JPH05310552A - Skin external preparation - Google Patents

Abstract

PURPOSE:To obtain a skin external preparation by containing a 1,2-diphthanoyl- glycerol derivative and an active substance to further enhance the effect of the active substance. CONSTITUTION:The objective skin external preparation contains at least one of compounds of formula I (X is formula II to VI), e.g. 1,2-diphthanoyl-glycero-3- phosphocholine, an antiinflammatory agent, antihistamic agent, therapeutic agent for psoriasis, therapeutic agent for wound, ultraviolet ray absorbing agent, therapeutic agent for scar, chapped skin improver, blood circulation promotor, a component for stimulating cells, ingredient having beautifying action, etc. The compound of formula I and the active ingredients are each blended in an amount of 0.01-20wt.%, preferably 0.1-10wt.%.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an external preparation for skin characterized by containing a 1,2-diphytanoyl-glycerol derivative and an active substance. More specifically, the effect of the contained active substance is further enhanced. It relates to a skin external preparation.

[0002]

BACKGROUND OF THE INVENTION Generally, a drug containing an active substance is administered to a living body by oral administration or parenteral administration such as injection. In recent years, these administration methods have been replaced. The method of transdermal administration has also been studied. However, in the case of transdermal administration, due to the barrier function of the stratum corneum of the skin, the absorbed amount of the drug is small and a sufficient medicinal effect cannot be expected.

Further, there is also known an external preparation for the skin in which liposomes, which are usually used, are made to coexist in order to improve the drug effect (JP-A-60-15).
No. 2410), but the improvement effect is not sufficient.

[0004] Therefore, as a result of earnest studies on the skin external preparation for further enhancing the effect of the contained active substance, the present inventors have found that the skin external preparation containing the 1,2-diphytanoyl-glycerol derivative and the active substance. However, they found that the effect of the contained active substance was remarkably improved, and completed the present invention.

[0005]

The present invention provides the following general formula (A):

[Chemical 2] The external preparation for skin is characterized by containing at least one of the 1,2-diphytanoyl-glycerol derivative represented by and an active substance.

Among the 1,2-diphytanoyl-glycerol derivatives represented by the above general formula used in the present invention, 1,2-diphytanoyl-glycero-3-phosphocholine is a known substance and can be chemically synthesized. can get. (WR Redwood et al., Biochim.Biophys.Act
a., 233, 1-6 (1971)] It can also be obtained by induction from phospholipid obtained from egg yolk or the like. In addition, 1,2-diphytanoyl-glycero-3-phosphoethanolamine,
1,2-diphytanoyl-glycero-3-phosphoserine, 1,2-diphytanoyl-glycero-3-phosphoinositol, 1,2-diphytanoyl-glycero-3-
The phosphate or its salt can be obtained in the same manner as the above compound. Examples of the salt include sodium salt, potassium salt, ammonium salt, and alkanolamine salt.

The content of the 1,2-diphytanoyl-glycerol derivative is preferably 0.01 to 20.0% by weight, more preferably 0.1 to 10% by weight, based on the total amount of the formulation components of the external preparation of the present invention. It is 0.0% by weight. If the blending amount is less than 0.01% by weight, the effect aimed at by the present invention is not sufficient. On the other hand, if it exceeds 20.0% by weight, the improvement of the effect commensurate with the increase cannot be expected.

The active substance used in the present invention is water-soluble,
Any substance may be used as long as it can be used as a skin external preparation regardless of its fat solubility. For example, anti-inflammatory agent, antihistamine, psoriasis therapeutic agent, wound healing agent, ultraviolet absorber, anti-acne agent, rough skin improving agent, blood circulation promoting component, cell activating component, whitening component, etc. Is an example.

