JP2016175901A - Composition for oral care comprising l-aspartic acid or salt thereof, and nicotinamide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for oral care that wets and smoothen an oral cavity and has excellent saliva secretion promoting action.SOLUTION: A composition for oral care comprises L-aspartic acid or salt thereof, and nicotinamide.SELECTED DRAWING: None

Description

  The present invention relates to an oral care composition having an excellent salivary secretion promoting action that moisturizes and smoothes the oral cavity.

  Saliva is secreted from the three major salivary glands (the parotid gland, the submandibular gland, the sublingual gland) in the oral cavity and several small salivary glands, and the daily secretion amount is 1 to 1.5 L on average. Saliva functions include oral self-cleaning, oral moistening, taste media, digestive action, antibacterial action, excretion, and buffering, and various functions essential for maintaining health have.

  However, salivary secretion is known to decrease due to salivary gland disorders, side effects of various drugs, mouth breathing, aging, daily life stress, and the like. Many cases have been introduced in which daily life becomes difficult, such as difficulty in speaking, difficulty in eating, and tendency to become tooth decay when saliva secretion decreases.

  When saliva secretion decreases, xerostomia (dry mouth) is caused, and various unpleasant symptoms such as tongue pain, throat discomfort, dysphagia, taste disorder, etc. appear not only in the dry mouth, QOL in daily life is significantly reduced. In addition, if the dry mouse condition lasts for a long time, it cannot be ignored the effects on oral problems such as caries, periodontal disease, bad breath, and systemic symptoms such as infections.

  Conventionally, various drugs such as nicotinamide are sometimes used for treatment of dry mice (Non-patent Document 1).

  In addition, drugs such as cevimeline hydrochloride and pilocarpine hydrochloride may be used as an improving agent for dry mice derived from Sjogren's syndrome (Non-patent Document 2).

  Since dry mice are due to a decrease in the amount of saliva secreted from the salivary glands in the oral cavity, a drug that promotes saliva secretion by acting locally is desired rather than a drug that has a systemic effect. Attempts have been made to improve the salivary secretion effect by administering the above-mentioned drug into the oral cavity as an oral rinse preparation, but the current state of the art has not yet reached a general therapeutic method (Non-Patent Documents 3 and 4). .

Swedish dental journal 14: 153-161 (1990) Dry Mouth Clinical, 2007, 128-135, Bio-Dental Publishing Pharmaceutical Journal, 40 (5), 175-179, 2004 Japanese Journal of Oral Surgery, 55, 273 pages, 2009

  An object of the present invention is to provide an oral care composition having an excellent salivary secretion promoting action.

  As a result of intensive studies to solve such problems, the present inventors have shown that L-aspartic acid or a salt thereof and nicotinamide have an excellent salivary secretion promoting action, and can moisturize and smooth the oral cavity. We have found that this is possible and have completed the present invention. That is, the present invention is an oral care composition containing L-aspartic acid or a salt thereof and nicotinamide.

That is, the present invention relates to the following (1) to (3).
(1) An oral care composition containing L-aspartic acid or a salt thereof and nicotinamide.
(2) The composition according to (1), wherein the L-aspartic acid or a salt thereof is sodium L-aspartate.
(3) The composition according to (1) or (2), wherein the oral care is oral moistening and / or oral cleaning.

As another aspect, the present invention relates to the following (4) to (7).
(4) A composition for oral care containing L-aspartic acid or a salt thereof and nicotinamide.
(5) The composition according to (4), further comprising L-menthol.
(6) The composition according to (4) or (5), wherein L-aspartic acid or a salt thereof is sodium L-aspartate.
(7) The composition according to any one of (4) to (6), wherein the oral care is oral moistening and / or oral cleaning.

  ADVANTAGE OF THE INVENTION According to this invention, the composition for oral care which has the outstanding salivary secretion promotion effect can be provided. By using the composition of the present invention for oral care, the oral cavity can be moisturized and smoothed, and is effective, for example, in preventing and improving dry mouth.

The results of total salivary secretion for 30 minutes after administration of nicotinamide alone, L-aspartate alone, nicotinamide and sodium L-aspartate administration solution, and control administration solution (n = 4) are shown. Results of total saliva secretion for 30 minutes after administration of nicotinamide and sodium L-aspartate, nicotinamide, sodium L-aspartate and L-menthol, and control solution (n = 4) Represents.

  The “L-aspartic acid or a salt thereof” used in the present invention refers to L-aspartic acid or a salt based on the carboxy group of L-aspartic acid. Examples of the salt based on the carboxy group of L-aspartate include sodium L-aspartate, calcium L-aspartate, potassium L-aspartate, and the like.

  The term “nicotinamide” used in the present invention refers to an amide of nicotinic acid.

  The “L-menthol” used in the present invention may be used as a single agent of L-menthol or a fragrance containing L-menthol.

  In the present invention, “oral care” refers to maintaining the function of the oral cavity, and aims to improve QOL by preventing oral diseases and promoting health maintenance. For example, oral cavity moistening or oral cavity cleaning with saliva is exemplified.

