JPWO2007145276A1 - Cosmetics containing high-purity sphingomyelin liposome - Google Patents

Abstract

By increasing the amount of ceramide in the skin, the barrier ability and moisture retention of the skin are improved, and a technique for helping to improve rough skin and wrinkles is provided. Embodiments of the present invention include making liposomes using very high purity sphingomyelin and blending it into cosmetics. By nano-forming sphingomyelin, sphingomyelin can be penetrated deep into the skin, thereby improving the barrier ability and moisture retention of the stratum corneum, resulting in the effects of improving rough skin and alleviating atopic symptoms. [Selection] Figure 1

Description

  The present invention relates to a technique for improving rough skin, spots, wrinkles, skin aging, atopic dermatitis and the like.

  The skin is the largest organ that covers the living body and consists of the epidermis, dermis and subcutaneous tissue. The epidermis is the basal layer, spiny layer and granule layer consisting of living cysts (mainly keratinocytes) and the keratinocytes finish the final keratinization and become dead cysts (corneocytes) Divided into layered stratum corneum. The stratum corneum is filled with stratum corneum lipids between horny cysts, forming the largest parier of substance permeation from the skin. The stratum corneum lipid is derived from lamellar granules, and its composition is 50% sphingolipid, 20% cholesterol ester, 10% cholesterol, 20% fatty acid, and 95% of the sphingolipid is ceramide. These lipids form a network of hydrogen bonds with water molecules between the stratum corneum, and are also involved in moisture retention (moisturization) by building a lamellar structure containing water molecules in the form of layers in the structural unit. It is believed that disturbances in these lipid contents in the stratum corneum cause dry skin (so-called rough skin) and several skin diseases. For example, in atopic dermatitis, sphingolipids in the stratum corneum, especially ceramide, are significantly reduced. In general, ceramide tends to decrease with age, and is deeply related to spots, wrinkles, skin aging, atopic dermatitis and the like.

  Recent progress in lipid research reveals that ceramide is involved not only in the ability to form barriers but also in the maintenance of skin structure through intercellular communication such as apoptosis and differentiation of cells Has been.

  In recent years, biosynthesis and metabolic pathways of sphingophospholipids have been clarified, and it has been suggested that sphingophospholipids and their metabolic lipids are involved in cell survival and proliferation. Sphingomyelin in which phosphocholine is bonded to the 1-position hydroxyl group of ceramide is hydrolyzed by sphingomyelinase to become ceramide and phosphocholine. Lipid synthesis and metabolism in the epidermis is highly active and is thought to be largely independent of the systemic circulatory system, so if sphingomyelin can penetrate deep into the skin, This may affect the ceramide content in the gap and the amount of ceramide synthesis in keratinocytes below the stratum corneum. If the content of ceramide in the stratum corneum is changed, it will greatly affect the barrier ability and moisture retention of the skin. However, this phenomenon has not been clarified so far.

  Japanese Patent Application Laid-Open No. 63-211208 describes cosmetics containing sphingomyelin. The cosmetics disclosed in this document are said to have excellent skin permeability of the active ingredient, activate skin cell functions when applied to the skin, and exhibit remarkable effects on skin protection and beautification. (Page 2, upper right column, lines 4-18). However, this document does not describe whether sphingomyelin can be penetrated deep into the skin when the cosmetic according to this document is applied to the skin, and the amount of ceramide synthesis in the skin is not described. Whether it changes or not is not described.

WO97 / 30696 describes liposomes containing sphingomyelin as the main component of membrane constituent lipids. The liposome is used to stably hold a drug (claims 1 to 3, summary). However, WO 97/30696 does not mention cosmetics at all, nor does it mention ceramide biosynthesis at all.
Japanese Patent Laid-Open No. 63-211208 WO97 / 30696 publication

  Under such a background, the present invention provides a technique that improves the barrier ability and moisture retention of the skin by increasing the amount of ceramide in the skin, and contributes to the improvement of rough skin and atopic dermatitis. is there.

