JP2012082226A - Oral agent for treatment or prevention of cutaneous disease - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new composition for the prevention or treatment of cutaneous diseases such as atopic dermatitis.SOLUTION: The invention provides a composition containing dihomo-γ-linolenic acid (DGLA), having preventing or treating effect on cutaneous diseases and usable as medicines, etc.

Description

  The present invention relates to a food component having a preventive or therapeutic effect on various skin diseases such as allergic dermatitis such as atopic dermatitis and contact dermatitis, eczema, and skin disorders caused by UV, or a food composition containing the same About. More specifically, it relates to providing an optimal dose for maximizing the effect of the component.

  When classifying a wide variety of fatty acids from a structural point of view, many of them have a long-chain fatty chain consisting of about 20 carbons in the molecule and two or more unsaturated moieties (double bonds). Called polyunsaturated fatty acids (PUFA). Or it is often expressed as an essential fatty acid (EFA) for some fatty acids because it is extremely important for maintaining human health from a nutritional point of view. The definition of EFA refers to linoleic acid (LA) and α-linolenic acid (ALA), which cannot be synthesized in humans in the narrow sense and must be ingested by the diet. In the broad sense, their metabolites arachidonic acid (AA ), Eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Among these, a series of fatty acids produced with ALA as the parent fatty acid is called n3 PUFA, and EPA and DHA are included in this series.

  On the other hand, as shown in FIG. 1, a similar one having LA as a parent fatty acid is called n6-type PUFA. Specifically, γ-linolenic acid (GLA) is subsequently produced from LA by Δ6 desaturase, followed by carbon chain elongation. It is metabolized to DGLA by oxidase and to AA by Δ5 desaturase.

  The physiological roles of these n6-based PUFAs have been studied in detail. Among them, GLA is associated with skin disorders (Cosmetic & Toiletries, Nissen HP, 1995, 110, P.71), diabetes and its complications ( Diabetic Medisine, Jamal GA, 1990, 7, p. 319-), rheumatoid arthritis (Arthritis Rheumatisum, Zurier RB, 1996, 39, p. 1808-) and the like. Regarding the molecular mechanism in the physiological function of GLA, as shown in FIG. 1, the active molecule is DGLA, which is a carbon chain elongation metabolite of GLA, or 1-series prostaglandin (PG1), which is a cyclooxygenase metabolite of DGLA. Or 15-hydroxyeicosatrienoic acid (15-HETrE), which is a lipoxygenase metabolite of DGLA.

  On the other hand, the physiological activity of DGLA has been partially confirmed in vivo or in vitro, and in vivo platelet aggregation inhibition (British Medical Journal, Kernoff PBA, 1977, 2, p.1441), Delayed footpad edema (Lipids, Taki H, 1993, 28, p.873 ~), blood pressure elevation suppression (Lipids, Cedric H, 1984, 19, p.699 ~), etc. -2, 10, Inhibition of cytokine production such as tumor necrosis factor (TNF-α) (Immunology, Maaike MBWD, 2003, 110, p.348 ~; The Journal of Immunology, Deniela S, 1989, 143, p.1303 ~ ), Leukotriene production inhibitory action (Archives of Dermatological Research, Iversen L, 1992, 284, p. 222-), T cell proliferation inhibitory action (Prostaglandine Leukotrienes and Essential Fatty Acids, Zurier RB, 1999, 60, p. 371-) Etc. have been reported.

  The relationship between the physiological function of organisms (especially skin) and PUFA has been studied in many fields. For example, when animals such as rats are kept for a long time in an EFA-deficient state, skin desquamation, water content reduction, water loss It has been found to be accompanied by abnormalities in skin function, such as increased amounts. In addition, it is speculated that PUFA is also heavily involved in various skin diseases such as eczema, contact dermatitis, and skin damage caused by UV. Furthermore, GLA is useful for the prevention and treatment of various diseases as described above, and it has been found that GLA is effective in skin diseases, particularly atopic dermatitis (American Journal of Clinical Nutrition). Harrobin DF, 2000, 71, p367 ~).

