JPH0768103B2 - External skin preparation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a skin external preparation, particularly a cosmetic, which has an excellent water-retaining function of keeping moisture on the skin surface and constantly moisturizing the skin. More specifically, the present invention incorporates a lipid mixture having a water-retaining function obtained from animal cells of mammals such as cows and horses and birds such as chicken and quail into an external base containing water as an active ingredient. By means of this, external preparations for skin that exert a useful effect on diseases that are aggravated mainly due to dryness of the skin such as cracks and cracks, prevention of aging of the skin, moisturizing, smoothness, and the like, and beautiful appearance of the skin, etc. It is intended to provide cosmetics that give

Conventionally, cracks, cracks and the like generally reduce the barrier function due to the decrease of skin secretions, especially lipids, when the air is dried in the winter, and the transepidermal water loss (hereinafter referred to as TWL Is a symptom induced as a result of drawing out water in the epidermis (especially in the stratum corneum) due to an increase in size or due to a physical cause (such as washing). On the other hand, one type of keratoses called ichthyosis is a condition in which the skin is rough and dry, the surface is cracked, and it looks like scales, which is said to be particularly aggravated during the dry season in winter. In addition, a state in which the water content of the stratum corneum is about 10% even under normal conditions is called dry skin, and senile xerosis is a suitable example. As described above, the water in the stratum corneum of the epidermis normally binds to the constituent components of the stratum corneum to maintain normal skin function, but due to environmental changes (low temperature and low humidity) and aging, moisture in the stratum corneum is increased. When the content is reduced, it is closely related to the occurrence of rough skin, which causes the skin to become dry or brittle and crack. In order to deal with these symptoms, it is necessary to prevent a decrease in the water content of the stratum corneum and maintain the skin function normally, and various methods have been studied.

Conventionally, as such a method, there are a method of suppressing TWL by using an occluding agent and a method of enhancing a skin hydration effect by using a moisturizing agent.

As an example of the former, vaseline ointment is well known, and as seen in JP-A No. 54-86630, there was a method of blending a sebum-like composition to cover the skin surface to prevent drying. In these cases, in order to enhance the effect, it is necessary to increase the amount used (application amount), which causes an unpleasant feeling such as oiliness and stickiness during use, and conversely if the amount used is small. It had the drawback of weak obstruction and lack of persistence.

On the other hand, examples of the latter include ethylene glycol, propylene glycol, 1,3-butylene glycol, polyhydric alcohols such as glycerin, and moisturizers such as PCA-soda, but these have good compatibility with water. Each of them does not have very high water retention capacity, and instead of retaining water in the skin under low humidity, the moisturizer wicks water from the skin (especially noticeable with glycerin), and in high humidity, absorbs moisture in the outside air. There was a fatal defect that it gave a greasy discomfort, and conversely when the amount used was suppressed, its effect was weak and not long-lasting.

Therefore, the present inventors have solved the problems in the above-mentioned conventional methods, and conducted diligent research to find out a substance and a dosage form having a high water-retaining function, and found that a lipid mixture obtained from animal cells of mammals or birds was used. When compounded in a base for external use or a base for cosmetics, a liquid crystal state containing water is formed on the skin, and it is determined that an excellent occlusive property and water retention can be obtained, and the present invention is completed. I arrived.

That is, the present invention uses mammalian (excluding brain tissue) or avian animal cells in an organic solvent of low polarity (excluding lower alkyl alcohol) that is immiscible with water at an arbitrary ratio, or A lipid mixture containing phospholipids, glycolipids, and cholesterol as a main component, which is obtained by extraction with a mixture of the organic solvent and a lower alkyl alcohol, is added to an external base containing water as an active ingredient. The present invention relates to a skin external preparation.

Lipid mixtures applied to the present invention include mammals such as humans,
Animal cells such as cows, horses, monkeys, dogs and birds such as chickens, quails, ducks, ducks, sparrows and turkeys, especially those obtained from their cytoplasm or cell membrane.

Generally, animal tissues are broadly divided into epithelial tissues, connective and supporting tissues, muscle tissues, nerve tissues, etc., all of which consist of cells and intercellular substances surrounding them, and cells are composed of cell membrane, cytoplasm and cytoplasm. It is composed of cell nuclei. So far, many studies have been conducted on tissues or cells and intercellular substances, and their functions in living organisms and their properties have been elucidated. Also in the fields of external preparations and cosmetics, it has been common practice to incorporate extracts derived from various tissues in order to utilize the physiological activity of these tissues. Placenta extract,
Collagen (including proteolytic products), keratin, proteoglycan, elastin, hyaluronic acid, etc. can be said to be typical utilization substances in this field. Most of these substances are mainly present in intercellular substances or connective tissues in a narrow sense or in extra-tissue substances such as melons, and belong to proteins and amino acids, mucopolysaccharides, monosaccharides and salts. Therefore, when extracting these substances, after homogenizing the tissue, it is usually necessary to perform acid or alkali treatment or enzyme treatment, and then perform water or solvent extraction such as water / alcohol system. Met.