  One of the features of the present invention is that the sphingomyelin penetrates deep into the skin by making the sphingomyelin nano. The idea itself for blending sphingomyelin into cosmetics has existed for a long time, and such an idea has already been described in JP-A-63-211208 as described above. However, the present invention is characterized in that sphingomyelin is nano-sized and blended into cosmetics. The nano-characteristic feature allows sphingomyelin to penetrate deep into the skin, which increases the ceramide content in the skin, particularly in the stratum corneum.

  The increase in ceramide is expected to have various effects on skin and hair improvement. Ceramide has an excellent barrier forming ability and biocompatibility, and has a remarkable moisturizing effect. Therefore, by applying the nano-sized sphingomyelin according to the present invention, effects of improving rough skin and improving moisture retention can be expected.

  Furthermore, the increase in ceramide not only improves the barrier-forming ability but also improves the barrier maintenance ability, thus greatly contributing to the maintenance of skin homeostasis. Therefore, improvement of dry skin can be expected by repeatedly applying the nanonized sphingomyelin according to the present invention.

  Ceramide is a main component in the cell membrane complex of not only skin but also hair, and its composition is reported to be ceramide II (88%) and ceramide V (12%). Ceramide is also known to have a lamellar structure stabilizing effect. Therefore, when the nano-sized sphingomyelin according to the present invention is applied to hair or scalp cells, it can be expected to improve cuticles of damaged hair and improve tensile strength.

  According to Akio Ohdera's “Anti-aging ingredient with ceramide production promoting effect and anti-wrinkle ingredient with synergistic effect of ceramide and maolicaine” (Fragrance Journal, November 2004 issue) The dry skin caused by atopic dermatitis, aging, etc. is deeply related to quantitative and qualitative disturbances of various ceramides.According to recent research, ceramide is a skin damage caused by UV. It has been found that keratinocytes activate sphingomyelinase and produce intercellular ceramide when UVB is irradiated to the skin, which acts as a second messenger, Stops differentiation and growth, and apoptosis of keratinocytes begins. And so, in that. Ceramide type II, which helps to protect the skin by promoting the status of the cells damaged by UV is particularly are deeply involved in this process. "It found.

  As shown from the experimental results described later, the amount of ceramide type II in the skin is increased by applying the nanonized sphingomyelin according to the present invention. For this reason, it can be expected that certain embodiments of the present invention can contribute to the repair of skin and hair cells damaged by UV.

  The present invention can be expected to contribute to the improvement of atopic dermatitis. According to the Ministry of Health and Welfare Research on Psychosomatic Disorders, atopic dermatitis is “chronic eczema lesions that occur mainly in predisposing factors for atopy”, but a decrease in the amount of ceramide in the stratum corneum is atopic dermatitis Therefore, increasing the amount of ceramide in the stratum corneum is effective in improving atopic dermatitis. By applying the nanonized sphingomyelin according to the present invention, the amount of ceramide in the skin is increased, so improvement of atopic symptoms can be expected.

  As can be understood from these, the present invention is a cosmetic for improving rough skin and dry skin, a cosmetic and external preparation for repairing skin damaged by ultraviolet rays, and alleviation and improvement of atopic symptoms. It can be implemented as various cosmetics and external preparations for the purpose of improving the skin and hair, such as cosmetics and external preparations for cosmetics, cosmetics for improving hair cuticles and hair quality.

  In a preferred embodiment of the present invention, a method of converting sphingomyelin into a liposome is adopted as a method of nano-forming sphingomyelin. As is well known, liposomes have a diameter of about 100 nm to 1 μm and can penetrate the skin barrier to reach the dermis. Therefore, the inventor decided to infiltrate sphingomyelin deep into the skin by making liposomes of high-purity sphingomyelin.

  In a preferred embodiment of the present invention, a high-purity sphingomyelin in the form of liposomes is used. In the most preferred embodiment, the liposomes are comprised of phospholipids that are 98% or more sphingomyelin.