First of all, it became clear that the amount of LA in the serum of patients suffering from atopic dermatitis increased compared to that of healthy individuals, and at that time the amounts of metabolites from LA, DGLA and AA, decreased conversely. Turned out to be. This strongly suggests that the function of the Δ6 desaturase, which is an enzyme converting LA to GLA, in the n6 PUFA metabolic pathway may be reduced in patients with atopic dermatitis.
Therefore, it is speculated that ingestion of PUFA downstream of the Δ6 unsaturated enzyme may improve such diseases accompanied by abnormal PUPA metabolism. Among them, there are relatively many in the natural world, and in the seeds of evening primrose, blackcurrant and borage It was investigated whether ingestion of a large amount of GLA could improve various symptoms of atopic dermatitis.

  As a result, it was reported that oral intake of GLA (about 180-1440 mg / person / day) in human studies can improve skin irritation or pruritus in atopic dermatitis, especially 720 or per day. It was more effective in patients who took a high dose of 1440 mg / person. At that time, it was confirmed that GLA can increase DGLA and AA levels in the body, especially DGLA levels more effectively, and that there is a positive correlation between symptom improvement and DGLA (Prostaglandins Leukotrienes and Medicine, Mauku MS, 1982, 9, p.615-; The Lancet, Wright S, 1982, 20, p.1120-).

  Its effectiveness has been confirmed in NC / Nga mice, a model animal for atopic dermatitis, and oral intake of GLA (about 1250 mg / kg per day) has the effect of suppressing atopic dermatitis formation and IgE production. It has also been found (The 50th Annual Meeting of the Japanese Society of Allergy, Mizusada, 2000, p.999-). As described above, for the improvement of atopic dermatitis, it is speculated that the intake of GLA is useful in n6PUFA, and the intake of DGLA, which is expected to be the active body, is more effective.

  However, there is a possibility that an appropriate dose is not set in GLA intake for the purpose of correcting PUFA metabolic abnormalities such as the above-mentioned atopic dermatitis. In guinea pigs, when a large excess of GLA was administered at about 3200 mg / kg per day, the amount of DGLA in the epidermis would rather decrease compared to when GLA was ingested at about 400 mg / kg per day, and in vivo PUFA A phenomenon occurred in which the increase in the amount was not correlated (Prostaglandins Leukotrienes and Essential Fatty Acids, Navarette R, 1992, 46, p. 139). This suggests that conversion of GLA to DGLA may be inhibited when a large amount of GLA is ingested.

  That is, if a large amount of GLA is ingested, the amount of DGLA in the living body may decrease rather than increase, and there is a risk of exacerbating atopic dermatitis. Furthermore, it is known that there are individual differences in the metabolism of GLA in humans. When GLA is administered to patients with human atopic dermatitis, the degree of increased erythrocyte membrane DGLA varies from patient to patient, and among those patients with increased DGLA, skin inflammation is significantly ameliorated. In the group of patients whose DGLA level did not increase, improvement of skin inflammation was not observed (British Journal of Dermatology, Henz BM, 1999, 140, p. 685-). This also means that GLA intake is not always effective to increase the amount of DGLA, and that the optimal dose of GLA is not necessarily the optimal dose of DGLA in the treatment of atopic dermatitis. is doing.

  On the other hand, ingestion of DGLA has confirmed that the amount of DGLA in the body increases in a dose-dependent manner (58th Annual Meeting of the Japanese Society of Nutrition and Food Science, Chiga Horikawa, 2004, p.219-). It is unlikely that the amount of living DGLA will decrease even when ingested. Furthermore, the inhibition of metabolic enzymes by GLA was originally recognized as having relatively high enzyme activity, and the carbon chain elongation enzyme, which was thought to have no decrease in activity associated with aging, is also an enzyme reaction. The above shows the possibility of being affected by the substrate environment and other factors.

