JPH0469314A - Skin cosmetic - Google Patents

Abstract

PURPOSE:To obtain a skin cosmetic having excellent moisture-retaining effect, useful for xeroderma and applicable in the form of lotion, milky lotion, cream, pack, etc., by using a specific phthalide derivative as an active component. CONSTITUTION:The objective skin cosmetic having moisture-retaining action and useful for xeroderma is produced by using a phthalide derivative of formula (R<1> is H, OH, methoxy, amino or dimethylamino; R<2> and R<3> are H or methoxy; R<4> is H, amino or dimethylamino; R<5> is H, 3-16C alkyl or 3-4C alkoxy) (e.g. 3-octylphthalide) as an active component. The phthalide derivative of formula may be natural substance or synthetic compound and can be extracted e.g. from a plant of family Umbelliferae. The phthalide derivative may be single substance or a combination of two or more compounds. The amount of the phthalide derivative is 0.1-10wt.% based on the total composition.

Description

[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to skin cosmetics, and more particularly, to skin cosmetics containing a specific phthalide derivative as an active ingredient, which has a moisturizing effect and is useful for dry skin. Regarding skin cosmetics.

[Prior art and problems to be solved by the invention] Conventionally, in order to maintain healthy skin, skin cosmetics have been made using hydrophilic skin moisturizers and oily skin softeners that provide appropriate moisture and oil content to the skin. It is being blended into

Skin moisturizers include glycerin, propylene glycol,
Polyethylene glycol, pyrrolidone carboxylate, etc. are used, but these may absorb water from the stratum corneum, the outermost layer of the skin, causing moisture loss in the skin, and they may also cause large amounts of water to be lost. However, skin cosmetics containing such substances have not always been satisfactory, such as giving an unpleasant feeling such as stickiness.

In addition, liquid paraffin, petrolatum, olive oil, squalane, lanolin, synthetic ester oil, etc. are used as skin softeners, but these are also included in skin cosmetics to the extent that they sufficiently prevent water evaporation from the epidermis. In some cases, they have the disadvantage of interfering with the normal metabolism of the skin.

Therefore, it has been desired to develop a drug that is pleasant to use, does not inhibit skin metabolism, and has a moisturizing effect on dry skin.

[A means of promise to solve problems]

Under these circumstances, the present inventors conducted intensive research on many compounds, and as a result, discovered that a phthalide derivative represented by the general formula (I) below has an excellent moisturizing effect, and completed the present invention.

That is, the present invention relates to the general formula (I) (wherein R1 represents a hydrogen atom, a hydroxyl group, a methoxy group, an amino group or a dimethylamino group, R2 and R3 represent a hydrogen atom or a methoxy group, R4 represents a hydrogen atom, Represents an amino group or a dimethylamino group, R5 is a hydrogen atom, and has 3 carbon atoms
~16 straight chain or branched alkyl group or 3 to 4 carbon atoms
The present invention provides a skin cosmetic material containing a phthalide derivative represented by the following (representing a straight chain or branched alkoxy group)

The phthalide derivative used in the present invention is represented by the general formula (N), where R5 is a direct alkyl group having 3 to 16 carbon atoms, such as propyl, butyl, pentyl, hexyl, heptyl, octyl, decyl, dodecyl,
Examples of branched alkyl groups include hexadecyl groups,
Examples include isopropyl, isobutyl, isoamyl, etc., and examples of straight chain or branched alkoxy groups having 3 to 4 carbon atoms include isopropoxy, propoxy, and butoxy groups.

These phthalide derivatives (1) may be either natural or synthetic; for example, in addition to those extracted from Apiaceae plants with an organic solvent such as ethanol or hot water, those synthesized by the following method may be used. I can do it.

(1) Reaction between phthalic anhydride derivative and acid anhydride (JP-A No. 63-83080) Ct+am,, 49.737 (1984), JP-A-Sho 6
3-83080, 6383081) CH3 (II) (In the formula, R1, R2, R3 and R4 have the same meanings as above, and R6 represents a straight chain or branched alkyl group having 2 to 15 carbon atoms) That is, a phthalic anhydride derivative and various acid anhydrides are heated and reacted to form an alkylidene phthalide derivative, and then water is added to the alkylidene phthalide derivative to form a phthalide derivative (n).
is obtained.

(2) Alkylation of benzoic acid derivatives at the 0-position (J, Or
g.

