various ointments containing a pharmaceutically active ingredient. The ointment may be any of those based on an oily base and those based on an oil / water or water / oil type emulsified base. The oil base is not particularly limited and includes, for example, vegetable oil, animal oil, synthetic oil, fatty acid, and natural or synthetic glyceride. The medicinal component is not particularly limited, and for example, an analgesic / anti-inflammatory agent, an antipruritic agent, a germicidal disinfectant, an astringent, an emollient, a hormonal agent, and the like can be used as needed.

In addition, when used as a cosmetic, in addition to the essential ingredients, oils, humectants, which are generally used as cosmetic ingredients,
UV absorbers, alcohols, chelating agents, pH adjusters,
Preservatives, thickeners, pigments, fragrances and the like can be combined in any combination.

Examples of cosmetics include various forms such as water / oil, oil / water emulsified cosmetics, creams, emulsions, lotions, oily cosmetics, lipsticks, foundations, skin cleansers, hair tonics, hair styling agents, hair tonics, It can be used as a skin cosmetic such as a hair restorer.

[Action]

The details of the action mechanism of the glyceryl ether derivative of cholesterol or cholestanol represented by the formula (I) in the external preparation for skin of the present invention have not been completely elucidated, but by adding this, the lipid membrane between the keratinocytes is regenerated. It is thought to help with construction and exert the water retention function of the stratum corneum.

〔The invention's effect〕

Since the skin external preparation of the present invention contains a glyceryl ether derivative of cholesterol or cholestanol having such an action, it can exhibit excellent improvement and prevention effects on rough skin.

〔Example〕

 Next, the present invention will be described with reference to examples.

Example 1 1-0-cholesteryl-3-0-methylglycerin (I
a): (i) Cholesterol 15 was added to a flask equipped with a reflux condenser, a thermometer, a dropping funnel, a N ₂ gas inlet tube and a stirrer.
4.6 g (0.4 mol), toluene 309.2 g, epichlorohydrin
111.0 g (1.2 mol) and 6.8 g (0.02 mol) of tetrabutylammonium hydrogen sulfate were charged and heated to 50 ° C. while stirring under N ₂ gas introduction. Sodium hydroxide 80g (2.0
mol) was added dropwise over 30 minutes with vigorous stirring, and stirring was continued at 50 to 60 ° C for 6 hours. The reaction mixture was washed with water in order to remove the salt thus formed, and 37.2 g (0.4 mol) of epichlorohydrin and 3.4 g (0.01 mol) of tetrabutylammonium hydrogen sulfate were added. ) Was added dropwise at 40 ° C over 30 minutes. 6 more at 45-50 ° C
After stirring vigorously for an hour, the reaction mixture was washed with water, and unreacted cholesterol and the like were removed by column chromatography purification using 500 g of silica gel to obtain 154.4 g (0.349 mol) of cholesteryl glycidyl ether. Yield 87.2%.

Melting point 70-73 ° C ¹ H-NMR δ ppm (CDCl ₃ , TMS standard) 0.6-2.4 (m, 43H) 2.58-2.64 (m, 1H) 2.76-2.82 (m, 1H) 3.06-3.24 (m, 2H) 3.42 −3.80 (m, 2H) 5.34 (d, 1H, J = 5.0 Hz) IR (ν: cm ⁻¹ ) 2940, 1470, 1382, 1110, 843 (ii) Reflux cooler, dropping funnel, thermometer and stirrer 256 g (8.0 mol) of methanol and MeO in a 500 ml flask equipped with
Add 7.6 g (0.04 mol) of Na (28% methanol solution) and add 55 to 6
The mixture was heated and stirred at 5 ° C. 94.5 g (0.213 mol) of cholesteryl glycidyl ether obtained in Example 1 (i) was added dropwise thereto over 2 hours while stirring.
Stirring was continued for hours. After completion of the reaction, the mixture was neutralized with 6N-HCl, and methanol was distilled off under reduced pressure. After dissolving the residue in n-hexane, the desired 1-0 was purified by flash chromatography using 1.0 kg of silica gel (Merck Art 9385) (n-hexane / ethyl acetate = 2/1 as a solvent).
92.0 g of cholesteryl-3-0-methylglycerin (0.2
0 mol) was obtained as a colorless solid. 93.9% yield.