  As a result, the increase in DGLA when GLA is ingested may vary depending on various conditions, strongly suggesting that it is difficult to properly control the treatment of atopic dermatitis by ingesting GLA. . From the viewpoint of safety and efficacy, it is preferable to take DGLA itself more directly than GLA in the treatment or prevention of atopic dermatitis, and to supply the most suitable dose there. I think it is very important.

  However, some meats, eggs, and seafood contain dihomo-γ-linolenic acid (DGLA), but the types are limited and natural for those who do not eat meat very much, such as vegetarians. Ingestion of dihomo-γ-linolenic acid (DGLA) from food is extremely difficult. In addition, although DGLA exists in nature, its amount is extremely low and it was difficult to prepare a large amount. Therefore, as in the previous GLA test, the efficacy verification for atopic dermatitis using DGLA was actually conducted. Was in a very difficult situation. In other words, no direct proof that DGLA itself has improved atopic dermatitis has been made to the best of our knowledge, and as mentioned earlier, DGLA has been used in in vivo studies of animals or in vitro of animal and human-derived cell lines. Although it has been shown that the test has various physiological effects, it is difficult to say that it is a test that mimics atopic dermatitis, and whether DGLA can actually improve atopic dermatitis. There is no clear answer to.

  The inventors have so far obtained a microorganism deficient in Δ5 desaturase and invented a method for fermentative production of DGLA oils and fats by this strain, as shown in Japanese Patent No. 3345811, so that about 40% of the constituent fatty acids are obtained. It made it possible to prepare a large amount of triglyceride SUNTGD consisting of DGLA, and overcame the difficulties in obtaining DGLA raw materials.

Patent No.3354581

Cosmetic & Toiletries, Nissen HP, 1995, 110, P.71〜 Diabetic Medisine, Jamal GA, 1990, 7, p.319〜 Arthritis Rheumatisum, Zurier RB, 1996, 39, p.1808〜 British Medical Journal, Kernoff PBA, 1977, 2, p. 1441- Lipids, Taki H, 1993, 28, p.873〜 Lipids, Cedric H, 1984, 19, p.699〜 Immunology, Maaike MBWD, 2003, 110, p.348〜 The Journal of Immunology, Deniela S, 1989, 143, p.1303〜 Archives of Dermatological Research, Iversen L, 1992, 284, p.222〜

Prostaglandine Leukotrienes and Essential Fatty Acid, Zurier RB, 1999, 60, p.371〜 American Journal of Clinical Nutrition, Harrobin DF, 2000, 71, p367〜 Prostaglandins Leukotrienes and Medicine, Mauku MS, 1982, 9, p.615〜 The Lancet, Wright S, 1982, 20, p.1120〜 Abstracts of the 50th Annual Meeting of the Japanese Society of Allergy, Mizusada, 2000, p.999- Prostaglandins Leukotrienes Essential Fatty Acids, Navarette R, 1992, 46, p.139〜 British Journal of Dermatology, Henz BM, 1999, 140, p.685 ~ 58th Annual Meeting of the Japanese Society of Nutrition and Food Science, Chiga Horikawa, 2004, p.219〜 New development of functional lipids, Osamu Suzuki, 2001 γ-Linolenic Acid, Recent Advances in Biotechnology and Clinical Applications, Hundy YS, 2001

  An object of the present invention is to provide an appropriate amount of DGLA for safe and more effective prevention and treatment of atopic dermatitis.

  In the present invention, PUFA and its related metabolites cause quantitative and qualitative abnormalities due to various factors, and as a result of undesirable biological changes caused by them, and vice versa. Basically, PUFA and related metabolites often cause quantitative and qualitative abnormalities, and in this situation, PUFA is actively taken and the abnormalities are corrected. In principle, especially in the improvement of PUFA abnormalities such as atopic dermatitis, we found that DGLA, which is an n6-based PUFA, is extremely useful among PUFAs, and found that a lower dose than GLA is sufficient, and completed the present invention. .

