JP2009249323A - Antihistamine composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antihistamine composition that is safe, has no harmful action and can be continuously ingested. <P>SOLUTION: The antihistamine composition comprises a wheat protein hydrolyzate. The composition comprises the antihistamine composition and prevents and/or ameliorates allergic diseases. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an antihistamine composition containing a hydrolyzate of wheat protein, and a composition for preventing and / or improving allergic diseases containing the same.

  In recent years, allergic diseases are one of the diseases with the highest incidence in developed countries, and typical examples include hay fever, allergic conjunctivitis, bronchial asthma, and atopic dermatitis. Among them, it is said that the number of patients suffering from hay fever is about 20 million in Japan alone, and the number of people who develop the disease increases year by year, which is a serious social problem.

  Hay fever directly involves allergen-specific IgE antibodies overproduced from B cells, histamine and leukotrienes released from mast cells and basophils, or a Th1 / Th2 balance bias toward the Th2 side. It is known that That is, the allergen that has entered the body is taken up by the antigen-presenting cells and decomposed, and a part of the information is presented to the T cells. The T cells that have received the antigen are differentiated and activated into Th2 cells, and produce cytokines such as IL-4 to activate the B cells. Activated B cells produce IgE antibodies specific for allergens, and these IgE antibodies bind to Fcε receptors present on the surface of mast cells and basophils. When the allergen enters the body again and bridges IgE antibodies on the surface of mast cells or basophils, a large amount of chemical mediators such as histamine are released from the cells, and leukotrienes are synthesized on the cell surface. These substances increase vascular permeability and cause edema and nasal secretion, and contract the smooth muscles and cause airway contraction. On the other hand, it is becoming clear that the Th1 / Th2 balance is chronically biased toward the Th2 side due to changes in lifestyle and dietary habits in recent years, contributing to an increasing tendency of allergic diseases.

  Currently, methods for improving the symptoms of hay fever include reducing the chance of contact with pollen using a mask, goggles and air purifier, cleaning pollen adhering to mucous membranes such as the nose, and free histamine. To suppress allergic reaction with antihistamines that inhibit the binding of receptors, degranulation inhibitors with cell membrane stabilization, or leukotriene synthesis inhibitors, etc., as well as immunization by regularly injecting allergens themselves There is a desensitization therapy that induces tolerance. However, pollen scattering varies depending on the place and date and time, and it is very difficult to carry out the above method in a timely manner according to the onset. On the other hand, side effects such as drowsiness and malaise are regarded as problems with antihistamines, and there are limits to daily and continuous administration. In addition, many foods and functional foods that have an effect on hay fever are commercially available (see, for example, Patent Documents 1 and 2). However, these foods cannot be said to have sufficient effects, and both are decisive. Not. Therefore, a functional food that can be taken on a daily basis and that can effectively relieve symptoms such as hay fever is desired.

  By the way, wheat, which is a raw material for staple foods such as bread and noodles, is an excellent food that can be eaten continuously almost every day, and attempts have been made to obtain functional components from this wheat. For example, Patent Document 3 discloses an anti-fatigue composition comprising a wheat gluten hydrolyzate. Patent Document 4 discloses that a peptide having a specific amino acid sequence contained in a wheat gluten hydrolyzate has an immunostimulatory action. However, it has not been known so far that a hydrolyzate of wheat protein suppresses an abnormal immune reaction and alleviates allergic diseases by antihistamine action.

JP 2006-335647 A JP 2007-182403 A JP-A-2005-97162 JP 2005-97223 A

  It can be ingested safely and easily on a daily basis, and has a remarkable antihistaminic action, such as various allergic diseases such as hay fever, allergic conjunctivitis, bronchial asthma, atopic dermatitis, etc. There is a great demand for natural materials effective for prevention and / or improvement. Accordingly, an object of the present invention is to provide a composition having an antihistaminic action that is safe and has no harmful action and can be taken continuously.

  As a result of intensive studies to solve the above problems, the present inventors have found that a hydrolyzate of wheat protein, preferably a hydrolyzate of wheat gluten, more preferably 15 to 60% by mass of L-glutamine derived from wheat. And peptides having an average molecular weight of 200 to 100,000 dalton have a very strong antihistamine effect and are useful for the prevention and / or improvement of various allergic diseases.

That is, the present invention relates to the following matters.
(1) An antihistamine composition containing a hydrolyzate of wheat protein.
(2) A composition for preventing and / or improving an allergic disease comprising the antihistamine composition according to (1).
(3) The composition according to (2), wherein the allergic disease is hay fever.
(4) The composition according to any one of (1) to (3), comprising a wheat gluten hydrolyzate as a wheat protein hydrolyzate.
(5) The wheat protein hydrolyzate according to any one of (1) to (4), comprising a peptide having an L-glutamine content of 15 to 60% by mass and an average molecular weight of 200 to 100,000 daltons. Composition.