84-87 ° C ¹ H NMR δ ppm (CDCl ₃ , TMS standard) 0.7-2.4 (m, 43H) 2.64 (br, 1H) 3.10-3.26 (m, 1H) 3.39 (s, 3H) 3.42-3.60 (m, 4H 3.88−3.96 (m, 1H) 5.34 (d, 1H, J = 5.1 Hz) IR (ν: cm ⁻¹ ) 3454, 2938, 1470, 1383, 1107 Example 2 1-0-Cholesteryl-3-0- Methyl-branched isostearyl glycerin (Ib): Methyl-branched isostearyl alcohol (a methyl-branched isostearine commercially available from Emery, USA) is placed in a 300 ml flask equipped with a reflux condenser, a dropping funnel, a thermometer, an N ₂ gas inlet tube and a stirrer. 135.3g adjusted from acid)
(0.5 mol), and under the introduction of N ₂ gas, 0.1% of metallic sodium was added.
69 g (0.03 mol) was added and stirred at 60 ° C. until completely dissolved. Next, 47.3 g (0.107 mol) of cholesteryl glycidyl ether obtained in Example 1 (i) was stirred at 60 ° C.
And drop it over 1 hour.
Stirred for 24 hours. After completion of the reaction, excess alcohol was distilled off under reduced pressure, extracted with dichloromethane, and washed with water. Then, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the objective 1-0-cholesteryl-3-0-methyl-branched isostearylglycerin.
61.9 g (0.0868 mol) were obtained. Yield 81.1%. ¹ H-NMR δ ppm (CDCl ₃ , TMS standard) 0.7-2.4 (m, 78H) 2.58 (br, 1H) 3.10-3.26 (m, 1H) 3.40-3.60 (m, 6H) 3.88-3.98 (m, 1H) 5.34 (d, 1H, J = 5.0 Hz) IR (ν: cm ⁻¹ ) 3452, 2944, 1470, 1383, 1110 Example 3 1-0-Cholesteryl-3-0- (2,3-dihydroxypropyl)- Glycerin (Ic): (i) In Example 2, instead of methyl branched isostearyl alcohol, 2,2-dimethyl-1,3-dioxolane-
2,2-Dimethyl-4- (2′-) was prepared in the same manner as in Example 2 except that 260.4 g (2.0 mol) of 4-methanol was used.
47.7 g (0.083 mol) of hydroxy-3'-cholesteryloxy) propoxymethyl-1,3-dioxolane were obtained. yield
77.7%.

Melting point 78-80 ° C ¹ H-NMR δ ppm (CDCl ₃ , TMS standard) 0.7-2.4 (m, 1H) 2.87 (m, 1H) 3.09-3.23 (m, 1H) 3.42-3.67 (m, 6H) 3.68-3.78 (M, 1H) 3.93 (m, 1H) 4.05 (m, 1H) 4.28 (m, 1H) 5.34 (d, 1H, J = 4.8 Hz) IR (ν: cm ^-1 ) 3454, 2944, 1470, 1383, 1086 (ii) The 2,2-dimethyl-4- (2′-hydroxy-3 ′) obtained in Example 3 (i) was placed in a 500 ml flask equipped with a reflux condenser, a thermometer, a N ₂ gas inlet tube and a stirrer. -Cholesteryloxy) propoxymethyl-1,3-dioxolane 44.2 g (0.
0769mol), methanol 220g, concentrated sulfuric acid 1.43g (0.0145mo
l) and water (13.2 ml) are added, and N ₂ gas is introduced for 2 hours at 64 to 65 ° C.
And heated to reflux. After completion of the reaction, the mixture was neutralized with an aqueous sodium hydroxide solution and extracted with a mixed solvent of ether and toluene.
After the organic layer was washed with water, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 35.2 g (0.0658 g of the objective 1-0-cholesteryl-3-0- (2,3-dihydroxypropyl) glycerin. mol).
85.6% yield.

Melting point 198-201 ° C ¹ H-NMR δppm (CDCl ₃ , TMS standard) 0.7-2.4 (m, 43H) 3.10-3.25 (m, 1H) 3.47-4.03 (m, 13H) 5.34 (d, 1H, J = 4.1) Hz) IR (ν: cm ⁻¹ ) 3406, 2944, 1470, 1383, 1110 Example 4 1-0-Cholesteryl-3-0-methyl-2-0-
2 ', 3'-dihydroxypropylglycerin (Id): (i) 1-0-cholesteryl-3-0 obtained in Example 1 (ii) instead of cholesterol in Example 1 (i).
1-0-cholesteryl-3-0-methyl-2-0-2 ', 3'-epoxy was prepared in substantially the same manner as in Example 1 (i) except that 48.5 g (0.102 mol) of methylglycerin was used. 45.6 g (0.0856 mol) of propylglycerin was obtained. yield
84.3%.