Accordingly, the present invention provides a composition comprising dihomo-γ-linolenic acid (DGLA) and having a preventive or therapeutic effect on skin diseases.
This composition is, for example, a food composition or a pharmaceutical composition.
The dermatitis is, for example, allergic dermatitis, such as atopic dermatitis.
The content of DGLA in the composition is, for example, an amount suitable for ingesting 5 mg to 600 mg of dihomo-γ-linolenic acid (DGLA) per day per adult. For example, the intake of DGLA is 5 mg to 200 mg per adult per day, or 5 mg to 150 mg.

DGLA exists, for example, in the form of glycerides, phospholipids, glycolipids, alkyl esters, or free fatty acids. The glyceride is, for example, triglyceride, diglyceride, or monoglyceride. Preferably, the glyceride is triglyceride and / or diglyceride.
The composition is, for example, in the form of a pill, tablet or capsule.

  The composition of the present invention can also take the form of a food or drink that comprises dihomo-γ-linolenic acid (DGLA) and displays that it has a preventive or therapeutic effect on skin diseases. For example, a food or drink containing dihomo-γ-linolenic acid (DGLA) in an amount of 5 mg to 600 mg per adult per day, with a label indicating that it has a preventive or therapeutic effect on skin diseases It can be a thing. In addition, food and beverages containing dihomo-γ-linolenic acid (DGLA) in an amount of 5 mg to 200 mg per day per adult, with a label indicating that it has a preventive or therapeutic effect on skin diseases Or dihomo-γ-linolenic acid (DGLA) in an amount of 5 mg to 150 mg per day for an adult, a label indicating that it has a preventive or therapeutic effect on skin diseases Can be food and drink.

  DGLA is more useful as a food for preventing atopic dermatitis because the effect of preventing DGLA by atopic dermatitis can be prevented at a lower dose compared to GLA. In addition, taking the most appropriate dose is very important in terms of effectiveness.

FIG. 1 is a diagram showing the metabolic pathway of 6n polyunsaturated fatty acids (PUFA).

The present invention is described in detail below.
Food compositions include dietary supplements, and (pharmaceutical) formulations and preparations such as tablets, pills and capsules. In addition, solid or liquid foodstuffs such as dairy products (margarine, butter, milk, yogurt), bread, cakes; drinks such as beverages (tea, coffee, cocoa, chocolate drinks), fruit juices, soft drinks (eg carbonated drinks) ); Confectionery; oily food (snack, salad dressing, mayonnaise), soup, sauce, carbohydrate rich food (rice, noodles, pasta), fish food, baby food (eg infant formula, liquid or powder), Examples include pet food and food that can be cooked or cooked in a microwave.

  DGLA can be derived from any suitable source. However, there are almost no natural fat sources known to have a high DGLA content, and it is possible to extract from a beef liver, pig kidney, egg yolk, etc., in a very small amount. In recent years, microbial fermentation technology has advanced and may be derived from microorganisms such as fungi, bacteria or yeast.

  Suitable fungi are those belonging to the order of the Mucorales, for example Mortierella, Pythium or Entomophyhora. A preferred source of DGLA is from Mortierella. More preferably, it is derived from Mortierella alpina. As shown in Japanese Patent No. 334581, the inventors can prepare triglycerides in which about 40% of the constituent fatty acids are composed of DGLA by microbial fermentation using Mortierella.

In addition to DGLA, one or more additional PUFAs may be supplied. In addition to DGLA, this may be another n6 PUFA (eg, LA, GLA, AA, etc.), or an n3 PUFA (eg, EPA, DHA).
Physiologically acceptable functional derivatives of this acid that can be converted to DGLA for use in the present invention include triglycerides, diglycerides, monoglycerides containing DGLA, or as phospholipids, glycolipids, and free fatty acids and fatty acid esters. (Eg methyl or ethyl ester), may be in the form of a sterol ester.

  Preferably the PUFA is present in the oil. This can be a pure oil, a processed oil (eg a chemically and / or enzymatically treated oil) or a concentrated oil. These oils may contain 10-100% PUFA, but the content of the desired PUFA, such as DGLA, is 5% or more, preferably 10% or more, more preferably 25% in the oil if the oil is derived from microorganisms. That is all you need. The oil may contain one or more PUFAs within these percentage concentration ranges. The oil may be a single oil derived from a single cell or microorganism, or it may be a blended or mixed oil of two or more oils derived from other sources. This oil contains, for example, one or more additives such as antioxidants (eg tocopherol, vitamin E, tocotrienol, ascorbic acid derivatives, palmitate or ester, astaxanthin), sesamin, CoQ10, etc. May be.

