KR0181103B1 - Ceramic type compounds and method for the preparation thereof - Google Patents

Abstract

The present invention has the properties of natural ceramides, and relates to a novel ceramide-type compound represented by the following Chemical Formula 1 and a preparation method thereof.

[Formula 1]

(Wherein R is a saturated or unsaturated aliphatic chain having 10 to 22 carbon atoms)

When applied to the skin, the ceramide-like compound of Formula 1 shows strong affinity to the stratum corneum, the surface of the skin and the outer layer of the skin, densifies their structure to increase water retention, and at the same time promotes the alteration of the stratum corneum to improve dry skin. Or it can be used as an active active substance to keep the skin in a healthy state, and provides excellent effects such as preventing skin aging and imparting wettability, flexibility and elasticity to the skin.

Description

Ceramide-like compound and preparation method thereof

The present invention has the properties of natural ceramides, and relates to a novel ceramide-type compound represented by the following Chemical Formula 1 and a preparation method thereof.

[Formula 1]

(Wherein R is a saturated or unsaturated aliphatic chain having 10 to 22 carbon atoms)

In order for an individual to continue its life activities, it is necessary to have a protective film that protects harmful substances and microorganisms from the external environment from penetrating the surface of skin tissue and at the same time maintains moisture. It is the stratum corneum that plays this role in man. In other words, the barrier function of the skin against the evaporation of water from inside the skin and the permeability of various substances is performed by the stratum corneum.

The stratum corneum is keratinocytes (Keratinocytes) division, migration, differentiation, and finally peeled off the surface. Of the substances that make up the stratum corneum, keratinocyte interstitial lipids form a layered structure of molecular aggregates and contribute greatly to maintaining healthy and beautiful skin. The keratinocyte interstitial lipid having water retention function, barrier function, keratinocyte adhesion function and the like is composed of ceramide, glycolipid, cholesterol, cholesterol ester, free fatty acid and the like. The main active ingredient is ceramide, which is known to play a central role in water retention and barrier function of the stratum corneum. Ceramide compounds found in the stratum corneum of humans include sphingosine of formula 2 or phytosphingosine of formula 3, as shown in the following formulas (4) to (10).

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

[Formula 7]

[Formula 8]

[Formula 9]

[Formula 10]

However, as aging of the skin progresses with age, the content of ceramide in the stratum corneum decreases, which decreases the binding force of the keratinocytes to the skin surface and eventually the stratum corneum is not protected. That is, as the content of ceramide in the stratum corneum decreases, the skin surface becomes rough due to loss of skin moisture, exposure to external stimuli such as ultraviolet rays or chemicals, and peeling of keratinocytes.

When the stratum corneum is damaged by skin aging or external stimulation, and the content of ceramide in the stratum corneum decreases, it has been reported that supplementation of ceramide from the outside can restore the lamellar structure of the skin and restore the skin to a normal state. It is also reported that the lamellar structure of the skin surface is not formed of ceramide alone but is formed when other lipids present in the stratum corneum, for example, fatty acids or cholesterol coexist.

As a result of these studies, a search for natural flora and fauna and microorganisms has been conducted for the purpose of supplementing ceramide from the outside, and various flora and fauna containing ceramides have been identified. However, the ceramides present in these plants and microorganisms are extremely small, and it is practically difficult to extract and use these lipids in large amounts for the enhancement of the stratum corneum and its application to skin protection cosmetics, and the production cost is high. In addition to these problems, natural ceramides have very low solubility in various solvents, cosmetics, and raw materials used in cleaning products, so that only a small amount of natural ceramides can be used to manufacture these products. There are disadvantages.

Thus, the present inventors have studied the molecular structure of the ceramide derived from nature in order to provide a ceramide compound by synthesis, and as a result, two long-chain alkyl groups, amide groups in the main chain and a plurality of hydroxyl groups which are structural features of the ceramide derived from nature As a result of molecular design, the new compound of formula (1) has a structure similar to that of natural ceramide, so that it is easy to form a lamellar lamellar structure. It was confirmed that the recovery of the damaged skin and the skin protection effect is increased, and completed the present invention.

Accordingly, it is an object of the present invention to provide a ceramide-like compound represented by formula (1).

Another object of the present invention is to provide a method for preparing a ceramide-like compound represented by the formula (1).

Another object of the present invention to provide a base cosmetic composition containing a ceramide-like compound represented by the formula (1) in an amount of 0.001 to 20% by weight relative to the total weight of the composition.