((n) (wherein R2, R3 and R4 have the same meanings as above,
(R7 represents a straight chain or branched alkyl group having 3 to 16 carbon atoms, and R8 represents an alkyl group.) That is, after reacting a benzoic acid amide derivative with a base such as butyllithium and reacting it with an aldehyde, Phthalide derivative (1) is obtained by hydrolysis.

(4) Reaction of phthalaldehydic acid and alkyl metal (I) (IV) (wherein R2, R3, R4 and R7 have the same meanings as above) That is, 4-methoxyphthalide derivative (III),
A phthalide derivative (IV) can be obtained by reacting with a Lewis acid such as boron tribromide or boron trifluoride.

In addition, a compound in which R1, R2, R3 and R4 are hydrogen atoms (for example, it can be synthesized by the following method (4) or (5)).

(In the formula, R9 represents a straight or branched alkyl group having 3 to 16 carbon atoms, and M represents a metal atom, metal halide, etc.) That is, phthalaldehydic acid and an alkyl metal such as a Grignard reagent are mixed under anhydrous conditions. By reacting, phthalide derivative (V) is obtained.

(5) Reaction between phthalaldehyde acid and alcohol (
(In the formula, RIG represents a linear or branched alkyl group having 3 to 4 carbon atoms.) That is, a phthalide derivative (Vl) is obtained by subjecting phthalaldehyde acid to a heating reaction with an alcohol.

These phthalide derivatives (I) can be used alone or in combination of two or more, and the total composition contains 0.1 to 10
It is preferable that the amount is blended in a range of % by weight. Blend amount is 0
．． If the amount is less than 1% by weight, the effect of the present invention will not be fully exhibited, and if it exceeds 10% by weight, no improvement in the effect commensurate with the increase can be expected.

The skin cosmetics of the present invention are prepared and used in various forms, such as lotions, milky lotions, creams, and packs.

In addition to the above-mentioned essential ingredients, the skin cosmetic of the present invention also contains pigments,
Arbitrary components such as fragrances, preservatives, surfactants, pigments, and antioxidants can be appropriately added within the range that does not impede the effects of the present invention.

〔Example〕

Next, the present invention will be further explained with reference to Reference Examples and Examples, but the present invention is not limited thereto.

Reference Example 1 Synthesis of 3-butylphthalide: Phthalic anhydride (60.0 g, 0.41 mol), valeric anhydride (79.3 g, 0.43 mol) and sodium acetate (21.0 g.

026moffi) is heated to 170°C,
The reaction progresses with the foaming of C02. After 7 hours, 41.7g of butylidenephthalide (0,22
mof>obtained. Yield 55%. Dissolve this butylidenephthalide in ethanol and 2.0 g of 5% palladium-carbon.
(5%) and hydrogenation is carried out at a hydrogen pressure of 40 at+n.

After 2 hours, remove the catalyst by filtration. 3-Butylphthalide was obtained by distillation under reduced pressure. Yield 55%.

b, p, 111-114℃/0.05mmHgH
NMR (270M)! 2. CDCN 3. TMS)
δ: 0.80-0.95 (3H, t, J=5.9Hz)
, 1.25-1.60(4)I,m), 1.65
-2.20 (2H, m), 5.45-5.50 (LH
, Q, J=4.0Hz), 7.45-7.9 (4H
, m) rR (NaC1, cm −' ) 3000 (s), 2950 (s), 2900 (m)
, 1780(s).

1640(m), 1490(m) Reference Example 2 Synthesis of 3-pentylphthalide: 3-pentylphthalide was obtained in the same manner as in Reference Example 1. Yield 29%.

'H-NMR (60MHz, CDC15, TMS)
δ: 8, 10-7.25 (4H, m), 5.45
(1)1. dd, J=4.0)1x.

6.0Hz), 2.30-1.10 (8H, m>,
0.80(3)1. t) Reference Example 3 Synthesis of 3-isoamyl phthalide: Isoamyl bromide (15.1 g, 1
00 mmol1), metal magnesium (2.2 g, 90
Isoamylmagnesium bromide was prepared from (mg atoms). In this Grignard solution, 0-phthalaldehyde acid (6.0 g, 4
0 mmof)/THF is gradually dropped. After aging under THF reflux for 2 hours and further at room temperature for 12 hours, hydrolysis and acid treatment were performed. Purification was performed by silica gel chromatography (hexane/ethyl acetate = 20/1) to obtain 3-isoamyl phthalide. Yield 38%.