On the other hand, with regard to cells and their intracellular substances (mainly lipids, sugars, etc.) in tissues, almost no research has been done on external agents, especially cosmetic functions and uses. Even when extracting
The reality is that the cell portion is discarded as an unnecessary residue portion. Based on such a situation, the present inventors have studied the applicability as a skin external preparation by paying attention to the cell portion, and finally succeeded in extracting a material having a skin water-retaining function from the cells. This is a formulation.

Therefore, even when extracting the lipid mixture according to the present invention from the above-mentioned mammalian or avian animal cells, a method relying only on the polarity and extraction power of the solvent described below, for example, mixing an organic solvent with a tissue, an organ, etc., and applying a grinder Of course, the extraction method is also good, but in order to further improve the extraction efficiency and obtain a lipid mixture with less contaminants, an operation, that is, pretreatment, that can improve the occupancy rate of cells in the tissue and can be purified is performed. Is advantageous. As such pretreatment, (1) a tissue / organ such as an organ or skin is subjected to a high speed centrifuge to dehydrate and remove water-soluble components in the tissue,
Concentrate.

(2) The tissue is homogenized with an organic solvent miscible with water at an arbitrary ratio, for example, methanol, ethanol, acetone, THF or the like, and concentrated for dehydration.

(3) Mince the tissue, dissociate the cells by acting a protease (eg, triprine), etc., and then centrifuge,
The supernatant is removed and the cells are concentrated. And the like. After that, it is preferable to sufficiently extract with an organic solvent.

The organic solvent used here is preferably a solvent that can efficiently extract lipid components in animal cells, and has a low polarity, in other words, an organic solvent that is immiscible with water at an arbitrary ratio, such as n-hexane. , N-heptane, petroleum ether, ethyl ether, chloroform and the like alone or in a mixed solvent, and further a mixture of the above organic solvent and a lower alkyl alcohol, specifically n-hexane / ethanol.
A mixed solvent such as ethyl ether / ethanol or chloroform / methanol is used. And further the extract is
After washing with water or an aqueous salt solution such as Kcl or Cacl ₂ , the solvent is distilled off to obtain the target lipid mixture.

The lipid mixture thus obtained is generally a pale yellow or yellow waxy or solid substance, and from a compositional point of view of thin layer chromatography (omitted), phosphorus mixtures such as sphingomyelin are observed. Lipids, glycolipids such as cerebroside, and cholesterol are present as major constituents, and they are a complex mixture containing trace amounts of polysaccharides, proteins, salts and the like.

Hereinafter, a production example will be described in order to further describe in detail a method for extracting a lipid mixture from animal cells existing in a tissue or an organ.

Production Example 1. 100 g of fresh beef liver was homogenized with 15 g of 95% ethanol, 250 ml of 95% ethanol was added, and the mixture was stirred. This was filtered to separate the extract from the residue, 300 ml of n-hexane was added to the residue, and the mixture was stirred with sufficient extraction. The extract obtained by filtering this is a 0.75% Kcl aqueous solution 6
It was washed with 0 ml of water. After repeating this operation twice, the organic solvent was distilled off at 40 ° C. or lower under reduced pressure to obtain 7.5 g of a pale yellow solid lipid mixture.

Production Example 2. 100 g of fresh chicken meat was minced, 50 ml of a 0.1% trypsin solution was added thereto, the mixture was allowed to act at 37 ° C. for 30 minutes, and then centrifuged to remove the supernatant. After that, 500 ml of chloroform-methanol (2: 1 V / V) mixed solvent was added to the precipitation part.
Was added, mixed and stirred, and extracted sufficiently. The extract obtained by filtering this was washed with 80 ml of 0.04% Cacl ₂ aqueous solution.
Then, the extract was distilled off the organic solvent under reduced pressure at 40 ° C. or lower to obtain 5.4 g of a pale yellow waxy lipid mixture.

Next, the blending amount of the lipid mixture in the present invention can be widely varied depending on the dosage form of the external skin preparation or the cosmetic to be applied, but is generally 0.05 to 90% by weight, preferably 0.05.
Is in the range of up to 20% by weight. That is, this lipid mixture has a high liquid crystal forming ability in the form of taking up water in a mixed system with water, and thus has a large water retaining ability on the skin after application, but when mixed in a large amount, it does not become oily. In addition, it may give a sticky feeling and may not be preferable as a cosmetic.

