JP2013224322A - Salivator - Google Patents

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JP2013224322A
JP2013224322A JP2013139430A JP2013139430A JP2013224322A JP 2013224322 A JP2013224322 A JP 2013224322A JP 2013139430 A JP2013139430 A JP 2013139430A JP 2013139430 A JP2013139430 A JP 2013139430A JP 2013224322 A JP2013224322 A JP 2013224322A
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acid
salivary secretion
salivator
oral
nucleotide
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Kazuki Endo
和樹 遠藤
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Yamasa Shoyu KK
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Yamasa Shoyu KK
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Abstract

PROBLEM TO BE SOLVED: To provide a salivator and the like that stimulate saliva secretion without spoiling sense of taste even when applied orally, and has excellent safety.SOLUTION: A salivator includes at least one type of nucleotide selected from the group consisting of adenylic acid, uridylic acid, and cytidylic acid. The salivator has very few problems regarding sense of taste, and therefore can be included in oral compositions and food compositions without restrictions. In addition, the salivator as also known as a biological material and a food additive. The salivator is highly safe and ideal as a material for oral products and food products.

Description

本発明は、口腔内の乾燥を癒す唾液分泌促進剤等に関する。   The present invention relates to a salivary secretion promoter and the like that heals dryness in the oral cavity.

唾液腺は、咀嚼、消化、味覚および正常な粘膜の維持に必要な唾液分泌、並びにホルモンや成長因子の産生等の機能を有し、体の恒常性の維持に重要な役割を担っている。   The salivary glands have functions such as salivation necessary for mastication, digestion, taste and maintenance of normal mucous membranes, and production of hormones and growth factors, and play an important role in maintaining body homeostasis.

唾液分泌が低下する原因には、主としてシェーグレン症候群、糖尿病、肝硬変、腎疾患等の内科疾患、加齢による分泌機能低下、エイズ、唾液腺の器質的変化を起こす各種疾患、癌治療における放射線照射および各種薬物による副作用等が挙げられる。   Causes of decreased salivary secretion are mainly internal diseases such as Sjogren's syndrome, diabetes, liver cirrhosis, and kidney disease, decreased secretory function due to aging, various diseases that cause organic changes in salivary glands, radiation in cancer treatment and various Examples include side effects caused by drugs.

唾液分泌が低下することによって生ずる口腔内乾燥症により、口臭発生、口腔内不快感および感染症または炎症の発生等の症状が現れる。特に、唾液腺の機能が低下した老人に、副作用として唾液分泌抑制作用を有する薬物を投与する際には注意が必要である。   Symptoms such as the generation of bad breath, oral discomfort and the occurrence of infections or inflammation appear due to xerostomia caused by a decrease in saliva secretion. In particular, care should be taken when administering a drug having a salivary secretion-inhibiting action as a side effect to an elderly person whose salivary gland function has declined.

また、口腔内の乾燥は日常生活でも経験され、べとべとした不快感、会話の困難さ、口臭の発生等を伴う。さらに病的になると、口腔内菌叢の変化から、う蝕、歯周疾患、粘膜の感染症等、口腔機能の不全(咀嚼障害、嚥下困難、味覚異常等)を生ずる。   In addition, drying in the oral cavity is also experienced in daily life, and is accompanied by sticky discomfort, difficulty in conversation, and the generation of bad breath. Furthermore, when pathological, the oral microbiota changes, resulting in oral function defects (mastication disorder, difficulty swallowing, abnormal taste, etc.) such as caries, periodontal disease, mucosal infection, and the like.

従って、唾液の分泌を促進して口腔内を潤すことは、口腔を爽快に保ち、口腔疾患を予防する上で重要である。   Therefore, promoting saliva secretion and moisturizing the oral cavity is important for keeping the oral cavity refreshing and preventing oral diseases.

そこで、口腔内を爽快に保ち、口腔内を潤すことで口腔疾患を予防するために、例えば、保湿剤であるヒアルロン酸の利用が提案されている。しかし、ヒアルロン酸には保湿作用はあるものの、積極的に唾液分泌を促進する作用は認められない。   In order to prevent oral diseases by keeping the oral cavity refreshing and moisturizing the oral cavity, for example, the use of hyaluronic acid as a moisturizing agent has been proposed. However, although hyaluronic acid has a moisturizing action, it does not positively promote salivary secretion.