Method for producing a novel ceramide-like compound represented by the formula (1) provided in the present invention,

(1) dissolving an aliphatic amine in ethanol and then reacting with glycidol to obtain an aliphatic amine derivative having a glycidyl group represented by Formula 11 below

[Formula 11]

(Wherein R is a saturated or unsaturated aliphatic chain having 10 to 22 carbon atoms);

(2) mixing the aliphatic amine derivative obtained in step (1) and 2-dodecen-1-yl-succinic acid (2-dodecen-1-yl succinic anhydride) and reacting at high temperature to produce an amide compound step; And

(3) purifying by column separation of the amide compound prepared in step (2)

Characterized in that it comprises a.

In the present invention, the aliphatic amine in step (1) is an amine having a saturated or unsaturated chain having 10 to 22 carbon atoms, for example decylamine, undecylamine, dodecylamine, tridecylamine, tetradecylamine, hexa It is decylamine, octadecylamine, oleylamine, docosylamine, etc., and the amine which has a C14-18 linear alkyl group is more preferable. Step (1) The reaction is preferably carried out at a molar ratio of 1 to 2 moles of glycidol with respect to 1 mole of aliphatic amine. When the content of glycidol is less than 1 mole relative to 1 mole of the aliphatic amine, the yield decreases, and when the molar excess exceeds 2 moles, many by-products are produced.

In addition, although the reaction of step (1) is possible at 0 to 80 ° C., the reaction rate is slower than 15 ° C., and when the temperature exceeds 40 ° C., the tertiary amine added with 2 moles of glycidol is mainly produced. ~ 40 ℃ is good. The secondary amine thus produced is obtained by removing the solvent after completion of the reaction and recrystallization from ethanol.

The novel ceramide-like compound of formula (1) of the present invention is produced by vigorously stirring the intermediate of formula (11) obtained in the step (1) reaction with anhydrous 2-dodecen-1-yl-succinic acid at high temperature for 3 to 6 hours. After the completion of the reaction, the solvent is distilled off to remove the solvent, and then column separation is performed to obtain the desired compound of formula 1.

In addition, although the reaction of step (2) is possible at 10 to 80 ° C., the reaction rate is slower than 20 ° C., and when by-products are generated when it exceeds 50 ° C., 20 to 50 ° C. is preferable.

The ceramide-like compound of formula (1) prepared by the above-mentioned manufacturing method shows strong affinity to the stratum corneum, which is the surface of the skin and the outer layer of the skin when applied to the skin, densifies their structure to increase the water retention function, and at the same time It can be used as an effective active material for improving dry skin by promoting the alteration or to keep the skin in a healthy state, and can provide excellent effects such as preventing skin aging and imparting wettability, flexibility and elasticity to the skin.

Therefore, the ceramide-like compound represented by Formula 1 having the above-described effect may be formulated as an external skin preparation such as a base cosmetic, and may be in the range of 0.001 to 20% by weight, preferably 0.1 to 10% by weight, based on the total weight of the composition It can be used in combination suitably according to the formulation in the inside. The composition containing the ceramide-like compound according to the present invention is not particularly limited in its formulation as an external preparation for skin, specifically, softening longevity, astringent longevity, nourishing longevity, nourishing cream, massage cream, essence, eye essence, eye cream, It may be formulated into a cleansing cream, cleansing foam, cleansing water, pack or powder.

Hereinafter, the method for preparing a ceramide-like compound and the composition containing the same according to the present invention will be described in more detail with reference to Examples and Test Examples. However, the present invention is not limited to these examples.

Example 1 Preparation of N-hexadecylamino-1,2-propanediol

In a 1 L round flask, 48.2 g of hexadecylamine was dissolved in 700 ml of ethanol. 16 ml of glycidol was slowly added thereto at 30 ° C. After stirring for 3 hours at the same temperature, it was left overnight. The resulting solid was filtered and recrystallized in ethanol to give 54 g of N-hexadecylamino-1,2-propanediol (yield: 85%). The target compound was confirmed from the analysis results of Table 1.

