JP2005179211A - External preparation composition for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation composition which is used for the skins, is inexpensive, has excellent quality stability, and has a skin symptom-improving or -curing effect. <P>SOLUTION: This external preparation composition for the skin, comprising a triglyceride, diglyceride, monoglyceride and a free fatty acid, contains one or more of γ- linolenic acid and γ-linolenoyl glyceride. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a skin external preparation composition comprising an oil or fat composition containing γ-linolenic acid (hereinafter sometimes abbreviated as GLA) having an ability to promote animal cell growth as an active ingredient.

2. Description of the Related Art Conventionally, in the field of topical skin preparations, many studies have been made to activate skin cells and activate skin functions themselves to improve skin symptoms, develop anti-inflammatory effects or wound healing effects. Conventionally, various substances such as hormone preparations, vitamin preparations, herbal extracts such as γ-oryzanol and saponin, plant lectins, mushroom extracts, and animal-derived proteins have been used as such external preparations for skin.
Among these substances, α-hydroxy acids and retinol are effective in repairing wrinkles as substances that have the effect of improving skin aging symptoms such as wrinkles, and substances that prevent skin aging and inflammation from sunlight. It is known. However, glycolic acid, lactic acid, and the like, which exhibit particularly effective action among α-hydroxy acids, are lipophilic, so that percutaneous absorption is poor, and when the amount is increased, undesirable side effects such as skin irritation are exhibited. There was also. In addition, since retinol is easily oxidized when exposed to air, it is usually used as an ester with a fatty acid. However, since this fatty acid ester is fat-soluble, it is difficult to incorporate into a water-soluble substrate. It was.
Healing wounds (surgical incisions, wounds or ulcers in the gastrointestinal tract, exfoliation, lacerations, cuts, sores, so called bed sores, sores, infections, etc.) cell proliferation and formation of epithelial tissues Depending on the drug, a drug that stimulates or promotes the differentiation and proliferation processes of cells included in the wound healing process is considered effective. In addition to extracts such as aloe as active ingredients, antibiotics, anti-inflammatory agents, kallikrein, adenine, nicotinic acid, allantoin, vitamin A, zinc, cAMP derivatives (for example, see Patent Document 1) Attempts have also been made to use the cell growth factor (b-EGF) (see, for example, Patent Document 2). However, the active ingredient may not be able to obtain a sufficient effect, is difficult to produce, has a high production cost, and the active ingredient is chemically unstable. There has been a demand for an external preparation for skin that is excellent and has an effect of improving skin symptoms or healing.

JP 63-107935 A Japanese Patent Laid-Open No. 3-106823

  This invention is made | formed in view of the said situation, and it aims at providing the skin external preparation composition which is cheap, excellent in quality stability, and has the improvement effect or healing effect of a skin symptom.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the above object can be achieved by an oil and fat composition containing a specific substance having animal cell growth promoting ability. The present invention has been completed based on such findings.
That is, the present invention provides an oil and fat composition containing triglyceride, diglyceride, monoglyceride and free fatty acid, and provides a skin external preparation composition containing at least one selected from γ-linolenic acid and γ-linolenic acid glyceride. It is.

  ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation composition which is cheap, is excellent in quality stability, and has the improvement effect or healing effect of a skin symptom can be obtained.