一方、積極的に唾液の分泌を促進して口腔内を潤すことも提案され、その手段として味覚的、ないしは嗅覚的に刺激を与える方法が知られており、例えば有機酸を唾液分泌促進剤として使用する方法や、グレープフルーツ調香料等を用いる方法が提案されている。   On the other hand, it has also been proposed to actively promote the secretion of saliva to moisturize the oral cavity, and as a means there is known a method of giving a taste or olfactory stimulus, for example, using an organic acid as a saliva secretion promoter The method of using and the method of using a grapefruit flavoring etc. are proposed.

しかしながら、酸味等の味覚刺激や嗅覚刺激成分による唾液分泌促進効果は、刺激を受けた直後の短時間に集中していることから、味覚刺激、嗅覚刺激の消失とともに効果が消失し、効果の持続性に欠けるという問題点を有していた。また、とくに味覚刺激を用いた方法では、有機酸により歯を傷める危険性から使用について制約が生じ、さらには促進剤自身が強い味や匂いを呈することから食品・口腔内用品としての用途が制限されていた。   However, the salivary secretion-promoting effect by taste stimuli such as sourness and olfactory stimuli concentrates in a short period of time immediately after being stimulated, so the effect disappears with the disappearance of taste and olfactory stimuli, and the effect continues It had the problem of lacking in nature. In particular, in the method using taste stimuli, there are restrictions on the use due to the risk of damaging teeth by organic acids, and further, the accelerator itself has a strong taste and smell, limiting the use as food and oral products It had been.

他にも、有機酸及び羅漢果またはその抽出物を含有する唾液分泌促進剤や、コーラノキ種子末またはその抽出成分及び有機酸を含有する唾液分泌促進剤が提案されているが、これらの唾液分泌促進剤についても有機酸を併用することが必須または推奨されており、上記と同様の問題が生じうる。   In addition, salivary secretion promoters containing organic acids and Rakan fruit or extracts thereof, and saliva secretion promoters containing cola seed powder or its extract components and organic acids have been proposed. It is essential or recommended to use an organic acid in combination with the agent, and the same problem as described above may occur.

さらに、ムスカリン受容体を標的とした薬物や、PAR−2を標的とした薬物等の唾液分泌促進物質が報告されているが、これらの薬物には副作用の懸念がある。   In addition, salivary secretion-promoting substances such as drugs targeting muscarinic receptors and drugs targeting PAR-2 have been reported, but these drugs have a side effect.

一方、ヌクレオチドは食品や口腔用品に広く含まれ、あるいは添加されている物質であり、安全に利用できることが知られている。また、例えば特許文献1に示されるように、イノシン酸などのヌクレオチドの使用量を限定すれば、味覚に強い影響を及ぼすものではないことも公知である。しかしながら、従来、ヌクレオチドを唾液分泌促進のために使用した例は知られていない。   On the other hand, nucleotides are substances that are widely contained or added to foods and oral products and are known to be safe to use. It is also known that, for example, as disclosed in Patent Document 1, if the amount of nucleotides such as inosinic acid is limited, it does not strongly affect the taste. However, there has been no known example in which nucleotides are used for promoting salivary secretion.

特開平8−175943号公報Japanese Patent Laid-Open No. 8-175934

本発明は、従来の唾液分泌促進方法の問題点を解決するために、口腔内に適用しても味覚を損なうことなく唾液分泌を促し、しかも安全性に優れた唾液分泌促進剤等を提供することを目的とする。   In order to solve the problems of the conventional saliva secretion promoting method, the present invention provides a saliva secretion promoting agent that promotes saliva secretion without impairing the taste even when applied to the oral cavity and that is excellent in safety. For the purpose.

