TWI669115B - Antiallergic agent, allergic diarrhea improving agent and pharmaceutical composition - Google Patents

Abstract

An anti-allergic agent suitable for use as an anti-allergic disease and having no side effects, and containing β-type palmitic acid as an active ingredient.

Description

Antiallergic agent, allergic diarrhea improving agent and pharmaceutical composition

The present invention relates to an antiallergic agent, an allergic diarrhea improving agent, and a pharmaceutical composition containing the same.

In modern society, patients with allergic diseases are increasing, and allergic diseases are modern diseases. The main cause of allergic diseases is environmental factors such as dust and dust mites, and factors from food. Once there is an allergic disease, it is forced to live a life that removes allergic factors. As a method for alleviating allergic diseases, there is a drug therapy for administering a drug (Non-Patent Document 1). However, from the viewpoint of side effects, it is not necessarily an effective means.

Most areas of allergic diseases have significant mast cell aggregation and activation. Mast cells express high-affinity receptors for IgE. When specific allergens cause specific IgE production, mast cells will aggregate, resulting in bridging allergen/IgE mast cell bridging and degranulation, and inflammatory mediator separation (1st) (a) Figure ~ Figure 1(b)).

Non-patent literature

Non-Patent Document 1: "Knowledge of easy-to-understand medicines - knowing how to use them, how to use medicines", edited by Ninomiya, and new Japanese regulations, issued on March 22, 2007, pp. 379-395

It is an object of the present invention to provide an antiallergic agent which improves allergic diseases and has no side effects.

The inventors of the present invention have carefully examined and found that the palmitic acid (hereinafter referred to as β-palmitic acid) having a β-position bonded to a glyceride has an antiallergic action, particularly an allergic diarrhea, and has completed the present invention.

That is, the present invention is as follows.

(1) An antiallergic agent containing β-type palmitic acid as an active ingredient.

(2) An agent for improving allergic diarrhea, which contains β-type palmitic acid as an active ingredient.

(3) A pharmaceutical composition comprising the antiallergic agent according to (1) or the allergic diarrhea as described in (2).

(4) An additive for preventing or treating allergy, which contains β-type palmitic acid as an active ingredient.

(5) An oral composition for preventing or treating allergy, which comprises the additive described in (4).

Beta-type palmitic acid is contained in specific edible fats and oils such as lard from pigs, which can suppress the production of allergen-specific IgE in allergic diseases, reduce the number of large intestine mast cells, and inhibit the degranulation of mast cells. effect.

Therefore, the anti-allergic agent or the allergic diarrhea improving agent of the present invention containing β-type palmitic acid as an active ingredient can be applied to safety and side effects. A pharmaceutical composition which has little anti-allergic action or an allergic sputum improvement effect and an oral composition for preventing or treating allergy.

And, although beta-type palmitic acid is known to strengthen the bones of young children or change In addition to the anti-allergic effect of the intestinal flora, the function of the anti-allergic itself is first known to the inventors.

Fig. 1(a) to Fig. 1(c) show the mechanism of aggregation and activation of mast cells in the site of allergic diseases.

Fig. 2 is a view showing the results of observing the incidence of allergic diarrhea by administering vegetable oils (test fats and oils) having an increased ratio of soybean oil, vegetable fat or beta palmitic acid.

Figures 3(a) to 3(c) show the analysis of vegetable oils (Soy0.4+) with improved ratio of soybean oil (Soy4), vegetable oil (Soy0.4+Cont3.6) or β-palmitic acid. Beta 3.6), the effect of allergic diarrhea (the amount of allergen-specific IgE production, the number of large intestinal mast cells, and the number of degranulated mast cells).

The β-type palmitic acid which is an active ingredient of the present invention means all the chemicals The same compound. In addition, it is not only a pure product of β-type palmitic acid, but also a mixture with other substances. For example, β-type palmitic acid can be measured by a known measurement method, and the raw material present therein can be used as it is.