  According to the present invention, it can be ingested safely and conveniently on a daily basis, and has a remarkable antihistamine action, and has various allergenic properties such as hay fever, allergic conjunctivitis, bronchial asthma, and atopic dermatitis. A composition effective for preventing and / or ameliorating a disease is provided.

Hereinafter, preferred embodiments of the present invention will be specifically described.
In the present invention, the antihistamine action refers to various adverse effects caused by binding of histamine to the histamine receptor, such as itchy eyes, itchy skin, mucous itching, cough, sneezing, nasal discharge, nasal congestion, It refers to the action of preventing, treating, reducing or alleviating excessive eyes and the like. Furthermore, it also includes the action of preventing, treating, reducing or alleviating various symptoms caused by histamine caused by smooth muscle contraction, increased vascular permeability, neutrophil migration, platelet aggregation and the like. The antihistamine action should be measured by a known method such as a method for measuring the amount of histamine released from histamine-free cells represented by mast cells, a histamine receptor binding test, an activation test for histamine receptor-expressing cells. Can do.

  The antihistamine composition of the present invention is characterized by containing a hydrolyzate of wheat protein as an active ingredient. Wheat is one of the few foods that can be eaten daily in the form of bread, noodles, etc. as a staple food, and is eaten all over the world. The wheat protein hydrolyzate of the present invention is safe and simple. Can be taken on a daily basis.

  The present invention also relates to a composition for preventing and / or ameliorating allergic diseases comprising the antihistamine composition. The composition is also composed of a hydrolyzate of wheat protein as an active ingredient, and can be ingested safely and easily on a daily basis. In addition, hay fever, allergic conjunctivitis, bronchial asthma, atopic It is effective in preventing and / or improving various allergic diseases such as dermatitis.

  The wheat protein hydrolyzate of the present invention is obtained by hydrolyzing a high molecular weight wheat-derived protein into a peptide having a relatively low molecular weight, thereby obtaining the action of the present invention. Therefore, any wheat protein hydrolyzate can exert the effect of the present invention, but preferably a composition containing a peptide having a specific amino acid content and a specific molecular weight (peptide mixture). Therefore, a higher effect can be expected.

  Any wheat can be used as long as it is available. Preferable examples include cereal wheat genus bread wheat, durum wheat, crab wheat, spelled wheat and enma wheat, etc., and Aegilops talho wheat and wedge wheat.

  The wheat protein used for hydrolysis in the present invention mainly refers to gluten, but may also contain other proteins known to be contained in wheat such as albumin, globulin, glutenin, and gliadin. Moreover, impurities such as starch and fibers may be inevitably contained. In the present invention, wheat protein that has been subjected to chemical treatment or biological treatment with an enzyme or the like in advance to reduce molecular weight or that has increased affinity with protease can be used as wheat protein. . Furthermore, unpurified wheat protein, unrefined wheat gluten and the like can be used. When starch is purified from wheat, wheat protein is obtained as a by-product. However, this may be used as it is, and by doing so, a by-product wheat protein that has not been conventionally used can be effectively used.

  The hydrolyzate of wheat protein may be any one as long as it is obtained by hydrolyzing the above wheat protein. Hydrolysis may be carried out by a known method, for example, a method of hydrolyzing with an acid, A method of hydrolyzing using a hydrolase (protease) can be applied.

  As a method for hydrolyzing wheat protein using an acid, a conventional method can be adopted. For example, as the acid, mineral acids such as sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid and sulfurous acid; organic acids such as oxalic acid, citric acid, acetic acid and formic acid can be used. As a procedure for hydrolyzing wheat protein using such an acid, an acid is added to an aqueous medium containing wheat protein so that the acid normality is in the range of 0.01 to 2 normal, and the temperature of the aqueous medium is adjusted. Examples include a procedure of hydrolyzing at 50 to 100 ° C. for 10 minutes to 6 hours. When it is desired to stop the hydrolysis, it can be stopped by adding a base and neutralizing.

  When hydrolyzing with an acid, the concentration of wheat protein in the aqueous medium needs to be adjusted appropriately depending on the type and normality of the acid, but it is usually better to treat the protein at 1.0 to 80% by mass. .

  Examples of a method for hydrolyzing wheat protein using a protein hydrolase include a method of hydrolyzing wheat gluten using a protease or a protease and amylase (Japanese Patent No. 2010439 and Japanese Patent No. 2985193). See the official gazette). Examples of the protease include various proteases such as pepsin, trypsin, chymotrypsin, acid protease derived from Hilotake, acid protease derived from Aspergillus, papain, bromelain, thermolysin, trypsin, chymotrypsin, pronase, subtilisin, and esperase. Can be used. A single protease may be used, a plurality of types may be combined, for example, an acidic protease and a neutral protease may be used in combination, or the treatment may be performed a plurality of times.