The components having a blood circulation promoting and / or cell activating action include the conventionally used cembly extract, ginseng extract, vitamin E and vitamin E derivative,
Diisopropylamine dichloroacetate, γ-aminobutyric acid, D-pantothenyl ethyl ether, D-pantothenyl ethyl alcohol, placenta extract, ceramide and ceramide derivatives, γ-linolenic acid, linoleic acid, aloe extract, mucopolysaccharide, biotin , Γ-oryzanol is at least one selected from the group consisting of:

Here, among each of the above-mentioned components, there are those individually specified as a blood circulation promoting agent or a cell activating agent, and a combination of the action and effect of the blood circulation promoting agent and the cell activating agent. However, any of them can be used in the present invention.

The component having a whitening effect is at least one selected from the group consisting of ascorbic acid derivative, hydroquinone derivative, pyrones, bovine placenta extract and serum deproteinized protein which have been conventionally used.

The amount of these active substances to be added to the external preparation for skin of the present invention is appropriately adjusted depending on the action and effect or the dosage form of the external preparation, but based on the total amount of the prescription components of the external preparation, 0.01 to 20% by weight is preferable,
More preferably, it is within the range of 0.1 to 10% by weight.
If the amount is less than 0.01% by weight, it is difficult to obtain the effect, and if the amount exceeds 20% by weight, the effect is not improved correspondingly.

The external preparation for skin of the present invention is obtained by uniformly dispersing a 1,2-diphytanoyl-glycerol derivative and the above-mentioned active substance in a polyhydric alcohol such as glycerin, 1,3-butylene glycol and dipropylene glycol. It is prepared by adding this to an aqueous phase component in a skin external preparation base such as cream, emulsion, lotion, etc., followed by ultrasonic irradiation, and then treatments such as emulsification, dispersion, dissolution and solubilization.

In addition to the above, the external preparation for skin of the present invention may be appropriately blended with a coloring fragrance, a preservative, a surfactant, a pigment, an antioxidant, etc. within the range to achieve the object of the present invention. You can

[0015]

EXAMPLES The present invention will be described in detail below based on examples and comparative examples. The following tests were conducted to evaluate the effect of each active ingredient. Rough skin improving effect test Skin blood flow test (blood circulation promoting effect) Stratum corneum turnover speed measurement (cell activating effect) Skin color brightness recovery test (whitening effect) Each test method is as follows.

Test method for improving rough skin effect The lower leg of 20 middle-aged and elderly subjects complaining of rough skin, dry skin, and senile dry skin symptoms was tested for the effect of continuous application for 4 weeks. About 1 g of the sample was applied to the left lower leg test site of the test subject once a day, and the condition of the skin before and after the start of the test was evaluated according to the following criteria. The lower right leg was not coated with the sample and served as a control. Criteria for skin dryness −: Normal ±: Minor dryness, no desquamation +: Dry, mild desquamation ++: Dry, moderate desquamation +++: Dryness, remarkable desquamation Compare the determination results of the test site before and after the test and the control site, When skin dryness is improved by two or more stages (for example, + →
−, ++ → ±) is valid, 1 is a little better when improved, and invalid when there is no change. The test results were shown by the number of subjects who were valid or slightly valid.

Skin Blood Flow Test Method 3 New Zealand White rabbits were shaved on the abdomen,
After being fasted for 18 hours, pentaparbitol sodium salt is intravenously injected at a rate of 35 mg / kg for anesthesia. A plate-type transducer was fixed on the sample application site (test site) on the abdomen with cellophane tape, and a cross thermoelectric skin-type skin blood flow meter (Shin-Ai Inc.
Skin blood flow (μV) is measured using a 01 type). The sample was uniformly applied to a 3 × 2 cm skin site in an amount of 0.1 g, and the blood flow rate (CB) before the sample application and a certain time after the sample application (for example, 0.5, 1.0, or 2.0 hours). Blood flow rate (Ct) of (after) is measured, and blood flow rate of increase (%) is calculated by the following formula.
To calculate. The test results are shown by the average value of the blood flow increase rate of 3 birds. Blood flow increase rate (%) = (Ct−CB) / CB × 100

Measurement method of stratum corneum turnover speed An ointment was prepared by adding 5% by weight of fluorescent dye dansyl chloride to white vaseline, and applied to the skin of the forearm of a subject.
Apply occluded for a time and permeate dansyl chloride into the stratum corneum. After that, apply the test sample to the same site twice a day (morning and evening) and examine the fluorescence of dansyl chloride every day.
The number of days until the fluorescence disappeared was defined as the turnover rate of the stratum corneum of the skin. When cells are activated, their growth rate increases and turnover increases.