  The present invention is used as pharmaceuticals, quasi drugs, cosmetics and the like.

  The form of this invention and the application method to an oral cavity are not specifically limited. For example, mouthwash, toothpaste, liquid toothpaste, toothpaste, gum, troche, buccal tablets, gingival adhesive tape, oral gel, oral ointment, oral spray , Oral paste, oral paste, oral pill, oral tablet, oral powder, oral powder, oral liquid, oral suspension, oral emulsion, oral cavity Examples include granules for internal use and capsules for oral cavity. Mouthwash (mouth wash), toothpaste, liquid toothpaste or toothpaste are preferred.

  In the present invention, the amount of nicotinamide in the composition is preferably 0.01 to 16% by weight, more preferably 0.1 to 8% by weight. In the present invention, the concentration of L-aspartic acid or a salt thereof in the composition is preferably 0.01 to 16% by weight, more preferably 0.1 to 8% by weight.

  The compounding quantity in the composition of L-menthol in this invention becomes like this. Preferably it is 0.001-1 weight%, More preferably, it is 0.01-0.5 weight%.

  In the present invention, L-aspartic acid or a salt thereof and nicotinamide can be mixed and used in an arbitrary ratio.

  In the present invention, L-aspartic acid or a salt thereof, nicotinamide, and L-menthol can be mixed and used at an arbitrary ratio.

  In the present invention, wetting agents, pH adjusting agents, flavoring agents, preservatives, fragrances, solubilizers and the like can be added as appropriate.

  The wetting agent is not particularly limited as long as it is commercially available as a raw material for pharmaceuticals, foods and cosmetics. For example, polyhydric alcohol, more specifically sorbit, glycerin, concentrated glycerin, ethylene glycol, propylene glycol, 1,3-butylene. Glycol, propanediol (1,3-propanediol), polyethylene glycol, polypropylene glycol, xylite, malt, lactit, trehalose, sodium hyaluronate, hydrolyzed collagen, etc., and one or a combination of two or more of these It can select suitably and can mix | blend as needed.

  The pH of the composition for oral care of the present invention is preferably in the range of 4.5 to 8.0. Examples of the pH adjuster that can be used in the present invention include phosphoric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, citric acid, malic acid, pyrophosphoric acid, tartaric acid. , Acetic acid or a salt thereof, sodium hydroxide and the like. These 1 type, or 2 or more types of combination can be selected suitably, and can be mix | blended as needed.

  Examples of the corrigent include, for example, saccharin, sodium saccharin, disodium glycyrrhizinate, trisodium glycyrrhizinate, sucrose, glucose, fructose, lactose, honey, aspartame, stevia, sucralose, xylitol, inositol, D-sorbitol, D-mannitol, Raffinose, lactulose, lactitol, erythritol, reduced palatinose, palatinose, palatinit, acesulfame K, maltose, maltosyl trehalose or maltitol. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.

  Examples of the preservative include parabens (paraoxybenzoic acid esters) such as methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben and benzylparaben, alcohols such as phenoxyethanol and ethanol, or sorbic acid and benzoic acid. Examples thereof include acids, dehydroacetic acid, propionic acid, and salts thereof. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.

  Examples of the fragrance include L-menthol, peppermint, spearmint or fruit fragrance, mint oil and the like. The perfume also has the advantage of stimulating salivation. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.

  You may add a solubilizer in order to accelerate | stimulate melt | dissolution of the said additive and medicinal component in the water which is the main base of this invention. Examples of such a solubilizer include polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, and polyethylene glycol. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.

  In addition, in the case of dentifrice and ointment, an abrasive, a foaming agent, and a thickener are appropriately used.

  The present invention can further contain medicinal components such as antibacterial agents, anti-inflammatory agents, fluorides, vitamins, and herbal extracts. These medicinal ingredients are not particularly limited as long as they can be used for pharmaceuticals and the like.

  Examples Examples and preparations are shown below, and the present invention will be described in more detail. However, the scope of the present invention is not limited to these examples.

Example 1 Salivary secretion promoting action test 1
(1) Test substance Nicotinamide was manufactured by Tokyo Chemical Industry Co., Ltd., and L-aspartate sodium was manufactured by Peptide Institute.

(2) Animals used Slc: Wistar male rats [Japan SLC Co., Ltd.] 6 weeks old were purchased and quarantined and acclimatized.

(3) Test method Rats that have completed the quarantine / acclimation period (6 days) are anesthetized with urethane and α-chloralose administered intraperitoneally, and a tracheal cannula is placed to secure the airway. To prevent, the esophagus was ligated with sutures.
Next, nicotinamide, sodium L-aspartate, or a 1: 1 mixture of nicotinamide and sodium L-aspartate was prepared to 160 mg / mL using a medium (4% sodium carboxymethylcellulose aqueous solution: CMC aqueous solution). 100 μL of the test substance administration solution was administered into the oral cavity with a micropipette. As a control, 100 μL of the medium (4% CMC aqueous solution) was administered into the oral cavity.
Ten minutes after administration of the medium or test substance, the medium or administration liquid in the oral cavity was wiped with a cotton ball having a tare weight measured. The saliva secretion amount during administration was estimated by subtracting the weight of the tare and medium or test substance administration liquid from the weight after wiping.
Immediately after wiping off the intraoral medium or administration solution, a tare weight-measured cotton ball was placed in the oral cavity. In any group, the cotton balls were changed every 10 minutes, and the saliva secretion amount was measured by subtracting the weight after the replacement. The measurement was carried out until 30 minutes later.