本発明者は、上記目的を達成するため鋭意検討を行った結果、イノシン酸を除くヌクレオチドに優れた唾液分泌促進活性があることを知見し、これを発展させ、本発明をなすに至ったものである。すなわち、本発明は以下の発明を包含する。   As a result of intensive studies to achieve the above object, the present inventor has found that nucleotides other than inosinic acid have an excellent salivary secretion promoting activity, and have developed this to achieve the present invention. It is. That is, the present invention includes the following inventions.

(1)アデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有し、かつ他の呈味成分を含有しない唾液分泌促進剤。
(2)アデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有し、かつイノシン酸および他の呈味成分を含有しない唾液分泌促進剤。
(3)ヌクレオチドがアデニル酸である、(1)または(2)に記載の唾液分泌促進剤。
(4)ヌクレオチドがウリジル酸である、(1)または(2)に記載の唾液分泌促進剤。
(5)ヌクレオチドがシチジル酸である、(1)または(2)に記載の唾液分泌促進剤。
(1) A salivary secretion promoter containing at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid, and cytidylic acid, and containing no other taste components.
(2) A salivary secretion promoter containing at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid and cytidylic acid, and containing no inosinic acid and other taste components.
(3) The salivary secretion promoter according to (1) or (2), wherein the nucleotide is adenylic acid.
(4) The salivary secretion promoter according to (1) or (2), wherein the nucleotide is uridylic acid.
(5) The salivary secretion promoter according to (1) or (2), wherein the nucleotide is cytidylic acid.

(6)有効成分としてアデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有せしめることを特徴とする、唾液分泌促進剤の製造法。
(7)ヒトを除く動物の唾液分泌を促進するために、アデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有する唾液分泌促進剤を使用する方法。
(6) A method for producing a salivary secretion promoter, comprising at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid and cytidylic acid as an active ingredient.
(7) A method of using a salivary secretion promoter containing at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid and cytidylic acid in order to promote salivation of animals other than humans.

本発明における唾液分泌促進剤は、味覚に対する問題がほとんど無いため、口腔用組成物、食品組成物に制限なく配合できる。また、本発明の唾液分泌促進剤は生体内物質や食品添加物としても知られており、安全性が高く、口腔用品、食品の素材として最適である。   Since the salivary secretion promoter in the present invention has almost no problem with taste, it can be incorporated into oral compositions and food compositions without limitation. Moreover, the salivary secretion promoter of the present invention is also known as an in vivo substance or food additive, has high safety, and is optimal as a material for oral products and foods.

さらに、本発明の方法あるいは唾液分泌促進剤または飲食品を用いれば、重度な口腔乾燥症に対しても口腔粘膜に潤いを与えることができ、結果として口腔内の乾燥に伴うべとべとした不快感、会話の困難さ、口臭の発生等が速やかに解消される。したがって、う蝕、歯周疾患、粘膜の感染症等、口腔機能の不全をも予防することができることが期待できる。   Furthermore, if the method of the present invention or the salivary secretion promoter or food or drink is used, it can moisturize the oral mucosa even for severe xerostomia, resulting in sticky discomfort associated with dry mouth, The difficulty of conversation and the occurrence of bad breath are quickly resolved. Therefore, it is expected that oral function defects such as caries, periodontal disease, mucosal infection, etc. can be prevented.

本発明で使用するヌクレオチドとしては、食品・口腔用品等に利用可能なものを用いればよく、例えばアデニル酸およびシチジル酸からなる群から選択された1種または2種以上を使用することができる。ただし、イノシン酸は、唾液分泌促進効果が極めて低いため、使用するヌクレオチドからは除外される。   The nucleotide used in the present invention may be any nucleotide that can be used in foods, oral products and the like. For example, one or more selected from the group consisting of adenylic acid and cytidylic acid can be used. However, inosinic acid is excluded from nucleotides to be used because it has a very low salivary secretion promoting effect.

また、ヌクレオチドを複数混合したものとしては、単品同士を混合したもののほか、RNAを酵素分解して得られるヌクレオチド混合物、あるいはその混合物をさらに分画、塩析、沈殿等の簡単な精製処理を施したものも本発明のヌクレオチドとして使用することができる。   In addition to a mixture of single nucleotides, a mixture of single nucleotides, a nucleotide mixture obtained by enzymatic degradation of RNA, or a mixture thereof is further subjected to simple purification treatments such as fractionation, salting out, and precipitation. These can also be used as the nucleotides of the present invention.