  When wheat gluten is hydrolyzed with protease, if amylase is used in combination, impurities such as starch and fiber contained in wheat gluten are decomposed and removed, resulting in a high yield of hydrolyzate containing peptide components with high purity. (See Japanese Patent No. 2985193). Wheat gluten is insoluble in water and inferior in water dispersibility, but wheat gluten hydrolyzate is excellent in water dispersibility because of its low molecular weight.

  The wheat protein hydrolyzate thus obtained may be used as it is as an active ingredient in the present invention. Therefore, in addition to the peptide component, the wheat protein hydrolyzate of the present invention may contain other components and enzymes derived from wheat protein and wheat gluten that are inevitably included in the production process.

  However, in view of ease of handling, storage stability, etc., it is preferable to remove insolubles from the hydrolyzate and further remove moisture to obtain a solid form. This insoluble matter removal and moisture removal may be performed by any method as long as the obtained hydrolyzate does not cause denaturation or thermal decomposition. For example, filtration, centrifugation, centrifugal filtration, spray drying, Any method such as spray cooling, drum drying, vacuum drying, freeze drying and the like can be used. Alternatively, after binding or supporting the water-soluble component to an appropriate carrier, the solvent can be removed by the method as described above to obtain a solid.

  As the hydrolyzate of wheat protein of the present invention, a commercially available product (for example, “Glutamine Peptide GP-1” manufactured by Nisshin Pharma Co., Ltd.) may be used as it is, and in some cases, this may be used as a raw material. Further, it may be used after being subjected to treatments such as hydrolysis and fractionation.

  A preferred embodiment of the wheat protein hydrolyzate of the present invention is a peptide (peptide mixture) having an L-glutamine content of at least 15% by mass and an average molecular weight of 200 to 100,000 daltons.

  When the L-glutamine content in the hydrolyzate of wheat protein is 15% by mass or more, the effect is high and the intake can be relatively suppressed. The upper limit of the L-glutamine content is not particularly limited, but is 60% by mass or less from the standpoint of availability and ease of preparation and economy because preparation from a natural protein is easy if it is 60% by mass or less. Is preferred. Therefore, the L-glutamine content of the peptide contained in the hydrolyzate of wheat protein is preferably 15 to 60% by mass, more preferably 20 to 40% by mass. The L-glutamine content in the wheat protein hydrolyzate can be calculated based on the amide nitrogen-containing L-amino acid content determined from the amide nitrogen content measured by the amide nitrogen substitution method. .

  If the average molecular weight of the hydrolyzate of wheat protein is 200 daltons or more, the taste is good without exhibiting a bitter taste. If the average molecular weight is 100,000 daltons or less, the water solubility is not lost, It is easy to handle without forming a viscous mass when added. The average molecular weight of the hydrolyzate of wheat protein is not particularly limited as long as it is 200 to 100,000 daltons, but is preferably 500 to 80,000 daltons, and more preferably 1,000 to 60,000 daltons. It is more preferably 2,000 to 50,000 daltons, and most preferably 3,000 to 40,000 daltons.

  The average molecular weight of the hydrolyzate of wheat protein referred to in this specification is an average molecular weight as measured by gel filtration, and details thereof are as described in the Examples section below. If the hydrolyzate of wheat protein used in the present invention has an L-glutamine content of at least 15% by mass, the types of amino acids other than L-glutamine and the composition ratio thereof are not particularly limited.

  A hydrolyzate of wheat protein is derived from wheat with experience of eating and is composed of L-amino acids constituting natural proteins, so that it is excellent in terms of safety to humans and animals, and is easy to obtain and prepare. From the viewpoints of properties and economy.

  Wheat gluten usually contains 25-50% by weight of L-glutamine, so it hydrolyzes wheat gluten under conditions such that the average molecular weight is in the range of 200-100,000 daltons, and if necessary By performing fractionation or the like, a peptide having an L-glutamine content of 15 to 60% by mass and an average molecular weight of 200 to 100,000 daltons can be obtained relatively easily.

  The antihistamine composition of the present invention and the composition for preventing and / or ameliorating allergic diseases (hereinafter, both may be referred to as the composition of the present invention) are the hydrolyzate of wheat protein. It is administered in the range of 1 to 40 g per day on the basis of dry mass. A typical daily dose is 6-10 g. However, the wheat protein hydrolyzate used in the present invention is a highly safe product derived from natural products, and its dosage can be further increased. It is desirable to increase or decrease the dosage as appropriate while observing the effects. Although the daily dose can be administered or ingested once, it is desirable to administer the dose in several divided doses.