' HNMR (270MHz, CD (j! 3.T
MS) δ: 0°8 (3H, d, J=2.9flz),
0.9 (:E, d, J=2.9Hz).

1.30-2.10 (5H, m), 5.5 (LH, d
d, J = 7.7Hz.

4,0Hz), 7.5-7.9 (4H,m)IR
(Nalj!, cm-')2950(s),
2900(+++), 1780(s), 1620(
w).

1491) (m) Reference Example 4 Synthesis of 3-octylphthalide: Using n-octyl bromide and n-octylmagnesium bromide prepared from metallic magnesium, 3-octylphthalide was synthesized in the same manner as in Reference Example 3. Obtained. Yield 38%.

H-NMR (60M)12. CDIJ,,TMS)
δ: 0.7-1.0 (3H, m>, 1.0-2.
3 (14H, m), IJ-2,1 (5t (, m),
5.3-5.6 (Ift, m), 7.2-8.
0(4t(,m) IR(NaC1,cm-') 2950(s), 2900(m), 1780(
s), 1620(w).

1480 (m> Reference Example 5 Synthesis of 3-hexylphthalide: 3-hexylphthalide was obtained in the same manner as in Reference Example 3. Yield 51%.

'84MR (200M)lz, CDCff13. T
MS) δ: 0.88 (3H, t, J = 6.49Hz),
2.2-1.1 (IOH, m).

5.47 (LH, dd, J=4.05tlz), 7.
44 (1ft, d.

J=7.4Hz), 7.52 (if, t,
J=7.34Hz), 7.67 (lH.

dt, J=1.01Hz, 7.4Hz), 7.
89 (IH, d, J=7.6Hz) IR (NaC1
, am -' ) 295(1(m), 2H(1(m), 1780(s
), 1620(w).

1480 (m), 1300 (m), 101070 (
Reference Example 6 Synthesis of 3-hebutylphthalide: In the same manner as in Reference Example 1, caprylic anhydride (71.4 g, 264 mm
of), phthalic anhydride (30.0g, 203mmo
f) Sodium acetate (12.5g, 152mm
After synthesizing 3-hebutylidenephthalide from ol),
Hydrogenation gave 3-hebutylphthalide. Yield 27%.

'H-NMR (60MHz, CDCf 3+ TM
S) δ: 8.0-7.2 (48, m), 5.6-5J
(IH, m), 2.3-17(2)1. m), 1
．． 7-1.0 (8ft, m), 1.0-0.7 (3
H, m) Reference Example 7 Synthesis of 3-decylphthalide 3-decylphthalide was synthesized in the same manner as in Reference Example 3.

Yield 35%.

m, p, 39.5-40.9℃' H-NMR (60MHz, [:DC13, TMS
) δ゛8.0-7.2 (4H, m), 5.6-5.2
(LH, m), 2.2-0.6 (21H, m) IR (KBr, am -') 2950 (s), 2900 (m), 1780 (s)
, 1620(w).

1490(m), 1[180(m) Reference Example 8 Synthesis of 3-dodecylphthalide: 3-dodecylphthalide was obtained in the same manner as in Reference Example 3. Yield 31%.

m, p, 52.8-53.3℃') I-NMR (60MHz, CDIJ!s,
TMS) δ: 8.0-7.2 (4H, m), 5.6-
5.2 (LH, m), 2.0-0.7 (25H, m) IR (Br, cm-') 2980 (s), 2900 (m), 1780 (s
), 1630(w).

1620(w), 1480(m), 1080(
+n) Reference Example 9 Synthesis of 3-hexadecyl phthalide': Odoriferous hexadecylmagnesium was prepared from hexadecyl bromide and metallic magnesium, and 3-hexadecyl phthalide was prepared in the same manner as in Reference Example 3.
Hexadecyl phthalide' was obtained. Revenue = 15.4%.

'H-NMR (270MHz, CDCf 3+
TMS) δ Near, 91 (LH, d, J=7
．． 69Hz), 7.69-7.51 (2H, m).

7.45 (01, d, J=6.59Hz), 5.51
-5.48 (LH, m).

2.04-1.76 (LH, m), 1.57-0.9
2 (28H, m).

0,90 (3H,t, J=6.22Hz)IR(K
Br, cm -') 2950 (s), 2900 (m), 1770 (s)
, 163Q(w).