The present invention improves the PUFA level of an individual who has eaten sufficiently with normal health, that is, an individual having a normal PUFA level, and is used for the purpose of disease prevention, health maintenance and maintenance. It is done.
However, it can also be used for individuals with low or insufficient PUFA levels. For example, it can be used for the prevention, prevention, amelioration, or treatment of diseases or conditions associated with abnormal or low levels of n3 or n6 PUFA in the blood. Therefore, the present invention provides use for subjects with low DGLA levels, such as subjects who cannot convert LA to GLA and DGLA, cannot convert GLA to DGLA, and / or cannot convert effectively. Therefore, a suitable patient need only have dysfunctional, insufficient or deficient Δ6 desaturase and / or carbon chain extender enzymes.

In particular, the present invention refers to a state in which the immune level is lowered or increased more than usual when the immune level is abnormal, such as in people with low DGLA levels, for example, atopic dermatitis. Provide use for certain subjects.
Low DGLA level or DGLA level fluctuation from normal, correction of other conditions such as contact dermatitis, eczema, various skin diseases such as UV-induced skin disorders, rheumatoid arthritis, diabetics, alcoholism Can also be used by smokers and smokers.

Next, the present invention will be described more specifically with reference to examples.
Example 1.
As mentioned above, DGLA intake was expected to be useful for the prevention and treatment of atopic dermatitis. We examined its usefulness in experimental animals. In this study, NC / Nga mice were used as model animals for atopic dermatitis. This model animal is currently recognized as one of the most useful atopic dermatitis models, and steroid external preparations and immunosuppressive external preparations that are actually used in clinical settings for atopic treatment are also effective in this model animal. Since it has been proved that it is shown, it is also widely used for screening for therapeutic drugs for atopic dermatitis.

  This animal developed dermatitis spontaneously around 8 weeks after birth in a conventional rearing environment, and its inflammation became worse and chronic over time. It is known to exhibit atopic-like skin inflammation. In addition, elevated serum IgE associated with the onset of dermatitis and marked infiltration of immunocompetent cells such as mast cells, eosinophils, and T cells in the lesion are also characteristic of this disease state.

  In this study, male / female NC / Nga mice were prepared, and three groups were established with 7 mice per group in a conventional rearing environment. The following three types of food shown in Table 1 were prepared and continued to be fed from the 5th week after weaning until the 12th week when the test was terminated by free consumption. The group is a control diet group, a high DGLA diet group, a low DGLA diet group, and SUNTGD is added to the back 2 groups. In the high DGLA group, about 1.0% of the diet is DGLA (calculated as free fatty acid amount) In the low DGLA group, about 0.5% of the diet was set to be DGLA (calculated as the amount of free fatty acid). Since the average body weight of the mice was 20 g and the average daily food intake was about 2 g, the DGLA intake in this experiment was calculated to be about 1000 mg / kg per day for the high DGLA group and for the low DGLA group. It was estimated that it was about 500 mg / kg per day. In each group, the total amount of fatty acids in the diet was uniformly 5%. Evaluation items were macroscopic score of skin inflammation under the blind, curettage behavior, and blood IgE.

  As a result of the examination, the DGLA intake group compared to the control diet group without showing any abnormalities related to body weight changes and general findings, and the gross score of skin inflammation (Table 2), curettage behavior (Table 3), plasma The production amount of IgE (Table 4) showed a statistically significant inhibitory effect in any of the evaluation items, suggesting that DGLA intake may be useful for the prevention of atopy. In addition, the fatty acid composition in the plasma (Table 5) at this time reflects the influence of the diet, and in any organ, an increase in the DGLA amount and a decrease in the LA amount depending on the dose of the DGLA feed were observed. The fatty acid composition variation in the spleen is remarkable, which is expected to have a strong influence on the physiological function of the immune system by DGLA. Furthermore, surprisingly, this preventive effect was independent of the dose of DGLA, that is, the low DGLA diet tended to have a stronger atopic preventive effect than the high DGLA diet group.