Example 2 Preparation of N-oleylamino-1,2-propanediol

In Example 1 53.5g of oleylamine was added instead of hexadecylamine and treated in the same manner as in Example 1 to obtain 53g of white powder. From the analysis results of Table 1, the target compound, N-oleylamino-1,2-propanediol was confirmed. (Yield: 78%)

Example 3 Preparation of N-octadecylamino-1,2-propanediol:

In Example 1 53.9g of octadecylamine instead of hexadecylamine was added and treated in the same manner as in Example 1 to obtain a white powder 57g. From the analysis results in Table 1, the target compound, N-octadecylamino-1,2-propanediol was confirmed. (Yield: 85%)

Example 4 Preparation of (N-hexadecyl-N-2,3-dihydroxypropyl) -3- (2-dodecen-1-yl) carboxamidopropionic acid

To a 250 ml flask, 15.8 g of N-hexadecylamino-1,2-propanediol prepared in Example 1 and 14.6 g of anhydrous 2-dodecen-1-yl-succinic acid were added to 120 ml of chloroform and warmed to 40 ° C. Dissolved. After stirring for 4 hours at the same temperature, the solvent was distilled off under reduced pressure. The residue was separated by silica gel column to give 18.5 g (yield: 61%) of a pale yellow solid. From the analysis results of Table 1, (N-hexadecyl-N-2,3-dihydroxypropyl) -3- (2-dodecen-1-yl) carboxamidopropionic acid as the target compound was confirmed.

Example 5 Preparation of (N-oleyl-N-2,3-dihydroxypropyl) -3- (2-dodecen-1-yl) carboxamidopropionic acid

17 g of N-oleylamino-1,2-propanediol prepared in Example 2 and 14.6 g of 2-dodecen-1-yl-succinic anhydride were treated in the same manner as in Example 4 to obtain 18.5 g of a pale yellow solid. (Yield 61%) was obtained. From the analysis results of Table 1, (N-oleyl-N-2,3-dihydroxypropyl) -3- (2-dodecen-1-yl) carboxamidopropionic acid was identified as a target compound.

Example 6 Preparation of (N-octadecyl-N-2,3-dihydroxypropyl) -3- (2-dodecen-1-yl) carboxamidopropionic acid

17.2 g of N-octadecylamino-1,2-propanediol prepared in Example 3 and 14.6 g of 2-dodecen-1-yl-succinic anhydride were treated in the same manner as in Example 4 to obtain a pale yellow solid 17.8 g (yield: 59%) was obtained. From the analysis results in Table 1, (N-octadecyl-N-2,3-dihydroxypropyl) -3- (2-dodecen-1-yl) carboxamidopropionic acid as the target compound was confirmed.

Example 7 Preparation

In Example 1, 42.6 g of tetradecylamine was added instead of hexadecylamine and treated in the same manner as in Example 1, to obtain 51 g of N-tetradecylamino-1,2-propanediol.

17 g of N-tetradecylamino-1,2-propanediol and 14.6 g of 2-dodecen-1-yl-succinic anhydride prepared in the same manner as in Example 4 were treated to give 16.4 g of a pale yellow solid (yield: 59%). It was confirmed that it is a target compound from the analysis result of Table 1.

Table 1

Structural analysis data

When preparing a cosmetic containing the ceramide-like compound of the present invention in an amount of 0.001 to 20% by weight, preferably 0.1 to 10% by weight, it was confirmed that a lamellar structure was formed on the stratum corneum of the skin to increase the moisturizing and softening effect. .

Test Example 1 Comparison of Solubility of Natural Ceramides and Ceramide-like Compounds

Of the six kinds of natural ceramides represented by the formulas (4) to (10), the cosmetics are mainly used in the type 3 of formula (6), and in this test, the natural ceramide (from the bovine brain) of the formula (3) and the ceramide-like compound of the present invention. The solubility in solvents such as ethanol, which is mainly used in cosmetics, was compared. The sample was dissolved in a solvent at 80 ° C. and then cooled to 20 ° C. The results are shown in Table 2.

[Table 2]

Comparison of solubility of natural ceramides and ceramide-like compounds (w / w%, 20 ° C)

In the case of Type 3 of Formula 6, which is a natural ceramide, when a 0.5% solution was prepared, it became a gel-like suspension with no flowability in all solvents.

(Formulation Examples 1-4 and Comparative Examples 1-2)

In the following prescription, the aqueous phase and the oil phase were heated, dissolved, mixed, stirred, and cooled to room temperature to prepare a cream.

Test Example 2 Skin Safety Test

Skin safety was compared with respect to the cream cosmetics prepared in Formulation Examples 1 to 4 and Comparative Examples 1 and 2.

As for the safety of the skin, a normal patch test was conducted. Dividing the 60 people into six groups, the creams prepared in Formulation Examples 1-4 and Comparative Examples 1-2 were divided into groups and used for 10 days on the face. The average value was calculated. The results are shown in Table 3 below.

