JP3051375B2 - Antiallergic agent containing conjugated linoleic acid as active ingredient - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an antiallergic agent containing conjugated linoleic acid as an active ingredient. More specifically,
The present invention reduces leukotrienes B4 and C4 as typical chemical mediators closely related to the onset of allergy, suppresses the production of immunoglobulins related to food allergies, and suppresses the production of immunoglobulins that act antiallergicly. The present invention relates to an antiallergic agent (food, pharmaceutical) containing conjugated linoleic acid as an active ingredient and having an increasing action.

[0002]

2. Description of the Related Art Recently, the number of patients suffering from bronchial asthma, allergic diseases such as hay fever in adults and atopic dermatitis in children is increasing, and it is becoming a major social problem. Allergic symptoms are caused by immunoglobulin E caused by antigens and antibodies in the body.
(IgE antibody) is known to be produced, resulting in the stimulation of the cell membrane of mast cells and the release of histamine and leukotriene. Furthermore, since the released substance has a vascular permeability promoting action and a smooth muscle contracting action, leukocytes and proteins leak from blood vessels,
Inflammation causes the bronchi to contract and cause asthma.

That is, since IgE antibodies released from B cells by allergens are associated with the release of leukotriene in mast cells and the onset of allergy, suppressing such a chemical mediator, leukotriene, requires It has been implicated in allergic effects. Also, immunoglobulins involved in the suppression of the development of food allergies, that is, immunoglobulins M (IgM) having a basic immunity-promoting effect, and immunoglobulins A (IgG) which suppress the production of IgE associated with the development of allergies and cause inhibition of allergen absorption ( Increasing the production of each of IgA) and immunoglobulin G (IgG) that causes inhibition by competition with IgE acts antiallergic and can be expected to have an antiallergic effect.

[0004] Conventionally, antihistamines and corticosteroids have been orally administered or used as ointments as antiallergic drugs. However, drowsiness, gastrointestinal disorders, liver disorders, diabetes,
In addition to side effects such as hypertension, it is a temporary treatment, and there are problems such as symptoms appearing again when drug use is stopped.

On the other hand, conjugated linoleic acid has been isolated from fried meat (YL Ha et al., Carcinogenesis, 8, 1881-).
1887, 1987), and the following reports have been made on its various effects. Anti-carcinogen (Canc
er Research, 51, 6118-6124, 1991, Cancer Research,
54, 1957s-1959s, 1994), a method for increasing animal feed conversion efficiency (Japanese Patent Application Laid-Open No. Hei 8-505775), a method for preserving food and a preservative therefor (Japanese Patent Publication No. 6-612).
No. 46), a method for preventing weight loss, reduction in weight gain, and anorexia caused by immunostimulation (US Pat. No. 5,43)
0,066), a method of lowering body fat (US Pat. No. 5,554,646). However, to the knowledge of the present inventors, no report has been made yet that conjugated linoleic acid has an antiallergic effect.

[0006]

DISCLOSURE OF THE INVENTION The present invention is free from various side effects of the conventional antiallergic agents as described above,
An object is to provide an antiallergic agent that is extremely safe for the human body.

[0007]

Means for Solving the Problems The present inventors have conducted intensive studies on the indices effective for the treatment of allergic diseases with leukotriene which is a chemical mediator and immunoglobulin which is involved in the development of food allergy. The inventors have found that conjugated linoleic acid has an antiallergic effect in a relatively small amount, and have completed the present invention. That is, the present invention provides an antiallergic agent containing conjugated linoleic acid as an active ingredient.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The conjugated linoleic acid (CLA) used in the present invention includes 9,11-octadecadienoic acid, 10,12-octadecadienoic acid and a mixture thereof. 11t / 9t, 11c-
Octadecadienoic acid is preferred. Examples of the form of the conjugated linoleic acid include fatty acids, mono-, di- or triglycerides, sodium salts, potassium salts, calcium salts, phospholipids, lysophospholipids and mixtures thereof, among which fatty acids, triglycerides, phospholipids, calcium salts Is preferred. Further, derivatives of conjugated linoleic acid, such as ascorbic acid derivative, mitomycin C derivative,
Etc. can also be used.