There is no restriction | limiting in the fatty acid which comprises the triglyceride, diglyceride, and monoglyceride which are the components of the skin external preparation composition of this invention, For example, a C2-C24 saturated fatty acid and unsaturated fatty acid are mentioned. Preferred fatty acids include caprylic acid, capric acid, myristic acid, myristoleic acid, pentadecenoic acid, palmitic acid, palmitoleic acid, stearic acid, arachidic acid, behenic acid, lignolic acid, serotic acid, oleic acid, linoleic acid, α- Linolenic acid, γ-linolenic acid, octadecatetraenoic acid, eicosenoic acid, eicosadienoic acid, eicosatrienoic acid, eicosatetraenoic acid, arachidonic acid, eicosapentaenoic acid, docosadienoic acid, docosapentaenoic acid, docosahexaenoic acid An acid etc. are mentioned.
There is no restriction | limiting in particular as a glyceride, Although it can use even a chemical synthetic thing, a thing derived from a plant and an animal, and a thing derived from microorganisms, the thing derived from a plant or microorganisms is preferable from a point with easy acquisition.
The content ratio of triglyceride, diglyceride and monoglyceride contained in the external preparation for skin of the present invention is 10 to 79% by mass, 20 to 20%, respectively, with respect to the total amount of glyceride from the viewpoint of preventing variation in animal cell proliferation effect. 70 mass% and 1-70 mass% are preferable. The content ratio of triglyceride, diglyceride, and monoglyceride is more preferably 10 to 70% by mass, 25 to 60% by mass, and 3 to 65% by mass with respect to the total amount of glyceride, respectively. Most preferably, they are 10-65 mass%, 30-60 mass%, and 5-60 mass%, respectively, with respect to the total amount of glycerides.
The glyceride having such a composition can be produced by a known method. For example, it can be produced by a method in which triglyceride type fats and oils are derived into diglycerides and monoglycerides using a chemical catalyst or an enzyme catalyst (see, for example, JP-A Nos. 2000-236888 and 2000-333688).

GLA which is an active ingredient of the external composition for skin of the present invention may exist not only as a free fatty acid but also as an ester. “GLA content” refers to free fatty acids obtained by hydrolyzing glycerides from all GLA derivatives in the skin external preparation composition of the present invention, and free existing in the skin external preparation composition. Calculated from the sum of fatty acids. For example, when GLA exists as an ester, the amount of free GLA obtained by hydrolyzing the ester may be measured.
What is necessary is just to adjust content of GLA suitably according to the dosage form and kind of skin external preparation composition. Generally, 5 mass% or more is preferable with respect to the total amount of the fatty acid which comprises a glyceride, and a free fatty acid from the point which prevents the dispersion | variation in the healing effect by a dosage form or a use use. More preferably, it is 10 mass% or more, More preferably, it is 20 mass% or more. Although there is no particular upper limit to the content of GLA, even if it exceeds 98 mass%, the healing effect is not further improved, and 98 mass% or less is preferable from an economical viewpoint.
GLA can also be obtained by chemical synthesis. Plant seeds such as borage, evening primrose, cypress, alga such as Spirulina, Cunninghamella, Mortierella, Mucor It can also obtain from microorganisms, such as. When the obtained GLA is a derivative, it may be used as it is, or may be subjected to hydrolysis treatment or transesterification treatment.

The skin external preparation composition of this invention can be manufactured by mixing a glyceride and GLA fats and oils with the said predetermined ratio by a well-known mixing method. Moreover, the skin external preparation composition of this invention extracts the microbial body fats or oils or microorganism secretion fats and oils containing GLA from the microorganisms containing GLA, and hydrolyzes or transesterifies this GLA containing fats and oils. Can be obtained.
This GLA-containing fat / oil can be obtained by culturing a microorganism having a GLA-containing fat / oil producing ability by a conventional method. As described above, various microorganisms such as filamentous fungi, yeasts, and algae can be cited as microorganisms having the ability to produce GLA-containing fats and oils. For example, microorganisms having the ability to produce γ-linolenic acid-containing oils and fats include microorganisms belonging to the genus Mortierella described in JP-A-60-168391, JP-A-63-283589, etc. Examples include microorganisms belonging to the genus Mucor and microorganisms belonging to the genus Rhizopus described in JP-A-63-133994.
More specifically, examples of microorganisms belonging to the genus Mortierella include Mortierella isabellina IFO7824 and Mortierella ramaniana var.angrispora IFO8187. Examples of microorganisms belonging to the genus Mucor include Mucor circinelloides HUT1121 (FERM P-9359) and Mucor javanicus HUT1162 (FERM P-9360).