  As far as the present inventor knows, cosmetics using such high-purity sphingomyelin liposomes are not known before the filing date of the present application. In addition, no one has conceived of using sphingomyelin liposomes to increase the amount of ceramide synthesis in the skin, thereby improving the rough skin and alleviating atopic symptoms. Therefore, the embodiment of the present invention includes various forms of cosmetics and external preparations.

  Next, one of the embodiments of the present invention will be introduced together with data showing the effect.

[Nanoification of sphingomyelin]
As a raw material of sphingomyelin to be nano-sized, for example, “COATSOME (registered trademark) NM-70” “COATSOME (registered trademark) NM-10” “sphingomyelin nature (trademark)” manufactured by Nippon Oil & Fats Co., Ltd. can be used . These raw materials are sphingomyelin with a purity of 98%. By making this high-purity sphingomyelin into a liposome, nano-sized sphingomyelin can be obtained. The method for producing liposomes is described on page 5 of the above-mentioned Non-Patent Document 2, which is incorporated herein by reference.

[Application of sphingomyelin liposome]
1 mL of 1% sphingomyelin liposome was applied for 6 hours under culture in a maintenance medium, and then the sphingomyelin liposome formulation was removed from the application site. Then, it culture | cultivated for 12 hours or 24 hours using the keratinization promotion medium. In order to compare with the application of sphingomyelin liposomes, pH 7.4 PBS was used as a control.

[Liquid extract]
Transfer the cultured skin peeled off with a knife from Transwell ™ to a 10 mL Spitz tube, add 6 mL of chloroform / methanol mixture (1: 1), and probe type ultrasonic device (SONIFIER ™ B-12 , Branson sonic power company) at 60W for 5 minutes. Thereafter, the obtained solution was filtered with 0.2 μm Millex ™ -GN (Millipore corporation, Bedford, MA, USA), and the collected filtrate was dried with nitrogen at 50 ° C. to obtain lipid components in the skin. Got. 200 μL of chloroform / methanol mixture (1: 1) was added to these and the lipid components were dissolved again to prepare HPTLC (High Performance Thin Layer Chromatography, thin plate for high resolution and high sensitivity detection) samples. .

[Development / Coloring]
A sample for HPTLC was plotted and developed using chloroform: methanol: acetic acid (190: 9: 1) as a developing solvent. After the development, the color was developed using 10% copper sulfate 8% nitric acid aqueous solution. After coloring, HPTLC was read with a scanner and analyzed using Image J (http://rsb.info.nih.gov/ij/).

〔result〕
FIG. 1 shows the results when the sphingomyelin liposome preparation was applied for 6 hours and cultured for 12 hours. FIG. 2 shows the results when the sphingomyelin liposome preparation was applied for 6 hours and cultured for 24 hours. In both cases, two sphingomyelin liposome application examples, two control examples, and two ceramide II-only HPTLCs were observed side by side.

  It can be seen that in both the case of the culture time of 12 hours (FIG. 1) and the case of 24 hours (FIG. 2), the band near the ceramide II is deeper when the sphingomyelin liposome preparation is applied compared to the control. . From this, it was confirmed that the application of the sphingomyelin liposome preparation increased ceramide II or lipid having a similar structure. Moreover, when FIG.1 and FIG.2 is observed, when a sphingomyelin liposome formulation is applied, it is recognized that the oleic acid is increasing. Since oleic acid is made from ceramide, an increase in oleic acid may also indicate an increase in ceramide.

  Next, another embodiment of the present invention will be introduced together with data showing its effect. In Example 2, a cosmetic containing 0.1% of a 1% sphingomyelin liposome aqueous solution was applied to three people suffering from atopic skin disease, and the course was observed.