The "antiallergic agent comprising conjugated linoleic acid as an active ingredient" according to the present invention can be used not only as a pharmaceutical but also as an antiallergic food. As an example of a specific embodiment of the antiallergic food, a conjugated linoleic acid-containing oil obtained by subjecting a linoleic acid-containing oil (eg, safflower oil) to an alkali conjugate reaction to convert linoleic acid in the oil or fat to conjugated linoleic acid is obtained. Fat products can be mentioned. The “alkali conjugation reaction” is a reaction in which a fatty acid is isomerized in an alkali-organic solvent solution to convert it into a conjugated fatty acid, and a method using potassium hydroxide as an alkali and ethylene glycol as an organic solvent is known. (J. Am. Oil Chem. Soc.,
36, 631 (1959), 34th Oil Chemistry Symposium Proceedings, p171 (1995), Standard Oil and Fat Analysis Test Method 2.
4.16-17). In addition, the present inventors have previously proposed a method for producing conjugated linoleic acid with improved conversion using propylene glycol as an organic solvent (Japanese Patent Application No. Hei 8 (1996) -108).
-288094). When the raw oil or fat is safflower oil, the CLA content in the conjugated linoleic acid-containing oil or fat obtained by such an alkali conjugation method is generally 10 to 8%.
0%, preferably 50-80%, the remaining components being palmitic acid, stearic acid, oleic acid, unconverted linoleic acid, etc.

When the "antiallergic agent containing conjugated linoleic acid as an active ingredient" of the present invention is used as a medicine, the conjugated linoleic acid can be combined with other components, for example, a medicinal diluent (lactose, starch, etc.). , Tablets, capsules or liquids. When the antiallergic agent according to the present invention is used in any of the above-mentioned foods and medicines, the amount of conjugated linoleic acid to be taken thereby is generally 0.01 to 3% of the weight of the meal, preferably 0.05 to 0.05%. 1%, particularly preferably 0.05 to
0.1%.

The following examples show that conjugated linoleic acid has an antiallergic effect. Example 1 A 4 week old male Sprague-Dawley rat was
After pre-breeding for 1 day, 1.0% linoleic acid group (control group), 0.5% linoleic acid + 0.5% conjugated linoleic acid (hereinafter abbreviated as CLA) group (0.5% CLA group) and 1. 0% CLA group was divided into 3 groups (10 animals in each group).
Experimental food and water were given ad libitum. As shown in Table 2, the composition of the used CLA was 9c, 11t / 9t, 11t.
Two of c-18: 2 and 10t and 12c-18: 2 were the main ones. After breeding for 3 weeks, blood was collected from the abdominal aorta of 5 rats in each group under ether anesthesia, and the organs were immediately removed. Peritoneal exudate cells were collected from the remaining five rats. That is, a rat is sacrificed by ether anesthesia, Tyrode solution is injected into the abdominal cavity, the abdomen is massaged for 2 minutes, the abdomen is opened, the Tyrode solution is collected, the cells are collected by centrifugation, and the number of cells is measured. Diluted to different cell concentrations. The survival rate of the cells was 95% or more, and the ratio of mast cells was about 10%. As a result, there was no significant difference in the amount of food consumed and the amount of weight gain among the three groups.

The release of LTB4 from peritoneal exudate cells upon calcium ionophore stimulation, as shown in FIG.
It tended to decrease depending on the CLA intake. The LTB4 concentration in the spleen decreased depending on the dietary CLA level, and was significantly lower in the 1.0% CLA group than in the control group (FIG. 2). In addition, the concentration of LTB4 and LTC4 in the lung is CL
A was reduced in an intake-dependent manner, and was particularly remarkable in LTC4 (FIG. 3). A significant decrease in serum prostaglandin E2 concentration was observed, albeit mildly, depending on CLA intake (FIG. 4).

The production of immunoglobulin by the mesenteric lymph node lymphocytes is shown in Table 3 as shown in FIG.
G and IgM concentrations were significantly increased depending on CLA intake, and were particularly remarkable in IgG and IgM. The IgE concentration was suppressed, albeit mildly, and significantly decreased particularly in the 1% CLA administration group in the presence of lipopolysaccharide. The immunoglobulin concentration in the serum, as shown in FIG.
The gA and IgM concentrations increased depending on the CLA intake, particularly in the 1% CLA administration group. Furthermore, the IgG concentration significantly increased in the 0.5% and 1% CLA administration groups. Also, the IgE concentration was significantly reduced in the 1.0% CLA group.