  As described above, since the dose-dependent increase in the fatty acid composition of the living body was observed in DGLA, it is clear that the action is not diminished due to absorption inhibition of DGLA itself. The above indicates that there is a strong possibility that the optimal dose of DGLA in atopy prevention effects in this model or in humans, in other words, a dose lower than the low DGLA diet used this time, will have the highest inhibitory effect. Suggest. Furthermore, focusing on the changes in plasma DGLA levels due to the DGLA diet, DGLA in plasma phospholipids was 4.3% for the low DGLA diet, which was particularly effective in improving atopic dermatitis-like symptoms, and the control diet It can be seen that the ratio of the group is 1.0%, which is about 4 times as much as the abundance ratio or about 3% increase in weight%. Such an increase in plasma DGLA level greatly contributes to the therapeutic effect of atopic dermatitis. It became clear that it was one of the parameters.

  It is considered that atopic dermatitis can be improved if humans can promote the correction of DGLA level by ingesting DGLA. In addition, as described above, GLA has also been reported for this model animal (Abstracts of the 50th Annual Meeting of the Japanese Society of Allergy, Mizusada, 2000, p.999-), and the dose at that time is about 1250 mg / day. The low DGLA diet used this time was about 500 mg / kg per day, less than half of that, and it was judged that DGLA can prevent atopy more efficiently than GLA. The In another report, ALA, an n3 PUFA, has been studied in the same model (Prostaglandins Leukotrienes and Essential Fatty Acids, Suzuki R, 2002, 66, p.43), and the exact dosage is known. However, although ALA in the living erythrocyte membrane is significantly increased by a diet containing at least ALA, no atopy prevention effects such as skin inflammation and correction of blood IgE have been observed.

Example 2.
In order to clarify the relationship between DGLA oral intake in humans and DGLA levels in the body, DGLA oral intake was examined by dietary survey, and after blood sampling, the amount of DGLA in serum phospholipids was measured. The subjects were eleven healthy men aged 60-70 years, who had a diary with meals and ingredients for a week. From the diary, the intake of each food material for meat, eggs, and fish and shellfish that are known to contain DGLA is determined. From the “Fourth Japan Food Standard Ingredients Table, Japanese Food Fat-soluble Ingredients Table (1990)” Using the DGLA content by food material that can be calculated, the daily DGLA intake of each person was calculated. From the DGLA intake for one week, the daily average DGLA intake was calculated for each person.

  On the other hand, blood was collected on the day after the last day in which a diary was recorded, and the fatty acid composition of the obtained serum phospholipid fraction was analyzed according to a conventional method. That is, lipid components are extracted from serum by the conventional Folch method, and the lipids are fractionated by thin layer chromatography (developing solution is hexane / diethyl ether / = 7/3) to obtain a phospholipid fraction. It was. The silica gel layer was scraped directly, reacted in methanol at 50 ° C. for 3 hours, and extracted with hexane to obtain a fatty acid methyl ester mixture. Pentadecanoic acid was used as an internal standard. By analyzing the fatty acid methyl ester mixture by capillary gas chromatography, DGLA (% by weight) in the total fatty acid of serum phospholipid was determined.

  As a result of the examination, it was found that there was a positive correlation between daily average DGLA oral intake and DGLA (% by weight) in serum phospholipids. When X = daily average DGLA oral intake (mg), Y = DGLA (% by weight) in serum phospholipids, the linear relationship is Y = 0.0312X + 1.361, and if DGLA intake increases by about 32 mg, serum It can be seen that DGLA in phospholipids has a relationship of 1% by weight. Further, the results of this study further indicate that human DGLA changes are more likely to occur after oral DGLA intake than mice. In the results of the previous mouse, taking the low DGLA diet group as an example, it has already been described that the amount of DGLA in plasma phospholipid increases by 3% by weight when 500 mg / kg DGLA in terms of body weight is ingested for substantially 8 weeks.

