JP5408882B2 - Salivary secretion promoter - Google Patents

Description

  The present invention relates to a salivary secretion promoter and the like that heals dryness in the oral cavity.

  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.

  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.

  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.

  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.

  Therefore, promoting saliva secretion and moisturizing the oral cavity is important for keeping the oral cavity refreshing and preventing oral diseases.

  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.

  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.

  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.

  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.

  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.

  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.

Japanese Patent Laid-Open No. 8-175934

  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.

  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) A salivary secretion promoter characterized by containing at least one nucleotide selected from the group consisting of adenylic acid, guanylic acid, cytidylic acid and uridylic acid.

  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.

  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.

  The nucleotide used in the present invention may be any nucleotide that can be used in foods and oral products, for example, one or more selected from the group consisting of adenylic acid, cytidylic acid, uridylic acid or guanylic acid. Can be used. However, inosinic acid is excluded from nucleotides to be used because it has a very low salivary secretion promoting effect.

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.

  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.

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.

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.

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.

  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.

  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.

  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.

  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.

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.

  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.

  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.

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

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) 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.

(candy)
Xylitol 88.5%, Sorbitol 10%, Fragrance 0.3%, Sucralose 0.1%, Colorant 0.1%, Disodium guanylate 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 (1)

A saliva secretion promoter for blending in an oral composition, comprising at least one nucleotide selected from the group consisting of adenylic acid, cytidylic acid and uridylic acid.