The medium for culturing the microorganism may be any medium as long as the microorganism can grow well and produce the desired lipid, such as a carbon source, a nitrogen source, inorganic salts, and if necessary, an amino acid suitable for the growth of the microorganism. Those containing these components are used. As the carbon source, saccharides such as glucose, starch and molasses, organic acids, sodium acetate and the like can be used, and saccharides such as glucose are particularly preferable. Examples of the nitrogen source include ammonium salt, yeast extract, corn steep liquor, peptone and the like. Inorganic salts include magnesium salts, calcium salts, phosphates, iron salts, copper salts and the like.
When culturing, if a carbon source, nitrogen source or phosphate is added to the medium from the beginning, it may adversely affect the growth of microorganisms. , Γ-linolenic acid productivity can be improved, which is preferable.
Other culture conditions, such as temperature and culture time, may be set to preferable conditions in consideration of the medium composition, target γ-linolenic acid content and lipid productivity. The temperature is usually about 20 to 35 ° C, preferably 25 to 30 ° C, the pH is usually about 3 to 7, preferably 3.5 to 6.5, usually about 72 to 240 hours, preferably 96 to 168 hours. Just do it.

Since lipids containing GLA are usually accumulated in microbial cells, the culture solution is solid-liquid separated by a conventional method to obtain cells containing lipids containing GLA. Depending on the use of GLA, the cells can be used as they are, but in order to further extract and purify the fats and oils, the cells can be crushed by the methods described in the Bligh & Dyer method, the Forich method, and Japanese Patent Application Laid-Open No. 57-144986. Solvent extraction can be performed to obtain the target GLA-containing fat.
The skin external preparation composition of the present invention can be obtained by subjecting the GLA-containing oil obtained as described above to hydrolysis treatment or transesterification treatment by a known method. When the skin external preparation composition of the present invention is obtained by such a method, the content ratio of GLA in the oil / fat composition is determined by gas chromatography after taking a part of the oil / fat composition and methyl esterifying ( (See JP-A-57-144986).

The skin external preparation composition of the present invention may contain other components generally used as skin external preparation components as long as the effects of the present invention are not inhibited. Examples of other components include purified water, alcohols, oily substances, anti-dandruff agents, fungicides, medicinal ingredients, preservatives, thickeners, astringents, moisturizers, powders, perfumes, emulsion stabilizers, pH Examples thereof include regulators. When using glycerides or GLA derived from plants or microorganisms, other components derived from plants or microorganisms may be included.
Examples of alcohols include ethanol, higher alcohols having linear or branched alkyl groups or alkenyl groups, and examples of oily substances include hydrocarbons such as liquid paraffin, petrolatum, solid paraffin; liquid lanolin, lanolin Lanolin derivatives such as fatty acids; silicone derivatives such as dimethylpolysiloxane, polyether-modified polysiloxane, amino-modified polysiloxane, higher alcohols such as higher fatty acid esters, higher fatty acids, long-chain amidoamines having alkyl groups or alkenyl groups; Animal and vegetable oils such as mink oil and olive oil are listed. Examples of medicinal ingredients include vitamins. Examples of the preservative include parabens, and examples of the thickener include water-soluble polymer compounds. Examples of the humectant include propylene glycol, glycerin, carbitol, 3-methyl-1,3-butanediol, and saccharides.