Mp ^{84~87 ℃ 1 H-NHR δppm (} CDCl 3, TMS reference) 0.7-2.4 (m, 43H) 2.63 (dd, 1H, J = 2.5,4.6Hz) 2.79 (t, 1H, J = 4.6Hz) 3.06 −3.20 (m, 2H) 3.37 (s, 3H) 3.45−3.95 (m, 7H) 5.34 (d, 1H, J = 5.0Hz) IR (ν: cm ⁻¹ ) 2938,1470,1383,1110,843 ( ii) 82.7 g (0.82 mol) of acetic anhydride and 0.82 g (0.0081 mol) of triethylamine are charged into a 300 ml reaction vessel equipped with a reflux condenser, a dropping funnel, a thermometer and a stirrer, and heated to 95 to 100 ° C. A solution obtained by dissolving 43.9 g (0.0826 mol) of the glycidyl ether obtained in Example 4 (i) in 40 g of acetic anhydride was dropped from the dropping roll over about 30 minutes while stirring at 95 ° C. After stirring was further continued at 100 to 120 ° C. for 6 hours, unreacted acetic anhydride was distilled off under reduced pressure. The resulting residue was purified by silica gel short column chromatography to give 1-0-cholesteryl-3-0-methyl-2-0.
47.7 g (0.0754 mol) of a crude product of -2 ', 3'-di-0-acetylpropylglycerin was obtained. Yield 91.2%. ¹ H-NMR δ ppm (CDCl ₃ , TMS standard) 0.7-2.4 (m, 43H) 2.06 (s, 3H) 2.08 (s, 3H) 3.08-3.20 (m, 1H) 3.35 (s, 3H) 3.40-3.78 ( m, 7H) 4.10-4.40 (m, 2H) 5.13-5.23 (m, 1H) 5.34 (d, 1H, J = 4.8Hz) IR (ν: cm ^-1 ) 2944,1644,1470,1374,1224,1110 (Iii) In a 500 ml flask equipped with a reflux condenser, a dropping funnel, a thermometer and a stirrer, 230 g of methanol and MeONa (28
% Methanol solution) and heated to 40 ° C., followed by 46.1 g (0.0728 mol) of the diacetate obtained in Example 4 (ii).
l) was added. After continuing stirring for about 1 hour, the mixture was extracted with a mixed solvent of ether and toluene. After washing with water, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel chromatography to obtain the desired 1-0-cholesteryl-3-0-methyl-2-0-2 ', 3'-dihydroxy. 31.1 g (0.0567 mol) of propylglycerin was obtained. Yield 77.9
%.

134-138 ° C ¹ H-NMR δppm (CDCl ₃ , TMS standard) 0.7-2.4 (m, 43H) 3.12-3.23 (m, 1H) 3.37 (s, 3H) 3.43-3.90 (m, 12H) 5.34 (d , 1H, J = 4.2 Hz) IR (ν: cm ⁻¹ ) 3424, 2938, 1470, 1383, 1107 Example 5 Vaseline / compound (Ia to Id) = 3/1 mixture (inventive product 1) and vaseline Was used to evaluate skin conductance and skin roughness by the following methods. Table 1 shows the results.

(Test method) 20- to 50-year-old woman with rough skin on her cheeks in winter 10
The subject is a subject, and different skin external preparations are applied to the left and right cheeks for two weeks. The following items were tested on the day after the two-week application was completed.

(1) Skin conductance After washing your face with warm water of 37 ° C, in a room with a temperature of 20 ° C and a humidity of 40%
After resting for 20 minutes, the water content of the stratum corneum was measured with a skin conductance meter (IBS). As the conductance value decreases, the skin becomes rough, and when the conductance value is 5 or less, the skin becomes rough. On the other hand, if this value is 20 or more, skin roughness is hardly recognized.

(2) Rough skin score Rough skin was observed with the naked eye, and judged according to the following criteria. Scores were shown as mean ± standard deviation.

Example 6 Using the compounds of the present invention (Ia to Id) obtained in Examples 1 to 4, skin external preparations (emulsified cosmetics) having the compositions shown in Table 2 below were produced, and their skin roughness improving effect was evaluated. 5 was evaluated in the same manner. Table 3 shows the results.

Claims (2)

(57) [Claims] 1. The following general formula (I) (In the formula, R ₁ is a saturated or unsaturated linear or branched hydrocarbon group or acyl group having 1 to 22 carbon atoms, or 2,3
-Represents a dihydroxypropyl group, R ₂ is a hydrogen atom or 2,
A glyceryl ether derivative of cholesterol or cholestanol represented by the formula: 2. An external preparation for skin containing the glyceryl ether derivative of cholesterol or cholestanol according to claim 1.