1490 (m), 11l100 (Reference Example 103-Synthesis of isopropoxyphthalide 20-7
Taraldehyde acid (6.0 g, 40 mmof), isopropyl alcohol (4.8 g, 80.0 mmol)
) was reacted at 100°C for 6 hours to obtain 3-isopropoxyphthalide. Yield 75.0%.

m, p, 65.3-66.7℃ 'H-NMR (60MHz, CDC1, TMS) δ:
1.3(3fl,d,J=6.0Hz), 1.4(
3H, d, J = 6.0Hz).

4, 2 (LH, qu, J=6.0Hz), 6.
4 (LH, s), 7.4-8.0 (4H, m) IR (KBr, Cm-') 3000 (m>, 2950 (m>, 1770 (s))
, 1620(w).

1480 (m), 1360 (m), 130
0 (m) Reference Example 11 Synthesis of 3-propoxyphthalide: 3-propoxyphthalide was obtained in the same manner as in Reference Example 10 except that propyl alcohol was used instead of isopropyl alcohol. Yield 72%.

'H-NMR (60MHz, CDCf 3+ TM
S) δ: 0.9(3t(, t, J=7.01(z),
11 (2H, q, J=7.0Hz).

4, 0-3.6 (2H, m), 6.3 (IH,
s), 8.0-7.3 (4H, m) IR (KBr, cm -') 3000 (+n), 2950 (m), 2900
(m), 1780(s).

1630(w), 1480(m), 1300(
m), 101080 (Reference Example 12 Synthesis of 3-butoxyphthalide: 3-butoxyphthalide was obtained in the same manner as in Reference Example 1O, except that butyl alcohol was used instead of isopropyl alcohol. Yield: 87%.

84MR (270M) Iz, CD (13, TMS) δ
:? , 86(1)1. d, J=8.06Hz), 7.
70 (IH, d.

J=733Hz), 7.61-7.57 (2H, m)
, 3.93-3.77 (2H, m), 1.69-1
．． 61 (2N, m), 1.45-1.37 (2H,
m), 0.93 (3H, t, J = 7.33 tlz) Reference Example 13 Synthesis of 4-methoxy-3-butylphthalide: Dry THF 40 mE, n-butyl lithium/n-beef san 14 mf (22,0 mmol), Tetramethylethylenediamine (2.56g, 22.0mmol)
Mix and cool to -68 °C aL,N,N-diethyl-3-
Methoxybenzoic acid amide (4.15g, 20.0mm
on)/THF was gradually added and after 30 minutes, white crystals were obtained. Magnesium bromide ether' (11,0g
, 42.6 mmof was added and reacted, and then 1-pentanal (3.5 g, 40.0 mmof) was added to -78
The reaction was carried out at ℃. After acid hydrolysis and chloroform extraction, 4-methquine-3-butylphthalide was obtained by vacuum distillation. Yield 22%.

m, p, 44.3-45.3℃ LNMR (270MHz, CDCl 3.7M5) δ
:0.89 (3H, t, J=6.96Hz), 1.5
-1.2 (4H, m).

1.8-1.6 (LH, m), 2.35-2.20 (
IH, m), 5.5 (IH, cld, J・7,69
flz, 2.93Hz), 7.09(IH, t, I'
4.4Hz), 75-7.4(2H,m)IR(KB
r, cm -') 3000 (m>, 2960 (m), 2900 (w>
, 1780(s).

1630(m), 1520(m), 1300(s)
, 1060(s) Reference Example 14 Synthesis of 4-methoxy-3-hebutylphthalide: m-anisic acid (
15.2g, 100+nmof) and thionyl chloride (3
m-anisyl chloride was obtained from 6.3 g, 305ITIITlO1). 2-amino-2-methyl-1-propatol (17.8 g.

200a+noA') was reacted with this m-anisyl chloride, and further treated with thionyl chloride to obtain 2-(3methoxyphenyl)-4,4-dimethyloxazoline hydrochloride. Next, n-butyllithium/n-hexane (1,
Further, octanal (7.7 g, 60 mmol) was added, and after the reaction, the reaction product was treated in 6 N HCl at 120 °C to obtain 4-methoxy-3-hebutylphthalide. . Yield 48%.

111, P, 63.9-64.5℃'H-NMR (
60MHz, CDIj! s, TMS) δ: 1.0-0.
6 (3H, m), 2J-1,0 (12H, m>, 3
．． 9(3)1゜m), 5.6-5.3(LH,m),
7.1 (lft, t, J=4Hz).

7.5 (2H, J=4flz) IR (Br, cm-') 2950 (m), 2900 (w), 1780 (s)
, 1640(iv).