As a raw material rich in β-type palmitic acid, it can be representative of the utensils. For lard. On the other hand, lard has a unique odor. In order to solve this problem, it is known that the palmitic acid-rich vegetable oil is chemically modified or modified to obtain a β-type palmitic acid-rich raw material (Japan). Special Report No. 8-509620, Japan Japanese Patent Publication No. Hei 8-509621 and Japanese Patent Application Laid-Open No. Hei 6-70786. In addition, for example, Betapol (Loders Croklann) is commercially available and can be purchased directly or blended with other suitable materials.

When the mixture of the foregoing and other substances contains β-type palmitic acid, It is preferable to contain 10% or more of β-type palmitic acid, preferably 20 to 90%, more preferably 30 to 80%, particularly preferably 40 to 70%, and most preferably 50 to 60%. The fatty acid composition has a β-type palmitic acid content of 10% or more, and a sufficient antiallergic effect can be obtained.

Beta-type palmitic acid is finally administered to the body by mouth, by the tube or by the intestines. The method of absorption, the manner of ingestion thereof is not particularly limited, but oral ingestion is preferred.

The recommended daily intake of β-palmitic acid is preferably 0.1g~100g. It is preferably 0.2 g to 80 g, more preferably 0.4 to 60 g, more preferably 0.6 to 50 g, still more preferably 0.8 to 40 g, more preferably 1.2 to 30 g, and particularly preferably 1.6 to 20 g, preferably 2~10g.

In addition, via the demonstration of the examples, the recommended intake of beta palmitic acid The frequency is continuous intake, and a better anti-allergic effect can be expected. It is preferably 2 or more times, preferably 3 times or more, more preferably 4 times or more, more preferably 5 times or more, and particularly preferably 6 times. The above is preferably 7 or more times. These can be in the form of 1 package each time.

Beta-type palmitic acid and raw materials containing these as raw materials without side effects The material can be widely used as an antiallergic agent and an allergic diarrhea improving agent, or a pharmaceutical composition containing the same or an oral composition for preventing or treating allergy.

Antiallergic agent or allergic diarrhea improving agent of the invention, β type brown a combination of palmitic acid or such pharmaceutically compatible pharmaceutical carrier, orally or via The method is to give a mammal containing humans.

Anti-allergic agent or allergic diarrhea improving agent of the present invention The administration unit of the drug preparation is not particularly limited, and for the purpose of the treatment, a general use in a usual preparation can be appropriately selected. Here, in particular, a lozenge, a pill, a powder, a liquid, a suspension, an emulsion, a granule, a fine granule, a capsule, a medicated syrup, an elixir, a suppository, an injection, an ointment may be optionally used. Agents, patches, eye drops, nose drops, etc. Moreover, when such a case is used, the preparation can be administered according to a usual method.

The anti-allergic agent or the allergic diarrhea improving agent of the invention is prepared When the pharmaceutical preparation (formulation) is prepared, the preparation carrier is not particularly limited, and a general-purpose preparation can be selected in accordance with the purpose of the preparation. Here, specifically, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a fluidity promoter, a flavoring agent, a flavoring agent, a coloring agent, a fragrance, a diluent, a surfactant, or the like may be optionally used. And additives such as solvents for injections. Moreover, when such a use is used, the preparation can be produced according to a usual method.

As the binder, for example, starch, dextrin, gum arabic, Gelatin, hydroxypropyl starch, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol, and the like.

Examples of the disintegrator include starch, hydroxypropyl starch, and carboxymethyl Cellulose sodium, potassium carboxymethylcellulose, carboxymethylcellulose and low substituted hydroxypropylcellulose.

As the surfactant, for example, sodium lauryl sulfate, soybean Lecithin, sucrose fatty acid esters and polysorbates.

As the lubricant, for example, talc, wax, hydrogen added plants Oil, sucrose fatty acid ester, magnesium stearate, potassium stearate, aluminum stearate and polyethylene glycol.

Examples of the fluidity promoter include light anhydrous citric acid, dried aluminum hydride rubber, synthetic aluminum ruthenate, and magnesium ruthenate.