(Score)

4: very irritating and not suitable for use as a cosmetic

3: It is recommended to not use because of severe irritation

2: Slightly irritating and need attention when using

1: almost no irritation

0: No irritation at all, can be used for sensitive skin

Table 3

From the results in Table 3, there is no significant difference between each sample and there is little irritation can be evaluated that the novel ceramide-like compound of the present invention is suitable for use as a raw material for cosmetics.

Test Example 3 Recovery of Damaged Skin

The skin recovery effects of the cream cosmetics prepared in Formulation Examples 1 to 4 and Comparative Examples 1 and 2 were compared.

The recovery effect of the skin was measured by dividing 30 hairless Guinea Pigs into six groups and the creams prepared in Formulation Examples 1 to 4 and Comparative Examples 1 and 2 in each group. The test method was as follows.

Using a Fin chamber, 2.5% SDS (sodium dodecyl sulfate) was patched in the flanks of test animals for 30 minutes to cause irritation, and then 200 μl of test substance was applied to each patch. The stimulus induction and recovery were assessed by measuring the Transepidermal Water Loss (TEWL) through the stratum corneum using an evaporimeter. Instrument measurements were taken at 30 minutes, 1 hour, 2 hours, 4 hours, 7 hours, and 24 hours before patching the SDS. The results are shown in Table 4 below.

Table 4

Skin Recovery Test Result Unit: AU

As shown in Formulation Examples 1 to 4 in the results of Table 4, the cream added with the new ceramide-like compound showed a remarkable recovery ability of the damaged skin as compared to the cream without addition, and showed a recovery ability similar to that of natural ceramide. In particular, the C16 fatty acid (palmitic acid, Formulation Example 1) derivative was most prominent.

Test Example 4 Defense Test

The protective effects of the cream cosmetics prepared in Formulation Examples 1 to 4 and Comparative Examples 1 and 2 were compared.

The protective effect was measured by dividing 30 hairless Guinea Pigs into six groups and dividing the creams prepared in Formulation Examples 1 to 4 and Comparative Examples 1 and 2 into each group. The test method was as follows.

The test material was applied to the side of the test animal once a day for 7 days, and then patched for 30 minutes with 2.5% SDS using a pin chamber to determine the degree of irritation induced. The induced stimulus was measured using an evaporation meter, and the measurement was performed immediately before the patch, 1 hour after the patch was removed, and 24 hours. The results are shown in Table 5 below.

Table 5

Skin Defense Test Result Unit: AU

Hereinafter, based on the results of the above test example, by containing a ceramide-like compound of formula (1) to propose a basic cosmetic composition of various formulations that can provide an excellent effect of protecting the skin from external stimulation without skin irritation. However, the composition of the present invention is not limited to the following formulation example.

Formulation Example 5 Flexible Cosmetics

Formulation Example 6 Nutritional Longevity

Formulation Example 7 Nutrition Cream

Formulation Example 8 Essence

Formulation Example 9 Cleansing Foam

(Formulation Example 10) Pack

As can be seen in the above examples and test examples, the ceramide-like compound of formula (1) provided by the present invention is a substance having an excellent effect of repairing damaged skin and protecting the skin from external stimuli. In addition, it can be used as an effective substance for the recovery and prevention of skin damaged by external environmental changes, and can provide an excellent effect on increasing the elasticity of the skin and preventing and improving skin aging. Limited in content when formulated in may be used.

Claims (5)

New ceramide-like compound represented by the following formula (1). [Formula 1] (Wherein R is a saturated or unsaturated aliphatic chain having 10 to 22 carbon atoms) (1) dissolving an aliphatic amine in ethanol and then reacting with glycidol to obtain an aliphatic amine derivative having a glycidyl group represented by Formula 11 below [Formula 11] (Wherein R is a saturated or unsaturated aliphatic chain having 10 to 22 carbon atoms); (2) mixing the aliphatic amine derivative obtained in step (1) and 2-dodecen-1-yl-succinic acid (2-dodecen-1-yl succinic anhydride) and reacting at high temperature to produce an amide compound step; And (3) purifying by column separation of the amide compound prepared in step (2) A method for producing a ceramide-like compound represented by the formula (1) according to claim 1, comprising a. The method according to claim 2, wherein the step (1) is performed at 15 to 40 ° C, and the step (2) is performed at 20 to 50 ° C. The basic cosmetic composition, which comprises a ceramide-like compound represented by the formula (1) according to claim 1 in an amount of 0.001 to 20% by weight based on the total weight of the composition. The cosmetic according to claim 4, wherein the basic cosmetic has a formulation of softening cream, converging cream, nourishing cream, nourishing cream, massage cream, essence, eye essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack or powder. Basic cosmetic composition.