  The composition of the present invention is characterized in that it contains a hydrolyzate of wheat protein obtained by the above-mentioned process, but it is used alone or in various forms such as a pharmaceutical composition and a food composition. When continuously ingested or applied continuously in the form of a cosmetic composition, systemic or local antihistamine action is exhibited, and various allergic diseases such as hay fever, allergic conjunctivitis It is useful for prevention and / or improvement of bronchial asthma, atopic dermatitis and the like.

  Moreover, since the composition of the present invention uses safe wheat as a raw material, it is highly safe and has a good flavor, so it can be taken orally enough as it is, and can be applied as a cosmetic composition. Long-term continuous administration is possible. Furthermore, continuous intake over a long period of time is easy as various pharmaceutical compositions and food compositions.

  At that time, the hydrolyzate of wheat protein obtained by the above-mentioned process can be used alone as it is, but as long as the effect of the present invention is not impaired, additives described later, other known antihistamines, antiallergy You may mix | blend a substance, an immunomodulating substance, etc. individually or in combination.

  Examples of dosage forms when the composition of the present invention is used as a pharmaceutical composition include tablets, capsules, granules, powders, syrups, dry syrups, liquids, suspensions, and other oral preparations, inhalants, and suppositories. Enteral preparations such as preparations, ointments, creams, gels, external preparations for skin such as patches, drops, injections and the like. Of these, oral agents are preferred.

  The composition of such a dosage form includes additives conventionally used for the hydrolyzate of wheat protein as an active ingredient, such as excipients, disintegrants, binders, lubricants, surfactants, alcohols, Water, a water-soluble polymer, a sweetener, a corrigent, a sour agent and the like can be blended according to the dosage form, and can be formulated according to a conventional method. Liquid preparations such as liquids and suspensions may be dissolved or suspended in water or other appropriate media immediately before taking, and in the case of tablets and granules, the preparations may be prepared by well-known methods. The surface may be coated.

  The content of the hydrolyzate of wheat protein in the pharmaceutical composition according to the present invention varies depending on the dosage form, but is usually 0.001 to 99% by mass, preferably 0.01 to 80% based on the dry mass. It is desirable that the dosage is in a mass% range so that the daily dose can be controlled so that the above-mentioned daily intake for adults can be taken.

  When the composition of the present invention is prepared as a food composition, the form is not particularly limited, and all of the wheat protein hydrolyzate of the present invention can be blended in addition to health food, functional food, food for specified health use, etc. Of food. In the present invention, the food includes beverages. Specifically, various preparation forms such as liquid foods such as tablets, chewable tablets, powders, capsules, granules, drinks, and enteral nutrients can be used. The food composition in the form of a preparation can be produced in the same manner as the pharmaceutical composition. Furthermore, the food composition includes tea drinks such as green tea, oolong tea and black tea, soft drinks, jelly drinks, sports drinks, milk drinks, carbonated drinks, fruit juice drinks, lactic acid bacteria drinks, fermented milk drinks, powdered drinks, cocoa drinks, purified water, etc. Beverages, butter, jam, sprinkles, margarine spreads, mayonnaise, shortening, custard cream, dressings, breads, cooked rice, noodles, pasta, miso soup, tofu, milk, yogurt, soup or sauces, confectionery ( For example, it may be prepared as biscuits, cookies, chocolate, candy, cake, ice cream, chewing gum, tablet) or the like.

  The food composition further includes other food materials used in the production of food and feed, various nutrients, various vitamins, minerals, amino acids, various fats and oils, various additives (for example, flavoring ingredients, sweeteners, organic acids, etc. And sour agents, surfactants, pH adjusters, stabilizers, antioxidants, dyes, flavors, etc.) and the like, and can be produced according to a conventional method. Moreover, the food composition which concerns on this invention can also be manufactured by mix | blending the hydrolyzate of the wheat protein of this invention with the food normally eaten.

  In the food composition according to the present invention, the content of the hydrolyzate of wheat protein varies depending on the form of the food, but is usually 0.001 to 80% by mass, preferably 0.01 to 0% based on the dry mass. It is 50 mass%, More preferably, it is the range of 1-50 mass%. The daily intake may be taken once, but may be taken in several divided doses. It is preferable that the intake amount per day can be managed so that the intake amount per day for an adult can be consumed.

  The food composition includes not only food for humans but also feed for livestock, racehorses, pet food, and the like. Since the feed is almost the same as the food except that the subject is an animal, the description regarding the food in the present specification can be similarly applied to the feed.

  Since the composition of the present invention has high safety, it can also be prepared as a cosmetic composition. Since the cosmetic composition according to the present invention can be continuously applied, it is particularly effective for preventing and / or improving atopic dermatitis.