The dosage form of the external preparation for skin of the present invention is not particularly limited, and may be used as it is, cream, emulsion, lotion, ointment, powder, haptic, powder, dripping, patch. In addition, a dosage form of a normal external preparation for skin such as an aerosol can be applied.
What is necessary is just to adjust the usage-amount of the skin external preparation composition of this invention suitably according to a use. For example, when blended in cosmetics, the concentration in the cosmetics can usually be about 0.001 to 100 mg / ml, preferably 0.01 to 10 mg / ml, more preferably 0.01 to 1 mg / ml. Blend as follows. In addition, when used for the treatment of wounds (including itching), the concentration in the therapeutic agent can usually be 0.001 mg / ml or more (used as it is), preferably 0.01 to 500 mg / ml, More preferably, it mix | blends so that it may become 0.01-100 mg / ml.

EXAMPLES Next, although an Example demonstrates this invention further in detail, this invention is not limited at all by these examples.
The fatty acid composition of the raw oil and fat and skin external preparation composition used in the following Examples and Comparative Examples were methyl esterified by the method described in JP-A-57-144896, and measured by gas chromatography. Moreover, the constituent glyceride composition of the skin external preparation compositions of Examples and Comparative Examples is based on the Iatroscan method (J. Jpn. Oil Chem. Soc., Vol 35, No. 8, 625-631 (1986)). It calculated | required by Iatroscan TH-10 type | mold (made by Yatron) which combined the thin layer chromatograph (TLC) and the flame ionization detector (FID). That is, 1 microliter of the sample solution was dropped on one side of a silica gel thin layer rod (Chromarod S-111, manufactured by Yatron), then the solvent was developed, and after the solvent development, the silica gel thin layer rod was removed from the analyzer TH-10. The sample was attached to a mold and analyzed under the following conditions.

Sample solution concentration: 20 mg / milliliter acetone TLC developing solvent and developing conditions Developing solvent: hexane / diethyl ether / acetic acid = 70/30/1 (volume ratio)
Deployment distance: 10.0cm
Iatroscan analysis conditions Hydrogen flow rate: 160ml / min
Air flow rate: 2.0ml / min
Scan speed: 30 sec / SCAN
Detector: Hydrogen flame ionization detector (FID)

Example 1 (Production of skin preparation for external use)
A reaction system containing 100 g of GLA-containing fats and oils having the fatty acid composition shown in Table 1 (produced by Idemitsu Kosan Co., Ltd., trade name: Granoyl HGC, GLA: 25.9% by mass) and 100 g of distilled water was added to Rhizopus niveus-producing lipase (Amano). 20,000 units of Enrase Co., Ltd., Newase F3G, 30,000 U / g) were added and reacted at 30 ° C. for 48 hours with stirring.

After adding 10 mass% sodium hydroxide aqueous solution to the obtained decomposition reaction product and adjusting the pH of the decomposition reaction product to 8-9, the oil content in the decomposition reaction product is extracted using 200 ml of diethyl ether and washed with water. After dehydration, the ether was removed to obtain 56.4 g of oil (skin external preparation composition).
Constituent glyceride composition analysis was performed by the above method using a part of the external preparation for skin, and a fatty acid composition was analyzed by gas chromatography after methyl esterifying a part of the external preparation for skin. The results are shown in Table 3. In Table 3, for example, C _{16: 0} means a fatty acid having 16 carbon atoms and no double bond, and C _{18: 3} means a fatty acid having 18 carbon atoms and 3 double bonds. To do.

Example 2 (Production of skin external preparation composition)
300 g of 3 g water, 30 g glycerin and Alcaligenes sp. Production lipase (manufactured by Meito Sangyo Co., Ltd., lipase PL, 90,000 U / g) are added to 100 g of the same GLA-containing fat and oil used in Example 1. The mixture was reacted at 30 ° C. for 72 hours with stirring.
After adding 10 mass% sodium hydroxide aqueous solution to the obtained decomposition reaction product and adjusting the pH of the decomposition reaction product to 8-9, the oil content in the decomposition reaction product is extracted using 200 ml of diethyl ether and washed with water. After dehydration, the ether was removed to obtain 87.9 g of oil (skin external preparation composition).
Constituent glyceride composition analysis was performed by the above method using a part of the external preparation for skin, and a fatty acid composition was analyzed by gas chromatography after methyl esterifying a part of the external preparation for skin. The results are shown in Table 3.

Example 3 (Production of external preparation for skin)
In Example 1, as GLA-containing fats and oils, GLA-containing fats and oils having the fatty acid composition shown in Table 2 (made by Idemitsu Kosan Co., Ltd., trade names: Granoyl CS, GLA: 7.9% by mass) were used. A skin external preparation composition was obtained by the same enzyme treatment and extraction as in Example 1.

Table 3 shows the analysis results of the obtained skin external preparation composition.
Comparative Example 1 (Production of skin preparation for external use)
In Example 1, instead of using GLA-containing fats and oils, the same treatment as in Example 1 was performed except that safflower oil not containing GLA (manufactured by SIGMA) was used to obtain a skin external preparation composition. Table 3 shows the analysis results of the obtained skin external preparation composition.

Example 4 (Healing effect test)
The healing effect of the external preparation for skin obtained in Examples 1 to 3 and Comparative Example 1 was evaluated.
10 g of glycerin, 10 g of liquid paraffin and 79 g of white petrolatum were dissolved while heating to 80 ° C., then cooled to 45 ° C., and 1 g of the external preparation for skin obtained in Example 1 was added and mixed. Was rapidly cooled to prepare a uniform ointment. This was designated as Example 1 ointment. Similarly, Example 2 ointment, Example 3 ointment and Comparative Example 1 ointment were prepared using the skin external preparation compositions obtained in Examples 2 and 3 and Comparative Example 1.
The healing effect of these ointments was evaluated by the following method. That is, 20 women aged 50 to 60 years with aging symptoms (wrinkles) on the skin are divided into 4 groups of 5 people, the ointment of Example 1 is assigned to the first group, and Example 2 is assigned to the second group. The ointment of Example 3 was used for the third group, the ointment of Comparative Example 1 was used for the fourth group for one month, and the condition of wrinkles on the skin before and after use was determined according to the following evaluation criteria. evaluated. The evaluation results are shown in Table 4. In addition, the numerical value of Table 4 shows the number of people corresponding to each evaluation standard.
<Evaluation criteria>
Effective: Remarkable disappearance of wrinkles and recovery of epidermis.
Slightly effective: Improvement effects such as shallow wrinkles and inconspicuousness are observed.
No effect: No effect is seen before and after use.

  The skin external preparation composition of the present invention has the ability to promote epithelial formation in humans and animals, and can be expected to have a healing effect in the treatment of stains, wrinkle countermeasures, wounds (including wrinkles) and the like due to epidermal metabolism.

Claims (7)

  An oil and fat composition containing a triglyceride, a diglyceride, a monoglyceride and a free fatty acid, and containing at least one selected from γ-linolenic acid and γ-linolenic acid glyceride.   The skin external preparation composition according to claim 1, wherein the content ratio of the triglyceride, diglyceride and monoglyceride is 10 to 79 mass%, 20 to 70 mass% and 1 to 70 mass%, respectively, with respect to the total amount of glyceride.   The skin external preparation composition according to claim 2, wherein the content ratio of the triglyceride, diglyceride and monoglyceride is 10 to 70 mass%, 25 to 60 mass% and 3 to 65 mass%, respectively, with respect to the total amount of glyceride.   The skin external preparation composition according to any one of claims 1 to 3, wherein a content ratio of γ-linolenic acid is 5% by mass or more based on a total amount of fatty acids and free fatty acids constituting the glyceride.   The skin external preparation composition according to any one of claims 1 to 4, which is obtained by hydrolysis treatment or transesterification treatment of a microbial oil or fat or a microbial secretion fat.   The skin external preparation composition according to claim 5, wherein the microorganism is a genus Mortierella.   The skin external preparation composition according to claim 5, wherein the microorganism is a genus Mucor.