[Subject 1: HC]
Age: 38 years old, gender: female, occupation: elementary school teacher. Despite mild atopic disease, dermatitis was observed almost throughout the body, and itching was felt throughout the body.
In normal life, lotions and creams were applied to affected areas after face washing or bathing (at least twice a day) in the morning and evening, and changes were observed.
The result showed that itching healed in a short time, and in the following month, almost all the rough skin was improved.

[Subject 2: MM]
Age: 25 years old, gender: female, occupation: part-time. Suffers from mild atopic disease. The affected part of the neck muscle is prominent.
Lotion and cream were applied to the affected area after washing the face in the morning and evening or after bathing (at least twice a day) in the normal life as with HC, and changes were observed.
The results showed that itching was reduced when lotion was applied to the affected area, and the atopy-like disease found in the neck was cured in about one month.

[Subject 3: KH]
Age: 27 years old, gender: female, occupation: office worker (pharmacy working). Suffers from atopic dermatitis throughout the body. The skin color is dark and itchy.
Lotion and cream were applied to the affected area after washing the face in the morning and evening or after bathing (at least twice a day) in the normal life as with HC, and changes were observed. In the case of KH, the number of times of application per day was determined when itching was felt, and there was no limit.
As a result, the skin darkening faded within six months, and the skin of the ruggedness improved as the healthy person approached the skin.

  As described above, the embodiment of the present invention has been described by introducing test examples that prove the effect. However, the embodiment of the present invention is not limited to the embodiment described here, and is within the scope of the idea of the present invention. It should be noted that various embodiments can be taken. For example, an appropriate active ingredient can be encapsulated in the sphingomyelin liposome according to the present invention.

  More specifically, the cosmetic according to the embodiment of the present invention can be, for example, the following cosmetics: funny, face powder, paper funny, cream funny, solid funny, powder funny, kneaded funny, water Interesting, cosmetics for skin, lotion, skin lotion, soft lotion, astringent lotion, mucous lotion, hand lotion, shaving lotion, medicated lotion, lotion, moisturizer, cosmetic, cream, oily cream , Medium oil cream, Weak oil cream, Cleansing cream, Cold cream, Hizenic cream, Vanishing cream, Hand cream, Shaving cream, Bleaching cream, Foundation cream, Medicated cream, Lip cream, Milky lotion, Skin lotion, Skin milk Burn cream, sunscreen cream , Sunburn (for), sunscreen (for), finishing cosmetics, foundation, face color, concealer, makeup base, makeup base, pre-makeup, red, lipstick, lipstick, ripple rouge, lip color, lip Pencil, Lip Gloss, Lip Liner, Eye Makeup, Eye Shadow, Eye Color, Eye Liner, Eyebrow, Eyebrow Pencil, Eyebrow Brush, Mascara, Eyelash Cosmetic, Nerima, Cheek Cosmetic, Blusher, Cheek Color, Cheek Loose, Body Makeup, Hairdressing, Hair Nourishing, Scalp, Hair Coloring, Hair Washing, Hair Cosmetics, Hair Oil, Color Rinse, Cold Perm Solution, Suki Oil, Setting Lotion, Hair Dye, Hair Decoloring Agent, Chick, Permanent liquid, bottle oil, hair cream, hair spray Hair tonic, hair fixer, hair lacquer, hair rinse, balum, pomade, body powder, talcum powder, bath powder, perfume powder, baby powder, natural nail powder, bath cosmetic, bath oil, bath salt, bubble bath, foam bath, Cosmetics for packs.

Test results showing the effect of nano-sized sphingomyelin Test results showing the effect of nano-sized sphingomyelin

Claims (5)

  Cosmetics containing nano-sized sphingomyelin.   Cosmetics containing liposomes composed of phospholipids, most or all of which are sphingomyelin.   The cosmetic according to claim 2, wherein 98% or more of the phospholipid is sphingomyelin.   An external preparation containing liposomes composed of phospholipids, most or all of which are sphingomyelin.   The external preparation according to claim 4, wherein 98% or more of the phospholipid is sphingomyelin.