  When preparing a cosmetic composition, the wheat protein hydrolyzate may be used as it is as a cosmetic composition, or the cosmetic raw material and the wheat protein hydrolyzate are blended by a general-purpose method to obtain a milky lotion, a cosmetic liquid, Cream, lotion, essence, pack and sheet, foundation, funny, blusher, lipstick, eye shadow, eyeliner, mascara, facial cleanser, skin cleanser, gel, gel, skin cleanser, body shampoo, etc., shampoo Cosmetic compositions in the form of hair cosmetics such as rinses, hair treatments, hair nourishing agents, bath preparations, ointments, quasi drugs, oil blotting paper, and the like may be prepared.

  The cosmetic composition according to the present invention includes, in addition to the hydrolyzate of wheat protein, conventionally known excipients and fragrances according to the desired dosage form, fats and oils, surfactants, preservatives, metal ions. Add appropriate ingredients such as sequestering agents, water-soluble polymers, thickeners, pigments, UV protection agents, moisturizers, antioxidants, pH regulators, detergents, desiccants, emulsifiers, etc. Can be manufactured.

  The content of the hydrolyzate of wheat protein in the cosmetic composition according to the present invention is not particularly limited, but is usually 0.001 to 80% by mass, preferably 0.01 to 50% by mass, based on the dry mass. Is within the range.

  The composition of the present invention can be combined with known antihistamines, antiallergic substances, and immunomodulators. Antihistamines include tea, perilla, bursa, polyphenols, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, diphenylpyraline teolurate, clemastine fumarate, chlorpheniramine maleate, triprolidine hydrochloride, cyproheptadine hydrochloride, promethazine hydrochloride, alimemazine tartrate, Examples include dimene donato. Antiallergic substances include tea, green tea, perilla, oligosaccharide, lactic acid bacteria, amlexanox, ibudilast, cromoglycate sodium, tazanolast, tranilast, pemirolast potassium, repirinast, ebastine, azelastine hydrochloride, epinastine hydrochloride, olopatadine hydrochloride, cetirizine hydrochloride, Fexofenadine hydrochloride, levocabastine hydrochloride, oxatomide, ketotifen fumarate, emedastine fumarate, bepotastine pesylate, mequitazine, loratadine, ozagrel hydrochloride, seratrodast, ramatroban, zafirlukast, pranlukast hydrate, montelukast sodium, suplatast tosylate, etc. Can be mentioned. Examples of immunomodulators include arabinoxylan, lactic acid bacteria, β-glucan, ginger, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL- 8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-21, TGF-β, GM-CSF, M-CSF, G-CSF, TNF-α, Examples include TNF-β, LAF, TCGF, BCGF, TRF, BAF, BDG, MP, LIF, OSM, TMF, PDGF, IFN-α, IFN-β, IFN-γ, and the like.

  In addition to the above, the composition of the present invention includes, for example, conjugated linoleic acid, taurine, glutathione, carnitine, creatine, coenzyme Q, glucuronic acid, glucuronolactone, pepper extract, ginger extract, cacao extract, guarana extract, garcinia extract. , Theanine, γ-aminobutyric acid, capsaicin, capsiate, various organic acids, flavonoids, polyphenols, catechins, xanthine derivatives, indigestible oligosaccharides such as fructooligosaccharides, polyvinylpyrrolidone and the like.

  The compounding amount of these additives is appropriately determined according to the form of the composition, the type of additive and the amount of intake to be desired, but is within the range of 0.01 to 70% by mass in the composition of the present invention. Preferably, it exists in the range of 0.1-50 mass%.

  According to the present invention, various antiallergic diseases such as hay fever, allergic conjunctivitis, bronchial asthma, atopic dermatitis and the like can be prevented and / or improved by antihistaminic action. Furthermore, the composition of the present invention has no side effects, has a good flavor and can be easily ingested, and can be easily ingested for a long period of time.

  In addition, by administering the composition of the present invention as a food, feed, cosmetic or pharmaceutical agent in an effective amount as described above, various allergic diseases such as hay fever, allergic conjunctivitis, bronchial asthma, atopy It is possible to provide a method for preventing and / or improving dermatitis.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited only to a following example.

  In the following Examples, the average molecular weight and glutamine content of the wheat protein hydrolyzate were measured by the following methods.

Average molecular weight of wheat protein hydrolyzate:
An aqueous solution of wheat protein hydrolyzate was filtered through a membrane filter having a pore size of 0.45 μm, and the molecular weight was measured by gel filtration. As a column, “Biosil SEC125-5” manufactured by Nippon Bio-Rad Laboratories was used. The measurement conditions were a measurement wavelength of 280 nm, an eluent of 0.2 mM phosphate buffer (pH 6.0, 0.1% SDS), and a flow rate of 0.2 ml / min. In addition, ovalbumin (molecular weight 44 kDa), myoglobulin (molecular weight 17 kDa) and vitamin B12 (molecular weight 1.35 kDa) were used as molecular weight standards.