これらのヌクレオチドは、遊離の形態だけでなく、塩の形態であってもよく、ナトリウム塩、カリウム塩などのアルカリ金属塩、カルシウム塩などのアルカリ土類金属塩等も本発明のヌクレオチドとして利用し得る。   These nucleotides may be in the form of salts as well as free forms. Alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and the like are also used as the nucleotides of the present invention. obtain.

本発明の唾液分泌促進剤(ヌクレオチド)を、口腔用組成物、食品組成物に使用する場合、全体に対するヌクレオチドの配合量は、好ましくは0.05〜10%(質量%(w/v)、以下同様)、とくに好ましくは 0.1〜5%とすることができる。配合量が少なすぎると良好な効果が発揮されないおそれがあり、また配合量が10%を超えるとヌクレオチドそのものの呈味が強くなり過ぎる場合がある。 When the salivary secretion promoter (nucleotide) of the present invention is used in an oral composition or food composition, the amount of nucleotides based on the total is preferably 0.05 to 10% (mass% (w / v), The same shall apply hereinafter), particularly preferably 0.1 to 5%. If the blending amount is too small, good effects may not be exhibited, and if the blending amount exceeds 10%, the taste of the nucleotide itself may be too strong.

この場合、本発明の唾液分泌促進剤の投与量は唾液分泌促進有効量であり、適宜選定されるが、一回の投与量は0.005〜1g/成人1名(体重60kg)の範囲であることが好ましい。 In this case, the dosage of the salivary secretion-promoting agent of the present invention is a salivary secretion-promoting effective amount, and is selected as appropriate. The single dose is in the range of 0.005 to 1 g / one adult (weight 60 kg). Preferably there is.

本発明の唾液分泌促進剤は、口腔用組成物(歯磨類、洗口剤、咀嚼錠、口腔用軟膏、うがい用錠剤、トローチ、人工唾液、義歯安定剤、給水吸引機能付き口腔ケアシステム用溶液等)、食品組成物(嚥下補助剤、キャンディ、チューインガム、ドリンク剤、グミ等)に配合でき、その種類、剤型に応じ、上記必須成分に加えて任意成分としてその他の公知の添加剤を配合することができる。 The salivary secretion promoter of the present invention is a composition for oral cavity (a dentifrice, mouthwash, chewing tablet, oral ointment, gargle tablet, troche, artificial saliva, denture stabilizer, solution for oral care system with water supply suction function) Etc.), food compositions (swallowing aids, candy, chewing gum, drinks, gummi, etc.) and other known additives as optional ingredients in addition to the above essential ingredients depending on the type and dosage form can do.

例えば、洗口液等の液状口腔用組成物及びペースト状口腔用組成物の場合、本発明の唾液分泌促進剤の他に、粘稠剤、粘結剤、界面活性剤、甘味剤、防腐剤、着色剤、香料、各種有効成分等を配合し得る。これら成分を水と混合して製造することができる。また、歯磨組成物の場合であれば研磨剤を、液状組成物である場合にはエタノール等の非毒性溶剤を配合することができる。   For example, in the case of a liquid oral composition such as a mouthwash and a paste-like oral composition, in addition to the saliva secretion promoter of the present invention, a thickener, a binder, a surfactant, a sweetener, a preservative , Coloring agents, fragrances, various active ingredients and the like can be blended. These components can be produced by mixing with water. In the case of a dentifrice composition, an abrasive can be blended, and in the case of a liquid composition, a non-toxic solvent such as ethanol can be blended.

さらに、口腔用組成物を、錠剤、トローチ剤等の固形製剤として調製する場合は、非毒性の賦形剤、結合剤、崩壊剤、滑沢剤、さらに上述した界面活性剤、甘味剤、香料等を配合し得る。   Further, when the oral composition is prepared as a solid preparation such as a tablet or troche, non-toxic excipients, binders, disintegrants, lubricants, and the above-mentioned surfactants, sweeteners, and fragrances. Etc. may be blended.