On the other hand, as raw material components other than water used in the present invention, oils and fats usually applied to external preparations for skin and cosmetics, surfactants, moisturizers containing polyhydric alcohols, various medicinal components, corrosion Most of the components such as agents are included, and they are appropriately selected and adjusted according to the purpose, application, dosage form and the like.
However, the important point here is that it is important to have a prescription system that does not inhibit liquid crystal formation after application of the product to the skin, and thus, for example, for oils and fats, myristic acid, palmitic acid, stearic acid, cetanol, Stearyl alcohol, beeswax, when liquid fats typified by liquid paraffin, liquid paraffin, squalane, soybean oil, olive oil, octyldodecyl myristate, and the like, which are typified by liquid crystal fats, are particularly preferable, and When the liquid fat and the solid fat are combined and combined, it is more effective to use the liquid fat latch. On the other hand, for polyhydric alcohols, ethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin,
Diglycerin, polyethylene glycol, polyglycerin and the like can be mentioned, but in view of liquid crystal formation, glycerin or a mixture of glycerin and other polyhydric alcohol is more preferable.

As described above, in the case of a skin external preparation or a cosmetic composition composed of a lipid mixture, oils and fats, polyhydric alcohols, water, etc., a volatile substance (especially water) is applied in the prescription system or after being applied to the skin. When the content ratio of the lipid mixture accompanying transpiration of (1) reaches the range of 0.5 to 20% by weight, preferably 1 to 5% by weight based on the total weight of the residue, a liquid crystal in which water is taken in is formed, It has the best water retention and blocking effect.

Here, the results of evaluating how the lipid mixture according to the present invention has a high liquid crystal forming ability in the state of taking in water and the water retaining ability are shown.

1 Hygroscopic Evaluation Sample: The lipid mixture according to the present invention obtained in Production Example 1 and glycerin and propylene glycol were used as comparative products.

Method: Weigh 5 g of each of the above samples into a Petri dish with a diameter of 3 cm, set this in a desiccator adjusted to a relative humidity of RH = 98%, and measure the sample weight after 24 hours and 48 hours. The moisture absorption rate ^{* 1)} was calculated. The results are shown in Table-1.

* 1) Moisture absorption rate = sample weight after aging (g) / 5 (g) x 100 2 Evaluation of water retention capacity Sample: (a) Lipid mixture according to the present invention obtained in Production Example 1 and (b) sphingomyelin (phospholipid), (c) cerebroside (glycolipid), (d) as comparative products Cholesterol, an equivalent mixture of (e) sphingomyelin and cerebroside, an equivalent mixture of (f) sphingomyelin and cholesterol, and an equivalent mixture of (to) cerebroside and cholesterol were used.

Method: Weighed 1g each of the samples (a) to (g) swollen by adding 4 times the amount of water (80% by weight water content) to a petri dish with a diameter of 3 cm. Is set in a furan oven at a temperature of 5 ° C and RH of 45%, and the water content is measured after 1 hour, 3 hours, 5 hours, and 7 hours.
The water content ^{* 2)} retention rate was calculated using the average value of three times. still,
The water content was measured using a trace moisture meter AQ-3 manufactured by Hiranuma Sangyo. The results are shown in Table-2.

* 2) As shown in the results of Table-1 and Table-2, it was demonstrated that the lipid mixture according to the present invention has moderate hygroscopicity and, on the other hand, high water retention ability and excellent water retention. Thus, even if the individual component or the mixture of two kinds contained in the lipid mixture according to the present invention does not have such a high water retention ability, the lipid mixture according to the present invention has an excellent water retention ability. Regarding the point of having the above, exactly as described above, the lipid mixture according to the present invention has a high liquid crystal forming ability in a state of incorporating water,
Therefore, it can be said that this is proof that the water retention is enhanced.

Furthermore, the results of the assay and the results of the use test carried out to evaluate the external preparation for skin of the present invention containing the lipid mixture according to the present invention are shown below.

3 Water Retention Function Evaluation Sample: An ointment (A) containing lecithin and sorbitan monostearate instead of the lipid mixture in the ointment of Example 1 described below as a comparative product, and the ointment of the present invention shown in Example 1 described below. The mixed ointment (B) and the ointment (C) containing an equal mixture of sphingomyelin and cerebroside were used.

Method: Weigh 5 g of each of the above samples into a petri dish with a diameter of 3 cm, set this in a Flanker at 35 ° C and 45% RH, and after 1 hour, 3 hours, 5 hours, and 7 hours. The weight of the sample was measured to calculate the water evaporation rate ^{* 3)} from the ointment system. The results are shown in Table-3.