Glutamine content in wheat protein hydrolyzate:
There are two amino acids containing amide nitrogen, glutamine and asparagine. In wheat protein, 95% by mass or more of amide nitrogen-containing amino acids contained therein is glutamine. That is, even if the amount of amino acid containing amide nitrogen in the hydrolyzate of wheat protein is directly used as the content of glutamine, it does not cause a large error. Therefore, the amount of amide nitrogen-containing amino acid in the hydrolyzate of wheat protein was taken as the glutamine content as it was.

  The content of amide nitrogen contained in the hydrolyzate of wheat protein was determined by the method of quantification of amides in chemical substances by Wilcox [Meth. Enzymol. 11, 36-65 (1967)]. Specifically, a wheat protein hydrolyzate is placed in a Conway flask, 1N hydrochloric acid is added thereto to liberate amide nitrogen in the wheat protein hydrolyzate as ammonia, and the generated ammonia is sanitized. Quantified according to the inspection guidelines [Japan Pharmaceutical Association edited by “Hygiene Test Methods / Comments”, p274-276, Kanehara Publishing (1990)], the amount of amide nitrogen contained in the hydrolyzate of wheat protein is determined from the amount of ammonia quantified, Based on this, the content of the amide nitrogen-containing amino acid was calculated as the glutamine content.

Production Example 1 Production of hydrolyzate of wheat protein (1) 9,700 L of ion-exchanged water, 38 kg of anhydrous citric acid and 1,500 kg of wheat gluten (active gluten, manufactured by Weston Foods Limited) were charged in a reaction kettle and heated to 45 ° C. Later, 2.2 kg of protease (“Protease M Amano” manufactured by Amano Pharmaceutical Co., Ltd.) and 1.1 kg of amylase (“Liquefied Enzyme T” manufactured by Hankyu BioIndustry Co., Ltd.) were added, followed by hydrolysis at 45 ° C. for 5 hours. Subsequently, the pH of the solution was adjusted to 4.4 to 4.5 using a 25% aqueous sodium hydroxide solution, and the enzyme treatment was performed for 5 hours.

(2) Next, after inactivating the protease by maintaining the solution at 80 ° C. for 20 minutes, the solution was cooled to 65 ° C., and 0.5 kg of amylase (“Liquefied enzyme T” manufactured by Hankyu BioIndustry Co., Ltd.) was added thereto. After the starch and fiber contained in the wheat gluten were hydrolyzed, the liquid was kept at 90 ° C. for 20 minutes to inactivate amylase.
(3) Next, after cooling the liquid to 10 ° C. or lower, the solution was heated again to 55 ° C., 100 kg of activated carbon (“Takecol” manufactured by Takeda Pharmaceutical Co., Ltd.) was added thereto, and the mixture was stirred at 55 ° C. for 30 minutes.
(4) The liquid temperature was set to 45 ° C., a concentrated super assistant (“Radiolite” manufactured by Showa Chemical Industry Co., Ltd.) was added, and filtration was performed using a pressure filtration device, and 7,000 L of the filtrate was recovered.

(5) The filtrate collected in (4) above is concentrated under reduced pressure until the Brix value is 20-40, then sterilized by heating at 110 ° C. for 20 seconds using a plate heater, and then cooled to 55 ° C. did.
(6) The liquid obtained in (5) above is spray-dried using a spray drying device under conditions of an air blowing temperature of 160 ° C. and an exhaust air temperature of 80 ° C. About 1,000 kg was obtained in the form.

(7) The wheat protein hydrolyzate powder obtained in (6) above was classified using a 60 mesh sieve (aperture 0.246 mm), and the fine powder that passed through the 60 mesh sieve was recovered.
(8) When the average molecular weight and glutamine content of the wheat protein hydrolyzate recovered in (7) were measured, the average molecular weight was about 8,000 daltons, and the glutamine content was 32% by mass.

Production Examples 2-5. Production of Wheat Protein Hydrolyzate The hydrolysis conditions were appropriately changed in the same manner as in Production Example 1 to obtain a wheat protein hydrolyzate having the properties shown in Table 1 below.

Example 1. Production of tablets 83.8 g of the hydrolyzate of wheat protein obtained in Production Example 1, 10 g of crystalline cellulose (manufactured by Asahi Kasei Co., Ltd.) and 5 g of polyvinylpyrrolidone (manufactured by BASF) were mixed, and 30 ml of ethanol was added thereto. The grains were produced according to a conventional method by a wet method. After drying the obtained granules, 1.2 g of magnesium stearate was added to form granules for tableting, and tableting was performed using a tableting machine to produce 100 tablets each having 1 g ( Wheat protein hydrolyzate content per tablet 0.838 g).