Skin color lightness recovery test method The back skin of 20 subjects was irradiated with ultraviolet rays in the UV-B region at twice the minimum erythema dose, and the reference lightness of each skin was set by setting a sample application site and a non-application site. (Vo value, Vo 'value) was measured. Then, apply the sample to the application site twice a day 3 times.
After continuous application for a month, the skin lightness (Vn value, Vn 'value) of the application site and the non-application site after 3, 8 and 13 weeks was measured, and the skin color recovery evaluation was carried out according to the criteria of Table 1. .. The lightness of skin (V value of Munsell color system) was calculated from X, Y, and Z values obtained by measurement with a high-speed spectrocolorimeter.
The evaluation was shown by the average value of the evaluation points of 20 subjects after 13 weeks.

[0020]

[Table 1]

Examples 1 to 7 and Comparative Examples 1 to 6 (Cream) (1) Composition A cream was prepared according to the composition shown in Table 2.

[0022]

[Table 2]

(2) Preparation method The 1,2-diphytanoyl-glycerol derivative and the active substance are uniformly dispersed in glycerin, which is then added to purified water.
Add 0 wt% and sonicate to obtain (B).
(A) and (C) are uniformly dissolved at 80 ° C., respectively, and (A)
(C) is added to and emulsified and dispersed, and then (B) at 50 ° C.
And cooled to 30 ° C. to prepare.

(3) Characteristics Table 3 shows the results of various tests carried out on each cream.

[Table 3]

As shown in Table 3, Comparative Examples 1 to 3 containing the active substance alone, Comparative Example 4 containing the 1,2-diphytanoyl-glycerol derivative alone, Comparative Example 5 containing neither of them, and the activity The cream of Comparative Example 6 in which the substance and the conventional phospholipid were mixed did not have a sufficient effect on various properties. On the other hand, Examples 1 to 1 of the present invention
The cream of 7 showed remarkable effects in various properties,
It showed a significant improvement in the effect of the active substance.

Examples 8 to 13 and Comparative Examples 7 to 12 (Lotion) (1) Composition Lotions were prepared according to the compositions shown in Table 4.

[0027]

[Table 4]

(2) Preparation method Dipropylene glycol was added to 1,2-diphytanoyl-
Glycerol derivative and active substance are evenly dispersed, added to 10.0% by weight of purified water, and sonicated,
Obtain (B). (A) and (C) are mixed and dissolved at room temperature, (C) is added to (A), and (B) is further added,
Prepare by stirring.

(3) Characteristics Table 5 shows the results of various tests performed on each lotion. As shown in Table 5, Comparative Examples 7 to 9 in which the active substance was blended alone, Comparative Example 10 in which the 1,2-diphytanoyl-glycerol derivative was blended alone, Comparative Example 11 in which neither was blended, Active substance and the conventional The lotion of Comparative Example 12 containing the above phospholipid did not have a sufficient effect on various properties. On the other hand, Example 8 of the present invention
The lotion No. 13 showed remarkable effects on various properties, showing a significant improvement in the effect of the active substance.

[0030]

[Table 5]

[0031]

As described above, the external preparation for skin of the present invention is
It is clear that the incorporation of the 1,2-diphytanoyl-glycerol derivative and the active substance markedly increases the effect of the incorporated active substance.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location A61K 9/107 R 7329-4C 47/24 E 7433-4C

Claims (1)

[Claims] 1. The following general formula (A): An external preparation for skin comprising at least one of the 1,2-diphytanoyl-glycerol derivative represented by and an active substance.