1520 (m), 1300 (S), 1060 (Il
+) Reference Example 15 Synthesis of 4-methoxy-3-decylphthalide: 4-methoxy-3-decylphthalide was obtained in the same manner as in Reference Example 14. Yield 99.3%.

m, p, 57.8-60.7℃'H-NMR (200MHz, CDCff1s,
TMS) δ: 0, 88 (3) 1. t, J=6.2
)1z), 1.54.1 (18fl, 01).

5.55(1)1. dd, J=3.1flz, 7.8H
z>, 7.00 (IH, d.

J=7.7Hz), 7.37(1N, t, J=7
．． 6flz), 7.47 (IH.

d, J=7.1)1z) IR (KBr, cm-') 2950 (m), 2900 (w), 1790 (s)
, 1640(w).

1520(s), 1500(s), 1295(s)
, 101060 (Reference Example 16 Synthesis of 4-hydroxy-3-butylphthalide: Under nitrogen gas atmosphere, 4-methoxy-3-butylphthalide synthesized in Reference Example 13 and boron tribromide/methylene chloride (
9mi! , IN), 4-hydroxy-3
-Butylphthalide was obtained. Yield 63%.

m, p, 162.5-164℃ H-NMR (60M) Iz, CDC1j+ TMS)
δ: 0.9 (3t(, t, J=5flz), 2.3-
1.2 (6H, m), 2.9 (IH, bs), 5.
6(1)1. dd, J=8.4Hz), 7.5-7.
1 (3H, m) IR (KBr, Cm −' ) 3240 (br), 2980 (w>, 2880 (w),
1730(s).

1620(m), 1510(m), 1480(
m), 1300 (m).

1100 (w) Reference Example 17 Synthesis of 4-hydroquine-3-heptyl phthalide: Using 4-methoxy-3-hebutylphthalide synthesized in Reference Example 14 and boron tribromide, 4 was synthesized in the same manner as in Reference Example 16.
-Hydroxy-3-heptyl phthalide was obtained. Yield 74
%.

'l(-NMR(60MHz, C0Cf 3.7M
5) δ: 0.9 (3H, t, J=5Hz), 2.3-
1.2 (6H, m), 2.8 (LH, bs), 5.
6-5.3 (LH, m), 7.5-7.0 (3H, m
) IR (KBr, Cm-') 3250 (br), 2980 (w), 2950 (m
), 2900 (m).

1740(s), 1630(m), 1480(m)
, 1300(s).

1110(m) Reference Example 18 Synthesis of 4- and droxy-3-decylphthalide: Using 4-methoxy-3-decylphthalide synthesized in Reference Example 15 and boron tribromide, 4- was synthesized in the same manner as in Reference Example 16.
Hydroxy-3-denruphthalide was obtained. Yield 62%.

m, p, 155.6-157.1tIR (KBr
9cm-') 3250 (br), 2950 (m), 2900h)
, 1740 (s>.

1640(m), 1500(m), 1310(m)
, 1120 (m) Example 1 Measurement of skin conductance value: 20 subjects with dry skin (age 20-27) were
The participants were divided into groups, and 10 people each applied the present invention product 1 or comparative product 1 having the composition shown in Table 1 to the left forearm, and left the left forearm uncoated. The test period was three days in winter, and the test substance was applied twice a day in the morning and evening.

The day after the 3-day application was completed, the left and right forearms were washed with soap, and 2 hours after washing, a high-frequency impedance meter (IB) was used.
The skin conductance value of the applied area was measured using Model IB-400 (manufactured by S Company). The results are shown in Table 1.

In addition, the skin conductance value was shown as the average value of the relative value when the skin conductance value of the uncoated area was set as 100.

As is clear from the results in Table 1, product 1 of the present invention has a higher skin conductance value than comparative product 1, and has an excellent moisturizing effect on dry skin.

Margins below [Effects of the Invention] The skin cosmetic of the present invention has an excellent moisturizing effect and is useful for dry skin.

that's all Applicant Hanao Kaisha Ltd.

Claims (1)

[Claims] 1. General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (In the formula, R^1 represents a hydrogen atom, a hydroxyl group, a methoxy group, an amino group, or a dimethylamino group. , R^2 and R^3 represent a hydrogen atom or a methoxy group, R^4 represents a hydrogen atom, an amino group or a dimethylamino group, and R^5 represents a hydrogen atom, a linear or branched chain having 3 to 16 carbon atoms. A skin cosmetic containing a phthalide derivative represented by: