KR20010010473A - A Process For Preparing Phytosphingosine Aqueous Solution - Google Patents

Abstract

PURPOSE: A method for producing an aqueous solution of phytosphingosine is provided, thereby the higher concentration of phytosphingosine can be dissolved in a solution, so that phytosphingosine is applied to aqueous cosmetics and medicines. CONSTITUTION: A method for producing the aqueous solution of phytosphingosine comprises the steps of: adding the phytosphingosine powder into the distilled water and heating the solution to 60 to 90deg.C with agitation; neutralizing pH of the solution by adding lactic acid with agitation; and adding the extract of bark of willow tree to prevent the recrystallization of phytosphingosine, in which the amount of the added phytosphingosine powder is 0.1 to 10 wt.%, preferably 0.5 to 6 wt.%, lactic acid is added in an amount of 0.2 to 4g per 1g of phytosphingosine, and the added extract of bark of willow tree contains 10 wt.% of salicylic acid and salicin.

Description

A process for preparing phytosphingosine aqueous solution

The present invention relates to a method for producing a transparent aqueous solution by dissolving phytosphingosine by at least 5% and as much as 10% using water without using any solvent such as alcohol.

More specifically, phytosphingosine is added to distilled water at a concentration of about 5% by weight to 10% by weight, followed by stirring while warming the temperature to about 80 ° C. while neutralizing the pH using various acids including lactic acid. After dissolving phytosphingosine and completely dissolving phytosphingosine, 0.1 to 1% by weight of willow bark extract containing 10% by weight or more of salicylic acid-like substances such as salicylin and salicylic acid was added. To prepare a solution of phytosphingosine solution phase.

Phytosphingosine, a type of sphingolipid, is one of the major cell membrane components of a living body, and is a bioactive substance having various biological functions as a signal transduction agent of a signal transduction system (Okazaki et al. , 1989; Kim et al., 1991). All sphingolipids of the living body are based on sphingoid long chain bases called sphingosine, phytosphingosine and sphinginine, and ceramides having fatty acids linked to amino groups of sphingolipid bases.

Sphingolipids have been shown to play a key role in life phenomena, such as the regulation of cell growth, proliferation, differentiation, and induction of apoptosis through a newly discovered signal transduction process called the "sphingomyelin cycle" (Hannun, 1994, 1996; Hannun and Obeid, 1995) TNF-α, IL-1, γ-IFN, and FAS ligands have been found to be involved. Sphingolipids occupy most of the skin lipids and maintain the skin's moisturizing properties and regenerate the skin's protective film, while at the same time serving as the skin's primary defense against attack from microorganisms. In addition, sphingolipids are involved in the inhibition and activation of protein kinase C, regulation of EGF receptor activity, induction of cellular Ca ⁺⁺ ions, and regulation of Rb and NF-κB genes. It is widely used for anticancer research. Recently, most skin diseases, including atopic dermatitis, in which 3-4% of the world's population is patients, have been found to be caused by the low content of various sphingolipids in skin lipids. It is expected that it can be used as a next-generation pharmaceutical ingredient that can replace antibiotics and anti-inflammatory steroid hormones.

Ceramides III and VI, which have phytosphingosine and phytosphingosine as the backbone, have been widely used in the cosmetic industry as a major functional ingredient (Cosmeceutical) for the past several years. For example, ceramides (N-acylated sphingosine) and N-acylated phytosphingosine, which account for more than 40% by weight of skin lipids, are used for skin moisturizing function and regeneration of damaged skin barrier. Due to its excellent efficacy, it is used worldwide for skin care cosmetics, and its use has been extended to hair products.Phytosphingosine, along with ceramide, began to be used as a functional raw material such as moisturizers and anti-aging agents in the cosmetics industry. Compared to ceramides, skin regeneration, antibacterial and anti-inflammatory effects are excellent, and the use is rapidly increasing.In the pharmaceutical industry, atopic dermatitis, acne, wound treatment, etc. are already under review, and phytosphingosine is a core material of functional cosmetics. Industrial anti-aging products, moisturizing products, regeneration of damaged skin It is expected to expand its use in products and atopic dermatitis, acne treatment, psoriasis and skin itching treatment, wound healing, etc.

However, sphingolipids, which were extracted from animals, are hard to use any longer due to mad cow disease, etc., and methods of manufacturing using pure synthetic methods are too expensive and economically difficult to use. In addition, the sphingolipids present in the human body are often different from the stereochemical structure, and it is difficult to obtain sphingolipids having a constant stereochemical structure. Phytosphingosine has recently been developed through a yeast fermentation method called Pichia cifera, and can be easily obtained. Phytosphingosine obtained through fermentation of yeast has been found to have stereochemically the same structure as that existing in the human body, and many industries It has started to be used in the market and its usage is increasing rapidly. However, due to the problem of solubility of phytosphingosine, which can be obtained in large quantities through yeast fermentation, there was a limit to use in cosmetics and pharmaceuticals. Moreover, phytosphingosine is not soluble in water at all and is only dissolved in about 1% by weight in solvents such as isocetyl alcohol, which can be used as a raw material for cosmetics. There is a difficulty and it is not used at all in the clear solution products such as skin cosmetics.

The concentration of phytosphingosine currently used in cosmetics is about 0.1 to 0.3% by weight, but it is difficult to achieve the desired effect sufficiently in this amount. Phytosphingosine should be used at least 0.5% by weight in order to have sufficient effect. As a result, a method for dissolving phytosphingosine at a high concentration must be developed to obtain an optimal effect by using it in cosmetics and pharmaceuticals.

Thus, the present inventors have carefully examined the above problems and through a long study of the heart, using water, lactic acid, and willow bark extract without using any solvent such as alcohol, the phytosphingosine at least 2% by weight, as much as 10% The solution was dissolved up to% to obtain a clear solution of phytosphingosine solution.

The high concentration of phytosphingosine aqueous solution prepared by the method of the present invention has a function of antimicrobial, anti-inflammatory, skin regeneration, etc. that phytosphingosine has a high concentration of aqueous solution, so it can be applied to various cosmetics at a high concentration up to 1 to 2% by weight, Compared to the conventional method used by dissolving phytosphingosine using a solvent or the like, it is possible to greatly solve the inconvenience in use. In addition, the compatibility has been greatly improved, so that it can be easily applied to water-soluble cosmetics such as skins, essences, water-soluble pack products, body essences, etc., which have not been used at all until now, and can greatly contribute to improving the function of water-soluble cosmetics. Phytosphingosine in aqueous solution is much more convenient than powder products even when applied to existing cream products, and has the advantage of being easily applied to skin care cosmetics.

Hereinafter, the present invention will be described in detail.

The present invention completely dissolves phytosphingosine by at least 5% by weight and as much as 10% by weight using water, lactic acid and willow bark extract without using any solvent such as isocetyl alcohol. The present invention provides a method for preparing an aqueous solution of phytosphingosine in a transparent state.

More specifically, the phytosphingosine powder is added to distilled water at a concentration of 0.1% to 10% by weight, more preferably at a concentration of 0.5% to 6% by weight, and then the temperature is raised to about 80 ° C. Stir for 40 minutes. Subsequently, while slowly dropping lactic acid, the solution is stirred for 30 to 40 minutes while the pH of the solution is neutralized until the phytosphingosine is completely dissolved. The lactic acid is preferably added within the range of 0.2 to 4 g per gram of phytosphingosine. The phytosphingosine powder used phytosphingosine, which is commercially available from Doosan Corporation under the product name of DS-Phytosphingosine, was used as a raw material.

The phytosine dissolution temperature is preferably dissolved within the range of 60 ~ 90 ℃, the dissolution time depends on the phytosphingosine concentration, but most preferably dissolved for 30 to 50 minutes stirring. When the phytosphingosine is completely dissolved, the willow bark extract (Brookley, USA WILLOW BARK Extract) containing about 10% by weight of salicylic acid and salicyline is gradually added under stirring at a concentration of 0.1 to 10% by weight of the solution. High concentration phytosphingosine aqueous solution can be obtained. Willow bark aqueous solution used in the present invention was used Willow Bark Extract (Billow Bark Extract) sold by Brook Co., Ltd. in the United States.

When phytosphingosine was dissolved using only acid such as lactic acid, low-temperature storage and recrystallization proceeded over time, whereas when phytosphingosine was dissolved using lactic acid and willow bark extract at the same time, low-temperature storage and In spite of the prolonged passage of time, it remained in aqueous solution or in a clear gel without any change.

To obtain a clear liquid high concentration of phytosphingosine solution, 0.1 to 10% by weight of the willow extract is added within the range of 0.5 to 3% by weight of phytosphingosine, and 2 to 10% by weight of the willow extract is added within the range of 5 to 10% by weight of phytosphingosine. It is preferable. When the willow extract is added to the phytosphingosine solution at a concentration of 2% by weight or less, the phytosphingosine solution is recrystallized and cannot be used in the product. The addition of more than 10% by weight of the willow extract has a disadvantage in that the viscosity of the phytosphingosine aqueous solution is greatly increased and the aqueous solution hardens itself. have.

Example 1 Preparation of Aqueous Phytosphingosine Solution

0.1 wt% of phytosphingosine powder was added to 100 ml of distilled water, followed by stirring at 70 rpm while the temperature was gradually raised to about 82 ° C. Under stirring, 0.2 g of lactic acid is added to dissolve phytosphingosine while neutralizing the pH. After visually confirming that the phytosphingosine was completely dissolved after stirring for 30 minutes, 2% by weight of the willow bark extract was added dropwise while maintaining the stirring to obtain an aqueous solution of phytosphingosine having a slightly opaque color viscosity.

Example 2

0.5 wt% of phytosphingosine powder is added to 100 ml of distilled water, and the temperature is slowly stirred at 80 rpm while gradually raising the temperature to about 82 ° C. Under stirring, 0.5 g of lactic acid is added to dissolve phytosphingosine while neutralizing the pH. After visually confirming that phytosphingosine was completely dissolved after stirring for 30 minutes, 1% by weight of the willow bark extract was slowly added dropwise while stirring to form a clear solution of phytosphingosine solution.

Example 3

5 wt% of phytosphingosine powder was added to 100 ml of distilled water, followed by stirring at 95 rpm while the temperature was gradually raised to about 80 ° C. Under stirring, 6 g of lactic acid is added to dissolve phytosphingosine while neutralizing the pH. After visually confirming that phytosphingosine was completely dissolved after stirring for 35 minutes, 2% by weight of the willow bark extract was slowly added dropwise while stirring to produce a clear solution of phytosphingosine solution.

[Test Example 1] Viscosity test of phytosphingosine aqueous solution

100 ml of distilled water was added to eight 300 ml four-necked flasks, and the phytosphingosine concentration was 0.1%, 0.5%, 1%, 3%, 5%, 6%, 8%, and 10% by weight, respectively. After the addition, the temperature is stirred while heating to about 80 ° C. To this is dissolved phytosphingosine under stirring while adding lactic acid at a rate of 0.2 to 0.5 g per gram of phytosphingosine. After visually confirming that phytosphingosine was completely dissolved, the willow bark extract was increased to a concentration of 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, and 10% by weight. While checking the viscosity of the aqueous solution of phytosphingosine (Table 1)

The viscosity of the phytosphingosine aqueous solution increased as the concentrations of phytosphingosine and willow extract increased to form a highly viscous gel, but the phytosphingosine aqueous phase was most stable at 3 to 6% by weight of phytosphingosine and 0.1 to 3% by weight of willow extract. Maintained.

Test Example 2 Transparency Experiment of Phytosphingosine Aqueous Solution

By adding the phytosphingosine to the concentration of 0.1% by weight, 0.5% by weight, 1% by weight, 3% by weight, 5% by weight, 6% by weight, 8% by weight, 10% by weight in the same manner as in Test Example 1 Stir while warming the temperature to about 80 ℃. To this is dissolved phytosphingosine under stirring while adding lactic acid at a rate of 0.2 to 0.5 g per gram of phytosphingosine. After visually confirming that the phytosphingosine was completely dissolved, the willow bark extract was increased to a concentration of 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, and 10% by weight. The transparency of the aqueous solution of phytosphingosine was investigated (Table 2).

The transparency of the aqueous solution of phytosphingosine was increased, and there was a test section in which recrystallization occurred, but when the willow extract was added to 0.1 to 3% by weight of phytosphingosine, and 2 to 10% by weight of the willow extract was added to 5 to 10% by weight of phytosphingosine. In one case it remained in a clear liquid state.

Test Example 3 Antibacterial Effect of Phytosphingosine Aqueous Solution

After distilled water was added to 100 ml of a four-necked flask, phytosphingosine was added thereto at a concentration of 5% by weight, followed by stirring while warming the temperature to about 80 ° C. Hereto, 2.8 g of lactic acid is slowly added dropwise to dissolve phytosphingosine under stirring. After visually confirming that the phytosphingosine was completely dissolved, the willow bark extract was added at a concentration of 1% by weight to obtain a clear liquid phytosphingosine solution.

In order to measure the efficacy of the 5% by weight aqueous solution of phytosphingosine (containing 1% by weight of bark bark extract), the microbial inhibitory effect was measured (see Table 3 and Table 4 below). As a test strain, Staphylococcus aureus, a kind of skin microorganisms, and Propionibacterium acnes, a cause of acne, were used. After diluting the test strain with the buffer solution to about 3,000-4,000 cells per cc, phytosphingosine was added at concentrations of 100 μg / cc, 10 μg / cc, 1 μg / cc, and 0.1 μg / cc, respectively, for 1 hour at 37 ° C. After standing, the cells were plated in agar medium and cultured for 24 hours, and the number of colonies was measured.

As a comparative example, a 5% by weight aqueous solution of phytosphingosine without adding willow extract and phytosphingosine dissolved in alcohol were used.

* Comparative Example 1: 5 wt% aqueous solution of phytosphingosine (dissolved with cetyl alcohol)

Comparative Example 2: 5 wt% aqueous solution of phytosphingosine

(Soluble in lactic acid, willow extract not added)

Comparative Example 3: Willow Extract

The present invention: 5% by weight aqueous solution of phytosphingosine (1% by weight of willow extract)

* Comparative Example 1: Phytosphingosine 5% by weight aqueous solution (dissolved with cetyl alcohol)

Comparative Example 2: 5 wt% aqueous solution of phytosphingosine

(Soluble in lactic acid, willow extract not added)

Comparative Example 3: Willow Extract

The present invention: 5% by weight aqueous solution of phytosphingosine (1% by weight of willow extract)

As can be seen in Table 3 and Table 4, the aqueous solution of phytosphingosine according to the present invention is compared with the comparative examples, Staphylococcus aureus, which is a skin microorganism, and propionibacterium acnes, which is the causative agent of acne. It can be confirmed that the antibacterial effect is excellent in the back.

Test Example 4 Inhibitory Effect of Phytosphingosine Cosmetic Cream on Skin Microorganisms

In order to observe the inhibitory effect on the skin microorganisms of the 5% by weight aqueous solution of phytosphingosine (containing 1% by weight of bark bark extract) prepared in Test Example 3, a cosmetic cream was prepared using the aqueous solution of phytosphingosine and then the facial skin After spreading on the skin, the distribution of skin supernatant microorganisms was observed (see Table 5 below). For the cosmetic cream, 2.5 g of glyceride, 2.5 g of cholesterol, 1.5 g of stearic acid, 3.5 g of ceramide, 1.5 g of oleic acid and 1.5 hydrated lecithin 1.5 After adding g and completely dissolving, 100 ml of phytosphingosine 5% aqueous solution was added to prepare a cosmetic cream. After applying the cosmetic cream on one face of nine subjects, the distribution of microorganisms on both sides of the face was examined after 2 hours.

As can be seen from Table 5, it can be seen that the skin of the subject subjected to the application of the aqueous solution of phytosphingosine according to the present invention is significantly reduced in the skin microorganisms than the site where the cream is not applied.

The high concentration of phytosphingosine aqueous solution prepared by the method of the present invention has a function of antimicrobial, anti-inflammatory, skin regeneration, etc. that phytosphingosine has a high concentration of aqueous solution, so it can be used in various cosmetics in high concentration up to 1 to 2% by weight, such as solvent By using the phytosphingosine was dissolved separately compared to the conventional method used was able to greatly eliminate the inconvenience in use. In addition, it can be applied to water-soluble cosmetics such as skins, essences, water-soluble pack products, body essences, etc. that have not been used at all until now can greatly contribute to the improvement of the function of water-soluble cosmetics. Phytosphingosine in aqueous solution is much more convenient than powder products even when applied to existing cream products, and has the advantage of being easily applied to skin care cosmetics.

Claims (8)

Adding phytosphingosine powder to distilled water at a predetermined concentration to warm and stir at 60 to 90 ° C; adding and stirring a predetermined lactic acid to dissolve the phytosphingosine powder while neutralizing the pH; And Method for producing a phytosphingosine aqueous solution, characterized in that the step consisting of adding a predetermined willow bark extract to prevent recrystallization The method of claim 1, wherein the phytosphingosine powder is added to distilled water in an amount of 0.1 wt% to 10 wt%, preferably 0.5 wt% to 6 wt%. The method of claim 1, wherein the lactic acid is a method for producing an aqueous phytosphingosine solution, characterized in that the addition of 0.2 to 4g per gram of phytosphingosine. According to claim 1, Willow bark extract is added to prevent recrystallization is characterized in that willow bark extract containing about 10% by weight of salicylic acid (Salicylic Acid) and salicylic acid (Salicin) Method for producing an aqueous phytosphingosine solution. The method of claim 1, wherein the willow bark extract is added to the aqueous solution of phytosphingosine at a concentration of 0.2 to 10% by weight. A method of using the phytosphingosine aqueous solution prepared according to any one of claims 1 to 5 in cosmetics such as cosmetic creams, essences, water-soluble packs, skins, body essences, etc. The method of claim 6, wherein the phytosphingosine aqueous solution added to the cosmetic is characterized in that the use of 0.1 to 10% by weight aqueous solution The method of claim 7, wherein the phytosphingosine aqueous solution is used in cosmetics at a concentration of 0.1 to 5% by weight.