(4) Test results Table 1 and Fig. 1 show the measurement results of total salivary secretion for 30 minutes after administration of each test substance and control (vehicle) (both n = 4).
From the figure and table, an unexpected result that an excellent salivary secretion promoting action was expressed by using nicotinamide and sodium L-aspartate together was obtained.

(Example 2) Salivary secretion promoting action test 2
(1) Test substance Nicotinamide was manufactured by Tokyo Chemical Industry Co., Ltd., L-sodium aspartate was manufactured by Peptide Institute, and L-menthol was manufactured by Suzuki Hikaru.

(2) Animals used Slc: Wistar male rats [Japan SLC Co., Ltd.] 6 weeks old were purchased and quarantined and acclimatized.

(3) Test method Rats that have completed the quarantine / acclimation period (6 days) are anesthetized with urethane and α-chloralose administered intraperitoneally, and a tracheal cannula is placed to secure the airway. To prevent, the esophagus was ligated with sutures. Next, using a medium (4% CMC aqueous solution), a mixture of nicotinamide 75 mg / mL and sodium L-aspartate 75 mg / mL, nicotinamide 75 mg / mL, sodium L-aspartate 75 mg / mL and L-menthol 10 mg / ML mixtures were prepared as test substance administration solutions, and 100 μL was administered into the oral cavity with a micropipette. As a control, 100 μL of the medium (4% CMC aqueous solution) was administered into the oral cavity.
Ten minutes after administration of the medium or test substance, the medium or administration liquid in the oral cavity was wiped with a cotton ball having a tare weight measured. The saliva secretion amount during administration was estimated by subtracting the weight of the tare and medium or test substance administration liquid from the weight after wiping.
Immediately after wiping off the intraoral medium or administration solution, a tare weight-measured cotton ball was placed in the oral cavity. In any group, the cotton balls were changed every 10 minutes, and the saliva secretion amount was measured by subtracting the weight after the replacement.

(4) Test results Table 2 and Fig. 2 show the measurement results of total salivary secretion for 30 minutes after administration of each test substance and control (vehicle) (both are n = 4), respectively.
From the figure and table, the unexpected result that the further excellent salivary secretion promotion effect | action was expressed by using L-menthol together with nicotinamide and L-aspartate sodium was obtained.

(Formulation examples 1 and 2) Toothpaste The ingredients and amounts shown in Table 3 are taken, and a toothpaste is produced according to a conventional method.

(Formulation example 3) Liquid dentifrice The ingredients and amounts shown in Table 4 are taken, and a liquid dentifrice is produced according to a conventional method.

(Formulation Example 4) Mouthwash The ingredients and amounts shown in Table 5 are taken and a mouthwash is produced according to a conventional method.

(Formulation Example 5) Oral Ointment The ingredients and amounts shown in Table 6 are taken, and an oral ointment is produced according to a conventional method.

(Formulation example 6) Gum agent The above-mentioned components and amounts shown in Table 7 are taken, and a gum agent is produced according to the section “General description of pharmaceutical preparations“ Gum agent ””.

(Formulation Example 7) Lozenges The ingredients and quantities shown in Table 8 are taken, and lozenges are produced according to the section of the Japanese Pharmacopoeia General Rules “Lozenges”.

(Formulation Example 8) Oral Spray The ingredients and amounts shown in Table 9 are used to produce an intraoral spray according to the section “General Oral Spray” in Japanese Pharmacopoeia.

(Formulation Example 9) Oral Tablets Ingredients and amounts shown in Table 10 are taken, and oral tablets are produced according to the section “General Oral Tablets” in the Japanese Pharmacopoeia.

(Formulation Example 10) Sublingual Tablets The ingredients and amounts shown in Table 11 are taken, and tablets for the oral cavity are produced according to the section of the Japanese Pharmacopoeia General Rules “Sublingual Tablets”.

(Formulation Example 11) Buccal Tablets Ingredients and quantities shown in Table 12 are taken, and tablets for the oral cavity are produced according to the section of the Japanese Pharmacopoeia General Rules “Buccal Tablets”.

(Formulation Example 12) Adhesive Tablets The ingredients and amounts shown in Table 13 are used to produce tablets for the oral cavity according to the section of the Japanese Pharmacopoeia General Rules “Adhesive Tablets”.

Claims (4)

An oral care composition containing L-aspartic acid or a salt thereof and nicotinamide. Furthermore, the composition of Claim 1 containing L-menthol. The composition according to claim 1 or 2, wherein the L-aspartic acid or a salt thereof is sodium L-aspartate. The composition according to any one of claims 1 to 3, wherein the oral care is wet in the oral cavity and / or cleaning in the oral cavity.