The content of the β-type palmitic acid of the present invention is not particularly limited, and can be appropriately selected in accordance with the effects and effects of the present invention. Here, for example, the daily recommended amount of β-type palmitic acid in the usual preparation is preferably 0.1 to 100 g, preferably 0.2 to 80 g, more preferably 0.4 to 60 g, still more preferably 0.6 to 50 g, and still more. Good 0.8~40g, and even better 1.2~30g, especially good 1.6~20g, best 2.0~10g.

The pharmaceutical composition is, for example, a pharmaceutical product or a pharmaceutical product, and is not particularly limited as long as it can expect the effects and effects of the present invention.

As an oral composition for preventing allergies or treating allergies, for example, supplements, infant formula milk powder, peptide milk powder, larger infant milk powder, developmental milk powder, low birth weight infant formula milk powder, lactose-free milk powder, The oral composition for preventing allergies or treating allergy for infants and young children, such as low-sodium special milk powder and powder for breast-feeding, is not particularly limited as long as the effect and efficacy of the present invention can be expected.

In particular, when beta-type palmitic acid is used for the prevention or treatment of allergic oral compositions for infants and young children, such as infant formula, it is possible to suppress allergic diarrhea in infants and children, and to expect effective growth of infants and young children.

In addition, when the β-type palmitic acid is used as an oral composition for preventing or treating allergies for infants and young children, such as infant formula, the addition of a component other than β-palmitic acid is not particularly limited.

For example, an appropriate amount can be allocated to promote the development or growth of infants and young children. When hexahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (ARA), and cholesterol are used to prepare a milk powder for infants and young children supplemented with β-type palmitic acid It can inhibit allergic diarrhea in infants and young children, and can expect effective development and growth of infants and young children.

In addition, manufacture and provide a beta-milk that removes or reduces allergenicity Addition of globulin to β-palmitate infant formula, appropriate amount of nucleoside or nucleotide with immunomodulatory function, added β-palmitate infant formula, or no soy lecithin as emulsifier When adding β-type palmitic acid infant formula, it can suppress allergic diarrhea in infants and young children, and it can be expected to effectively prevent allergies caused by different allergens in infants and young children.

Furthermore, manufacturing and providing enhanced milk coagulation with prophylaxis Adding β-type palmitic acid infant formula to lactadherin, and adding β-type palmitic acid infant with at least one of intensive immune fructose, nucleoside or nucleotide, taurine and zinc When children formula milk powder, they can suppress allergic diarrhea in infants and young children, and can expect to effectively strengthen the immunity of infants and young children.

Furthermore, it produces and provides selective decomposition of beta that is not easily digested and absorbed. Adding β-type palmitic acid to infants and young children to prepare milk powder, and enhancing the addition of α-lactalbumin, which is highly digestible, can inhibit allergic diarrhea in infants and young children when adding β-palmitic acid infant formula. It can be expected to effectively improve the digestion and absorption of the intestines of infants and young children.

Furthermore, manufacturing and providing the right amount of preparation to promote proper intestinal flora The addition of fructooligosaccharides, nucleosides or nucleotides to the addition of β-palmitic acid infant formula milk powder, and the proper amount of lactose added to promote the formation of proper intestinal flora can be inhibited when adding β-type palmitic acid infant formula Allergic diarrhea in infants and young children, and can be expected Effectively improve the convenience of infants and young children.

In this manual, infants and young children include infants and young children, in detail, It includes babies, toddlers and newborns, and more specifically, infants, young children, newborns, premature babies and low birth weight infants. In the present specification, the species of infants and young children is not particularly limited and includes humans.

Infants refer to children in infancy, infancy refers to breast milk, etc. The period when milk is the main source of nutrition. In the case of humans, it usually refers to an infancy less than one year old. Children refer to children until the time they are in school. Neonate refers to a child in the neonatal period, and the neonatal period refers to the period after birth, taking humans as an example, usually in the neonatal period after birth to within 4 weeks.