一方、食品組成物においても、その食品の種類に応じた食品素材が用いられる。例えば、チューインガムの場合であれば、砂糖等の糖類、ガムベース等を含有するものとし得、キャンディ等の飴菓子の場合であれば、水飴、砂糖等を含有するものとし得る。   On the other hand, also in the food composition, a food material corresponding to the type of the food is used. For example, in the case of chewing gum, it may contain sugars such as sugar, gum base and the like, and in the case of candy sweets such as candy, it may contain chickenpox, sugar and the like.

以下、実施例を示し、本発明を具体的に説明するが、本発明がこれに限定されないことは明らかである。   Hereinafter, the present invention will be described in detail with reference to examples, but it is clear that the present invention is not limited thereto.

実施例1:ヌクレオチドによる唾液分泌促進効果
唾液分泌量の測定は既知の方法(Jpn.J.Pharmacol.78,373−380,1998)に準じて行った。ICR系雄性マウス(各群10匹、39〜42週齢、体重43〜57g)をペントバルビタールナトリウムで麻酔し(20mg/kg,ip+60mg/kg,s.c.)、投与する物質の種類に応じて5つの群に分けた。
Example 1: Salivary secretion promoting effect by nucleotide Salivary secretion was measured according to a known method (Jpn. J. Pharmacol. 78, 373-380, 1998). ICR male mice (10 mice in each group, 39-42 weeks old, body weight 43-57 g) are anesthetized with sodium pentobarbital (20 mg / kg, ip + 60 mg / kg, sc), depending on the type of substance administered Divided into 5 groups.

マウスの口腔内にあらかじめ重量を調整(25mg±10%)・測定しておいたボール状の脱脂綿を挿入し、直ちに、4つの群に対してそれぞれアデニル酸、グアニル酸二ナトリウム、シチジル酸、ウリジル酸二ナトリウムの10%水溶液を100μl滴下した。対照群には蒸留水100μlを滴下した。   The ball-shaped absorbent cotton whose weight was adjusted (25mg ± 10%) and measured in advance in the mouse's mouth was inserted, and immediately adenylic acid, disodium guanylate, cytidylic acid, uridyl for each of the four groups 100 μl of a 10% aqueous solution of disodium acid was added dropwise. 100 μl of distilled water was added dropwise to the control group.

10分後に脱脂綿を回収し、直ちに新たなボール状脱脂綿(25mg±10%)を挿入した。20分後、その脱脂綿を回収し、直ちに重量を測定し、挿入前と挿入後の重量差を唾液分泌量とした。   Absorbent cotton was collected after 10 minutes, and new ball-shaped absorbent cotton (25 mg ± 10%) was immediately inserted. After 20 minutes, the absorbent cotton was collected and immediately weighed, and the difference in weight before and after insertion was defined as the saliva secretion amount.

測定の結果、表1に示す4種のヌクレオチドは著しい唾液分泌増加作用を示すことが確認された。尚、表中のデータは以下の式にて各種ヌクレオチドの投与による唾液分泌増加率を算出後、増加率を%で表したものである。
増加率(%)=(各種ヌクレオチド投与群の唾液分泌量/対照群の唾液分泌量)×100−100
As a result of the measurement, it was confirmed that the four types of nucleotides shown in Table 1 showed a remarkable salivary secretion increasing action. The data in the table represents the increase rate in% after calculating the increase rate of saliva secretion by administration of various nucleotides by the following formula.
Increase rate (%) = (saliva secretion amount of various nucleotide administration groups / saliva secretion amount of control group) × 100-100

Figure 2013224322
Figure 2013224322

実施例2:各種組成物例
(1)唾液分泌促進剤を含む口腔用品
以下の組成に従って、本発明に記載の唾液分泌促進剤を含む洗口剤を作製した。
水分80.49%、エタノール8%、グリセリン8%、ツウィーン−20 1.5%、クエン酸1%、パラベン0.01%、アデニル酸1%
Example 2: Various composition examples (1) Oral products containing a saliva secretion promoter A mouthwash containing the saliva secretion promoter described in the present invention was prepared according to the following composition.
Water 80.49%, ethanol 8%, glycerin 8%, Tween-20 1.5%, citric acid 1%, paraben 0.01%, adenylic acid 1%

(2)唾液分泌促進剤を含む食品
以下の組成に従って、本発明に記載の唾液分泌促進剤を含むキャンディ及びチューインガムを作製した。
(2) Food containing saliva secretion promoter A candy and chewing gum containing the saliva secretion promoter according to the present invention were prepared according to the following composition.

(キャンディ)
キシリトール88.5%、ソルビトール10%、香料0.3%、スクラロース0.1%、着色剤0.1%、グアニル酸二ナトリウム1%
(candy)
Xylitol 88.5%, Sorbitol 10%, Fragrance 0.3%, Sucralose 0.1%, Colorant 0.1%, Disodium guanylate 1%

(チューインガム)
ガムベース25%、キシリトール40%、パラチニット30%、マルチトールシロップ2.5%、軟化剤0.9%、アスパルテーム0.1%、香料0.5%、ウリジル酸二ナトリウム1%
(Chewing gum)
25% gum base, 40% xylitol, 30% palatinit, 2.5% maltitol syrup, 0.9% softener, 0.1% aspartame, 0.5% fragrance, 1% disodium uridylate

Claims (7)

アデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有し、かつ他の呈味成分を含有しない唾液分泌促進剤。 A salivary secretion promoter containing at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid and cytidylic acid, and containing no other taste components. アデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有し、かつイノシン酸および他の呈味成分を含有しない唾液分泌促進剤。 A salivary secretion promoter containing at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid and cytidylic acid, and containing no inosinic acid and other taste components. ヌクレオチドがアデニル酸である、請求項1または2に記載の唾液分泌促進剤。 The salivary secretion promoter according to claim 1 or 2, wherein the nucleotide is adenylic acid. ヌクレオチドがウリジル酸である、請求項1または2に記載の唾液分泌促進剤。 The salivary secretion promoter according to claim 1 or 2, wherein the nucleotide is uridylic acid. ヌクレオチドがシチジル酸である、請求項1または2に記載の唾液分泌促進剤。 The salivary secretion promoter according to claim 1 or 2, wherein the nucleotide is cytidylic acid. 有効成分としてアデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有せしめることを特徴とする、唾液分泌促進剤の製造法。 A method for producing a salivary secretion promoter, characterized by containing at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid and cytidylic acid as an active ingredient. ヒトを除く動物の唾液分泌を促進するために、アデニル酸、ウリジル酸およびシチジル酸からなる群から選ばれた少なくとも1種のヌクレオチドを含有する唾液分泌促進剤を使用する方法。 A method of using a salivary secretion enhancer containing at least one nucleotide selected from the group consisting of adenylic acid, uridylic acid and cytidylic acid, in order to promote salivation of animals other than humans.
JP2013139430A 2013-07-03 2013-07-03 Salivator Pending JP2013224322A (en)

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JP2001314172A (en) * 1999-09-20 2001-11-13 Meiji Milk Prod Co Ltd Immunoactivating composition
JP2002173425A (en) * 2000-12-07 2002-06-21 Kao Corp Throat care agent
JP2005052041A (en) * 2003-08-01 2005-03-03 Hosoda Shc:Kk Seasoning composition
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WO2007023800A1 (en) * 2005-08-22 2007-03-01 Yasuyuki Yamada Foods

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Publication number Priority date Publication date Assignee Title
JP2001314172A (en) * 1999-09-20 2001-11-13 Meiji Milk Prod Co Ltd Immunoactivating composition
JP2002173425A (en) * 2000-12-07 2002-06-21 Kao Corp Throat care agent
JP2005052041A (en) * 2003-08-01 2005-03-03 Hosoda Shc:Kk Seasoning composition
WO2006030980A1 (en) * 2004-09-17 2006-03-23 Ajinomoto Co., Inc. Agent and food for preventing/improving functional digestive disorder
JP2006131618A (en) * 2004-10-04 2006-05-25 Taisho Pharmaceut Co Ltd Zinc compound-formulated composition
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