* 3) Moisture evaporation rate = [5 (g) -Sample weight after aging (g)] / 0.3
9 (g) x 100 4 Evaluation of occlusivity Sample: The same inventive product and comparative products (A), (B) and (C) as those used for the water retention function evaluation were used.

Method: Put 10 g of water in a deep petri dish with a diameter of 35 mm, cover with a paper roll (Toyo Roshi Paper No. 5C), and apply a fixed amount (0.2 g) of each of the above samples evenly onto this paper roll, The residual water amount (8) after standing at 35 ° C. for 15 hours was measured, and the clogging rate ^{* 4)} was calculated. The results are shown in Table-4.

* 4) 5 Evaluation of stratum corneum water content and use test evaluation Sample: The same inventive product and comparative products (A), (B) and (C) as those used for the water retention function evaluation were used.

Method: Ask 5 female panelists to apply the above samples to the inner part of the forearm, and measure the feeling of use (sensory evaluation) and the change in water content in the stratum corneum over time by the ^{* 5)} impedance meter method. , And the average value (n = 5) was plotted (see FIG. 1). The results of sensory evaluation are shown in Table-5.
Shown in.

* 5) Impedance meter method: The amount of water in the stratum corneum is measured by measuring the thin electrical property (μ) in the stratum corneum of the skin. Measuring instrument; impedance meter model IB-355 manufactured by IBS, measuring conditions: 20 ° C, RH = 50%.

As shown in the results of Tables 3 to 5 and FIG. 1, the external preparation for skin of the present invention has a low water transpiration amount and therefore has water retention, has good occlusive property, and maintains the water content of the stratum corneum for a long time. In addition, it became clear from the point of view of use that it was excellent without stickiness.

Examples will be shown below. The mixing ratio is% by weight.

Example 1. Ointment Liquid paraffin 65 Vaseline 5 POE (20) sorbitan monostearate 6 Beeswax 3 Beef liver cell extract lipid mixture 3 Glycerin 10 Preservative 0.2 Water 7.8 Example 2. Cream stearic acid 2 Stearyl alcohol 1 Reduced lanolin 1.8 Squalane 10 Lipid cell extract lipid mixture 1.2 Octyldodecanol 6 POE (25) Cetyl ether 3 Glyceryl monostearate 2 Fragrance 0.3 Preservative 0.2 Glycerin 5 Water 67.5 Example 3. Emulsion POE addition (50) Hardened castor oil 1 Palm oil Fatty acid monoglyceride 1 Horse meat cell extract lipid mixture 0.5 Oleic acid triglyceride 7.5 Glycerin 2.5 Perfume 0.2 Preservative 0.2 Water 87.1 Soda 0.2 ethanol 1 0 Perfume 0.1 Preservative 0.1 Water 83.8

[Brief description of drawings]

FIG. 1 shows the results of conductivity (μ) in the stratum corneum of the skin after a certain time (30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes) by the impedance meter method, X
Is the product of the present invention, Y is the comparative example (A), Z is the comparative example (B), W
Is a comparative example (C).

─────────────────────────────────────────────────── ─── Continued Front Page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 35/34 7431-4C 35/407 ADA 7431-4C 38/00 (72) Inventor Shuzo Nagashima 27 Takashimadai, Kanagawa-ku, Yokohama, Kanagawa Prefecture Pola Chemical Industry Co., Ltd. Company Yokohama Institute (72) Inventor Yukio Mikami 27 Takashimadai, Kanagawa-ku, Kanagawa, Kanagawa Prefecture 1 Pola Chemical Industry Co., Ltd. Yokohama Institute (72) Inventor Masayoshi Nagai 27 Takashimadai, Kanagawa-ku, Yokohama 1, Kanagawa Kasei Kogyo Co., Ltd. Yokohama Laboratory (56) Reference JP-A-52-38011 (JP, A) JP-A-59-39338 (JP, A) JP-A-59-1404 (JP, A) JP-B-36- 2000 (JP, B1) Japanese Patent Publication No. 4-57641 (JP, B2) Chemical Abstracts Vol. 92 37 304

Claims (3)

[Claims] 1. A mammalian (excluding brain tissue) or an avian animal cell is used, which is a low-polarity organic solvent (excluding lower alkyl alcohol) that is immiscible with water at an arbitrary ratio, or A lipid mixture containing phospholipids, glycolipids, and cholesterol as a main component, which is obtained by extraction with a mixture of the organic solvent and a lower alkyl alcohol, is added to an external base containing water as an active ingredient. External preparation for skin. 2. The organic solvent is n-hexane, n-heptane,
The external preparation for skin according to claim 1, which is selected from petroleum ether, ethyl ether and chloroform. 3. The external skin preparation according to claim 1, which is a cosmetic.