Adding beta-type palmitic acid supplement as long as it is beta-type palmitic acid The form to be ingested is not particularly limited in its form or form, and examples thereof include a powder form, a liquid form, a paste form, a tablet form, and a solid shape.

Any substance other than β-palmitic acid can be arbitrarily designed according to individual design By blending (adding), the effect and performance of the present invention are enhanced by adding materials or the like for the supply having known functional properties, and the effect and performance of the addition can be expected. As the material for the supplement, known materials such as minerals, vitamins, proteins, carbohydrates (for example, dietary fiber, etc.), lipids, microorganisms or their metabolites may be used alone, or a plurality of them may be used in combination or All used in combination.

For example, blending an appropriate amount of functional material with intestinal function, for example The addition of β-type palmitic acid supplement to the fermentation composition of oligosaccharide, dietary fiber, lactic acid bacteria, Bifidobacterium and propionic acid bacteria can be expected to suppress or treat allergies, and at the same time effectively alleviate or inhibit constipation or diarrhea. In addition, for example, a β-type palmitic acid supplement supplemented with an appropriate amount of calcium or vitamin D can be expected to inhibit or treat allergies, Effective prevention or treatment of osteoporosis.

Also, the supplies here are not just in the pharmacy or chain pharmacy. There is no particular limitation on the narrow-supply supplements that are sold as long as they are replenished to the body for the purpose of nutritional supplement, nutritional adjustment, or maintenance of regularity.

In addition, it may also be a type β palm using the active ingredient of the present invention. Acid is used as an additive for the prevention of allergies or for the treatment of allergies. For example, it can be used as an additive in a predictable food or drink that does not have side effects in a pharmaceutical composition or dietary knowledge, or a composition for preventing allergy or treating allergy, and can be ingested orally or via a tube.

The β-type palmitic acid which is an active ingredient of the present invention is not limited to humans. The above-mentioned excellent effects and effects can also be exhibited for mammals (mammals). Therefore, the present invention is also a feed and feed additive containing β-type palmitic acid as an active ingredient, particularly a mammalian milk powder for feeding and a milk powder additive.

Example

Hereinafter, the experimental results of the examples and comparative examples relating to the present invention will be enumerated, and the present invention will be described in more detail. Moreover, the invention is not limited to the embodiments.

Soybean oil, 90% by mass of soybean oil, which is replaced by the "plant fat" shown in Table 1, or 90% by mass of soybean oil, as shown in Table 1, "transesterification by enzyme to increase the ratio of beta palmitic acid. The composition lipids substituted with the vegetable oils and fats (experimental oils and fats) were added to the following purified feeds at 4% by mass to prepare feed 1, feed 2, and feed 3, and the 6-week-old mice were continuously ingested for 2 months ( The group of mice that ingested feed 1 was used as a soybean oil group, the group of mice that ingested feed 2 was used as a plant oil group, and the group of mice that ingested feed 3 was used as a test oil. Lipid group).

This refined feed is based on AIN-93M (maintenance) for the United States. The standard feed for mice or rats used for feeding nutrition research published by the Institute of Nutrition (AIN) in 1993. Specifically, it contains 46.5692% by mass of corn starch, 14.0% by mass of milk caseins, 15.5% by mass of pregelatinized corn starch, 10% by mass of granulated sugar, 4.0% by mass of refined soybean oil, and cellulose powder. 5.0% by mass, mineral mixture (AIN-93-MX) 3.5% by mass, vitamin mixture (AIN-93VX) 1.0% by mass, L-cystine 0.18% by mass, tartaric acid choline 0.25% by mass, tert-butyl group Hydroquinone was 0.0008 mass%.