From the above results, when rats were fed with CLA, spleen LTB4, lung LTC4 and serum PG were not affected without affecting the food intake or weight gain of rats.
The concentration of E2 is reduced in an addition amount-dependent manner, and the degree of reduction is 1%.
It was remarkable in the CLA group. Production of IgA, IgG and IgM by mesenteric lymph node lymphocytes was significantly increased by CLA intake, and IgE production was decreased. Similar results were obtained for serum immunoglobulin concentrations. These results indicate that CLA exerts an excellent antiallergic effect even in a relatively small amount.

[0015]

[Table 1]

[0016]

[Table 2]

[0017]

[Table 3]

Example 2 Four-week-old Sprague-Dawley male rats were preliminarily reared for one week, and then conjugated linoleic acid (CLA) -free group (control group).
0.05% CLA administration group, 0.1% CLA administration group, 0.
25% CLA administration group, 0.5% CLA administration group and 1.
The rats were divided into a total of 6 groups (5 animals in each group) of the 0% CLA administration group, and were allowed to freely eat the experimental food and water shown in Table 4 for 3 weeks. CL used
The composition of A was 9c, 11t / 9 as shown in Table 5.
t, 11c-18: 2 and 10t, 12c-18: 2
Were the two main ones. Three weeks after the start of feeding, the animals were sacrificed by aortic blood sampling under ether anesthesia, and the organs were immediately removed. As a result, there was no difference between the groups in food intake and body weight gain (Table 6). Further, as shown in Table 7, there was no difference between the groups in the tissue weight.

In this test, the production of immunoglobulins by spleen lymphocytes was measured by focusing on the systemic immune system to which spleen lymphocytes belong. This measurement was performed by culturing spleen lymphocytes for 24 hours and then measuring the immunoglobulin concentration in the supernatant. As a result, as shown in Table 8 and FIG. 6, in the 0.05% CLA administration group, IgA, IgG
And the effect of promoting IgM production was observed.
In the addition group, IgA, IgG and IgM concentrations almost reached a plateau. This result suggests that CLA feeding enhances rat immunity through activation of the antibody-producing system, particularly the systemic immune system to which spleen lymphocytes belong. In addition, it can be seen that even a relatively small amount of CLA, that is, a 0.05% dose, exerts a sufficiently excellent antiallergic effect.

[0020]

[Table 4]

[0021]

[Table 5]

[0022]

[Table 6]

[0023]

[Table 7]

[0024]

[Table 8]

[Brief description of the drawings]

FIG. 1 shows the effect of conjugated linoleic acid on the release of leukotriene B4 from rat peritoneal exudate cells stimulated by the calcium ionophore A23178.

FIG. 2 shows the effect of conjugated linoleic acid on leukotriene B4 and C4 concentrations in rat spleen.

FIG. 3 shows the effect of conjugated linoleic acid on leukotriene B4 and C4 concentrations in rat lung.

FIG. 4. Prostaglandin E in rat spleen and serum
FIG. 3 is a diagram showing the effect of conjugated linoleic acid on the concentration of 2.

FIG. 5 shows the effect of conjugated linoleic acid on the immunoglobulin concentration in rat serum.

FIG. 6 shows the effect of conjugated linoleic acid on immunoglobulin production by rat spleen lymphocytes.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Masaaki Kasai 37-15, Shiomicho, Minato-ku, Nagoya-shi, Aichi Pref. Renoru Oil & Fat Co., Ltd. Nagoya Plant (56) References International Publication 97/32008 (WO, A1) (58) Fields surveyed (Int. Cl. ⁷ , DB name) A61K 31/20 A23L 1/30 A61P 37/02 CA (STN) MEDLINE (STN)

Claims (7)

(57) [Claims] 1. An immunoglobulin modulator comprising conjugated linoleic acid as an active ingredient, which has the effect of increasing the production of immunoglobulins A, G and M and suppressing the production of immunoglobulin E. 2. The immunoglobulin modulator according to claim 1, wherein the conjugated linoleic acid is selected from 9,11-octadecadienoic acid, 10,12-octadecadienoic acid and mixtures thereof. 3. The immunoglobulin modulator according to claim 1, wherein the conjugated linoleic acid is used in the form of a fatty acid, a sodium salt, a potassium salt, a calcium salt, a triglyceride, a phospholipid and a mixture thereof. 4. The immunoglobulin modulator according to claim 1, which is used as a food. 5. The immunoglobulin modulator according to claim 4, which is in the form of an oil or fat product containing conjugated linoleic acid. 6. The immunoglobulin modulator according to claim 5, which is obtained by subjecting safflower oil to an alkali conjugation reaction. 7. The immunoglobulin modulator according to claim 1, which is used as a medicament.