Example 2 Preparation of syrup preparation Boil 400g of purified water, add 750g of white sugar and 100g of the hydrolyzate of the wheat protein obtained in Preparation Example 1 while stirring and dissolve it. In addition, a syrup was prepared with a total amount of 1000 ml (hydrolyzate content of wheat protein per 100 ml of syrup was 10 g).

Example 3 FIG. Manufacture of granules Glutamine peptide GP-1 (average molecular weight 7,000 Dalton, L-glutamine content 32% by mass; manufactured by Nisshin Pharma Co., Ltd.) 600 g, glucose 200 g and acidulant 90 g were mixed, and paste 14 g An aqueous solution in which 1 g of a mixture of sweetener and flavor was dissolved was added, and granules were produced according to a conventional method by a wet method. After drying, the granules were sized to obtain granules (per 4.5 g of a single granule). Wheat protein hydrolyzate content 3 g).

Test Example 1 Test for histamine release from mast cells Mast cells were prepared by culturing cells isolated from bone marrow of Nc / Nga mice in a medium containing IL-3, and sensitized with anti-TNP-IgE antibody. It was. Sensitized cells were suspended in Tyrode solution (0.1% Glucose, 0.1% gelatin, TA, 10 mM HEPES (pH = 7.4) containing 1 mM MgCl ₂ ). While the suspension was dispensed and kept in a 37 ° C. constant temperature bath, the wheat protein hydrolyzate obtained in Production Example 1 was added at a concentration of 2.5, 5, 10, 15 mg / mL, Ten minutes later, 300 μM CaCl ₂ -containing TNP-BSA 300 ng / mL was added, and stimulation with allergen was performed for 20 minutes. The reaction was stopped by adding EDTA, and the amount of free histamine in the supernatant was measured by the liquid chromatograph method under the following conditions.
Measuring instrument: LC-10A (Shimadzu Corporation)
Column: ODP 50-4E (inner diameter 4.6 × 250 mm; Showa Denko)
Column temperature: 37 ° C
Measurement wavelength: ex. 330 nm, em. 430nm
Mobile phase: 50 mM sodium borate (pH 9.5): acetonitrile containing 2 mM OPA, 2 mM N-acetylcysteine = 84: 16
Flow rate: 0.5 mL / min

  In place of the wheat protein hydrolyzate obtained in Production Example 1, histamine release in each concentration of wheat protein hydrolyzate with PBS added as histamine release inhibition rate 0% and histamine amount 0 as 100% The inhibition rate was calculated. The results are shown in Table 2. The antihistamine composition of the present invention suppressed histamine release from mast cells in a concentration-dependent manner. At a concentration of 15 mg / mL, the inhibition rate was about 88%, and histamine release was very strongly suppressed.

Test Example 2 Test for hay fever patients Twenty-seven healthy individuals with subjective symptoms of hay fever were divided into two groups, and one group was ingested with the granule of Example 3 twice daily, in the morning and at night. The remaining group was not ingested (control group). Separately, the amount of pollen in the atmosphere was measured in parallel to monitor the amount of pollen every day. Subjective symptoms were recorded daily in both groups for 5 weeks after judging that the pollen concentration became sufficiently high (50 or more / cm ² ). Recordings were made for sneezing, nasal congestion, stuffy nose, itchy eyes, tearing and sore throat, and scored according to the criteria in Table 3.

  About the score of each test patient, the granule intake group of Example 3 and the control group record the average value of each week for each subjective symptom, and the results of comparison are shown in FIGS. In the group ingesting the composition of the present invention, the score of each subjective symptom was generally lower than that in the non-ingested group, and it was found that the composition of the present invention markedly improved each symptom caused by hay fever. .

Example 4 Manufacture of liquid food To approximately 750 g of pure water at 65 ° C., 40 g of sodium caseinate (manufactured by DMV), 160 g of maltodextrin (manufactured by Sanwa Starch) and 25 g of glutamine peptide GP-1 (manufactured by Nisshin Pharma) are added. Then, 5 g of vitamin mix and a mixture of minerals (trace amount) were added. The mixed solution was put into a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.) and roughly emulsified at about 8000 rpm for 15 minutes. The obtained emulsified liquid was cooled to about 20 ° C., and after adding a fragrance, the final volume was increased. After filling this liquid with 230 g of this liquid in a pouch, the pouch was sealed while purging with nitrogen, and sterilized at 121 ° C. for 15 minutes to obtain a concentrated liquid food. The hydrolyzate content of wheat protein per 230 g of liquid food was about 5 g.