Also, in the composition of Table 1, the main fatty acid of triglyceride The composition is calculated in terms of area % based on the reference oil analysis method tentatively 17-2007 (capillary gas chromatography). Further, the β-type palmitic acid composition was analyzed using Candida Antarctica lipase B immobilized enzyme Novozymes 435 (manufactured by Novozymes Co., Ltd.), and the 2-position monoglyceride was fractionated, and the palmitic monoglyceride at the 2-position was analyzed by a gas-liquid gas chromatograph. In addition, the bonding ratio of the β-position in the whole palmitic acid was calculated by [the fatty acid content of the palmitic acid monoglyceride/(palmitate triglyceride content × 3)] × 100 [%].

After 2 months of ingesting the individual feeds, Mice bred from 1 to 3 were subjected to systemic sensitization with 1 mg of egg white (OVA) using Freund's complete adjuvan, starting at 1 week after systemic sensitization began. The frequency of the second dose was orally administered to 50 mg of OVA. Thereby, allergic diarrhea was induced, and the symptoms were observed by using the sputum observed at 30 minutes to 60 minutes from the start of oral administration as an index. The result is shown in Fig. 2.

As shown in Figure 2, after the fourth oral vote, confirm Compared with the other two groups, the experimental oil and fat group has a lower incidence of allergic diarrhea. From this result, it is known that β-type palmitic acid has an antiallergic effect and is effective for improving allergic diarrhea.

Next, in order to investigate the incidence of beta palmitic acid and allergic diseases In the correlation between various factors, soybean oil, vegetable oil, or vegetable oil and fat which increases β-type palmitic acid were used, and the amount of allergen-specific IgE production, the number of large intestinal mast cells, and the number of degranulated cells of mast cells were analyzed in the following order.

After 2 months of ingesting the individual feeds, The mice bred from 1 to 3 were treated with Freund's complete adjuvant and 1 mg of egg white (OVA). Systemic sensitization was carried out, and after 1 week from the start of systemic sensitization, 50 mg of OVA was orally administered at a frequency of 3 times per week. On the next day of oral administration of these OVAs 7 times, serum was recovered, and the amount of IgE specific to OVA [Fig. 3(a)], the number of degranulated mast cells (mMCP-1) [Fig. 3(c)] , DS mouse IgE ELISA (OVA) (DS Pharma Biomedical) and Mouse MCPT-1 (mMCP-1) ELISA Ready-SET-Go! (Affymetrix) Determination. In addition, the number of mast cells is measured by collecting the mononuclear sphere from the lamina propria of the large intestine [Fig. 3(b)]

As shown in the third (a) to the third (c), the incidence of allergic diarrhea in Fig. 2 was correlated, and it was confirmed that the experimental oil and fat group was reduced compared with the other two groups. From this result, it is understood that β-type palmitic acid inhibits the production of allergen-specific IgE in allergic diseases, reduces the number of large intestinal mast cells, and inhibits the degranulation of mast cells.

Industrial utilization

Since the antiallergic agent or the allergic diarrhea improving agent of the present invention is used, it is expected that prevention or treatment of an allergic disease can be achieved without side effects. In particular, when the antiallergic agent of the present invention is applied to an oral composition for preventing allergy or treating allergy for infants, it can prevent allergic diarrhea in infants, and from the viewpoint of effectively developing or growing infants, To be effective.

While the invention has been described with respect to the specific embodiments of the present invention, it will be understood In addition, this case is based on the Japanese franchise application (Japanese Patent Application No. 2014-106059) filed on May 22, 2014, and all of them are used for this.

Claims (5)

An antiallergic agent containing β-type palmitic acid as an active ingredient, wherein the content of β -type palmitic acid in the fatty acid composition is 10% or more. An agent for improving allergic diarrhea, comprising β-type palmitic acid as an active ingredient, wherein the content of β -type palmitic acid in the fatty acid composition is 10% or more. A pharmaceutical composition comprising an anti-allergic agent according to claim 1 or an allergic diarrhea improving agent according to item 2 of the patent application. An additive for preventing or treating allergy, comprising β-type palmitic acid as an active ingredient, wherein the content of β -type palmitic acid in the fatty acid composition is 10% or more. An oral composition for preventing or treating allergy, which is an additive added in the fourth item of the patent application.