  In human studies, when converted to body weight of 60 kg, the amount of DGLA in serum phospholipids increases by 1% by weight when DGLA intake is 32 mg / 60 kg = 0.53 mg / kg. In addition, when DGLA in plasma phospholipids increased by about 3% by weight in mice, atopic dermatitis-like symptoms were more effectively improved, but conversely, the amount of DGLA in serum phospholipids increased by about 3% by weight in humans. The required amount of DGLA is calculated to be about 100 mg per day. Considering that the oral intake of GLA that can improve human atopic dermatitis is about 180-1440 mg per day, it is strongly suggested that DGLA can improve atopy with a smaller amount.

Example 3.
It is known that the skin is damaged by sunlight in skin diseases. In particular, ultraviolet rays classified as UV-B having a wavelength of 290 to 320 nm are said to be one of the largest causes of acute inflammation of the skin (sunburn), pigmentation / suntan, and skin cancer. In this study, we investigated the effects of DGLA on acute skin inflammation using a guinea pig UV-B-induced acute inflammation model to explore further possibilities for DGLA skin function. This model is one of the highly versatile animal models used for drug efficacy screening in drug development with anti-inflammatory effects.

  In this study, male Hartley guinea pigs were prepared and divided into a control diet group and a DGLA diet group. Each food was fed freely for a total of 3 weeks from the age of the animal to 5 weeks of age to 7 weeks of age when the experiment was completed. The DGLA diet used this time was prepared so that about 0.08% of the diet was DGLA (calculated as free fatty acid), unlike the composition of the mouse feed described above. In other words, since the average guinea pig body weight was about 400 g and the average daily food intake was about 30 g, the DGLA intake in this experiment was estimated to be about 60 mg / kg per day. After a free intake period of 3 weeks, the guinea pig's back hair was shaved and shaved, and the animal was held in the prone position, followed by a UV irradiator (Dermaray ™, M-DMR-I, Eisai) and UV- Using a B tube (FL-20S-E-30 lamp, center wavelength 305 nm, Toshiba), irradiation was performed at a distance of 5 cm from the tube for 15 minutes to induce an acute inflammatory reaction. The erythema reaction after induction was scored according to the Draize method under the blind.

  As a result, as shown in Table 6, the DGLA diet group showed a tendency to suppress the acute skin inflammatory reaction caused by UV-B, and in particular, a statistically significant inhibitory effect at 1 hour after UV-B exposure. Indicated. At this time, although the results are not shown, it was also confirmed that the DGLA diet group significantly increased the amount of DGLA in phospholipids of plasma, skin and other various organs as compared to the control diet group. From the above, it was revealed that the DGLA diet is useful for preventing skin damage caused by UV.

Claims (7)

  A therapeutic or prophylactic agent for atopic dermatitis comprising dihomo-γ-linolenic acid (DGLA) as an active ingredient, and the intake of DGLA is 5 mg to 600 mg per adult per day.   The therapeutic or prophylactic agent according to claim 1, wherein the intake amount of DGLA is 5 mg to 200 mg per adult per day.   The therapeutic or prophylactic agent according to claim 1, wherein the intake of DGLA is 5 mg to 150 mg per adult per day.   The therapeutic or prophylactic agent according to any one of claims 1 to 3, wherein the DGLA is present in the form of glyceride, phospholipid, glycolipid, alkyl ester, or free fatty acid.   The therapeutic or prophylactic agent according to claim 4, wherein the glyceride is triglyceride, diglyceride, or monoglyceride.   The therapeutic or prophylactic agent according to any one of claims 1 to 5, for treating a skin disease of a person having a low DGLA level.   The therapeutic or prophylactic agent according to claim 6, wherein the person having a low DGLA level is a person whose Δ6 unsaturated enzyme and / or carbon chain extending enzyme is dysfunctional, insufficient or deficient.

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