Embodiment 5 FIG. Production of bread 150 g of flour (strong flour) and 2 g of dry yeast were mixed. In addition, 20 g of the wheat protein hydrolyzate obtained in Production Example 2, 20 g of sugar, 3 g of sodium chloride and 6 g of skim milk powder were dissolved in 70 g of hot water, and 1 egg was added and mixed well. After adding this to flour and kneading well by hand, about 40 g of butter was added and kneaded well to make 20 roll bread dough. Next, after fermenting, the egg was coated on the surface and baked in an oven at 180 ° C. for about 15 minutes to produce a roll. This roll contained about 1 g of hydrolyzate of wheat protein per piece.

Example 6 Production of Pasta Meat Sauce A portion of pasta meat sauce (150 g) was placed in a pan, and 5 g of glutamine peptide GP-1 (Nisshin Pharma Co., Ltd.) was added and heated at the same time to prepare a pasta meat sauce. After filling this pouch with a pouch, the pouch was sealed with nitrogen substitution and sterilized at 121 ° C. for 15 minutes to obtain a meat sauce for pasta containing a hydrolyzate of wheat protein.

Example 7 Manufacture of Udon Noodles 15g of glutamine peptide GP-1 (manufactured by Nisshin Pharma Co., Ltd.) and 15g of sodium chloride were dispersed in 150g of water and 300g of wheat flour (medium force flour). Thereafter, the dough was stretched and cut into widths of about 5 mm to produce udon. When this was boiled with boiling water for about 10 minutes, the appearance, taste and texture were good. This udon contained about 5 g of hydrolyzate of wheat protein per serving.

Example 8 FIG. Manufacture of vegetable juice The vegetable protein juice was prepared by adding and mixing the hydrolyzate of the wheat protein obtained in Example 1 to commercially available vegetable juice so that it might become 5 mass%.

Example 9 Production of consomme soup Each slice of onion 100g, carrot 100g, long onion 100g, celery 50g, and tomato 100g is put in a pan, 500g of minced beef meat, 2 egg whites and 1kg of beef bouillon are added. , Boil on low heat for 1 hour while removing aqua and fat floating on the surface, add 50 g of wheat protein hydrolyzate obtained in Example 1 and boil for another 30 minutes, rub with cloth, I got a consomme soup.

Example 10 Ointment production

  B was mixed while heating and dissolving at 70 ° C. to obtain an oil phase. A was mixed while being heated and dissolved at 70 ° C., and the oil phase of B was added thereto for mixing and emulsification. After that, the mixture was cooled and mixed well while adding C to obtain an ointment.

Results of measuring pollen scattering amount in the atmosphere by scoring and recording the subjective symptoms of hay fever (number of sneezing) for the group (intake group) and the non-intake group (control group) administered the composition of the present invention And show together. * Mann-Whitney U test is significantly different from the control group (p <0.05) For the group administered with the composition of the present invention (intake group) and the non-intake group (control group), the result of scoring and recording the subjective symptoms of hay fever (number of nasal congestion) was recorded as the amount of pollen scattering in the atmosphere. It is shown together with the measurement results. * Mann-Whitney U test is significantly different from the control group (p <0.05) Results of measuring pollen scattering amount in the atmosphere with the result of scoring and recording subjective symptoms of hay fever (nasal congestion) for the group administered with the composition of the present invention (intake group) and the non-intake group (control group) And show together. * Mann-Whitney U test is significantly different from the control group (p <0.05) Measurement of pollen scattering in the atmosphere by scoring and recording the subjective symptoms of hay fever (eye itching) for the group (intake group) and the non-intake group (control group) administered the composition of the present invention It shows together with a result. * Mann-Whitney U test is significantly different from the control group (p <0.05) The results of scoring and recording the subjective symptoms of hay fever (the appearance of tears) for the group administered with the composition of the present invention (intake group) and the non-intake group (control group) It is shown together with the measurement results. * Mann-Whitney U test is significantly different from the control group (p <0.05) The results of scoring and recording the subjective symptoms of hay fever (sore throat) for the group administered with the composition of the present invention (intake group) and the non-intake group (control group) And show together. * Mann-Whitney U test is significantly different from the control group (p <0.05)

Claims (5)

  An antihistamine composition containing a hydrolyzate of wheat protein.   A composition for preventing and / or ameliorating an allergic disease comprising the antihistamine composition according to claim 1.   The composition according to claim 2, wherein the allergic disease is hay fever.   The composition according to any one of claims 1 to 3, comprising a wheat gluten hydrolyzate as a wheat protein hydrolyzate.   The composition according to any one of claims 1 to 4, comprising a peptide having an L-glutamine content of 15 to 60% by mass and an average molecular weight of 200 to 100,000 daltons as a hydrolyzate of wheat protein.

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