JPS5822009B2 - Method for removing bitterness from oral chlorhexidine preparations - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to a method for removing bitterness from oral preparations containing chlorhexidine digluconate.

Chlorhexidine (hereinafter abbreviated as CHDG) Ha1,1
'-hexamethylenebis(5-<4-chlorophenyl)
This is a biguanide compound called "Biguanide", and its properties are as introduced in the Merck Index, 7th edition, page 236, but it has a long-lasting bactericidal effect in a wide range of fields, so it is effective against bacterial diseases. It is attracting attention as a preventive agent, preservative, disinfectant, deodorant, and anti-inflammatory agent.

However, the water solubility of CHDG is extremely low, and despite its usefulness, it has the disadvantage of being difficult to use for general purposes.Therefore, some kind of improvement was sought, and it was discovered that CHDG was treated with polyhydroxy aliphatic carboxylic acids (especially gluconic acid). It has been found that when
Its practical value is quite high.

However, as the water solubility of CHDG improves and the range of its application as an aqueous solution expands, various disadvantages are becoming more apparent.

One of them is the bitter taste when applied to the oral cavity.

In other words, since CHDG has the above-mentioned effects, it is expected to be useful as a main agent or an adjunct in oral cleansers, such as oral bactericides, anti-inflammatory agents, anti-plaque agents, etc.; Possible examples include mouthwashes, liniments, lozenges, and toothpastes.

For example, the Journal of the Oral Hygiene Society, Vol. 24, No. 1, No. 19-2.
On page 3 (1971), examples of the use of CHDG-containing mouthwashes and liniments are reported, and it can be seen that they have a remarkable plaque-inhibiting effect (therefore, caries-preventing effect).

Furthermore, it has recently been reported that CHDG is effective in treating aphthous ulcers as a new effect in the oral cavity.

For these reasons, although CHDG-containing oral preparations should be widely used, CHDG, especially its highly water-soluble salt CHDG digluconate, has a strong bitter taste, so it is not often used as oral preparations. It has not yet reached the point where it is done.

The present invention has been made in view of these circumstances, and its purpose is to provide a method for eliminating the bitter taste of oral chlorhexidine preparations as much as possible.

The gist of the structure of the present invention that has achieved the above object is that 0.2 parts by weight or more of lactic acid is blended per 1 part by weight of chlorhexidine digluconate in the oral chlorhexidine preparation. It is something.

One of the most rudimentary measures that can be considered to reduce the bitterness of CHDG is to mask the bitterness by incorporating sweeteners such as sugar.

However, with low concentration solutions containing CHDG digluconate, we were able to obtain sufficient bitterness reduction effects with sweeteners and sugars, whereas in relatively high concentration solutions aimed at oral sterilization and plaque control, CHDG The characteristic bitterness could not be removed.

Moreover, this method is not very recommended for oral cavity cleansers whose main purpose is to prevent dental caries.

Therefore, by using menthol, peppermint, pepper oil, etc., which are commonly used as mouth fresheners, C.
Considering suppressing the bitter taste of HDG, we first investigated the solubility of the above-mentioned coolant in solvents such as polyethylene glycol (PEG) and ethanol, but in both cases, PE
It was found that the solubility in G is extremely low, and that ethanol is convenient as a usable solvent.

Based on this result, CH
A DG rinse agent was prepared and its bitter taste removal effect was investigated.

Prescription I CHDG 1 d, l-menthol (synthetic product) 0.3 Ethanol (pharmacopoeia) 35 Water Total remaining amount 100 (parts by weight) Prescription 2 CHDG 1 Penogu-mint essence 0.6 Ethanol (pharmacopoeia) 35 Water Total remaining amount: 100 (parts by weight) Since the mouth-containing agents obtained in Formulation 1 and Method 2 are undiluted solutions,
Add water to 2ml of this stock solution to make a total volume of 101fLlC
The concentration of HDG was 0.2), and a sensory test was conducted on a panel of 10 people selected at random, and the results shown in Table 1 were obtained.

That is, although Formulation 2 was slightly superior in terms of cooling sensation, it was found that in any case, the bitterness of CHDG could not be sufficiently masked.

Note that even if the amount of the cooling agent added was further increased, no particularly significant results were obtained.

Therefore, the present inventors investigated methods of suppressing bitterness using other additives, using various flavoring agents (for example, acids such as citric acid, etc.).
were selected and experiments similar to those described above were conducted for each of them, but lactic acid, which itself does not have a bitter taste, was found to be most effective, so the case where lactic acid is added will be described below.

Tables 2 to 4 show the changes in bitterness and sourness when the concentration of CHDG used and the amount of lactic acid blended were changed.
All of these are the average results of the sensory tests conducted by the 10-person panel.

; As is clear from the results in Tables 2 to 4, the bitterness of CHDG without the addition of lactic acid is extremely pronounced, but as the amount of lactic acid added increases, the bitterness gradually decreases, and eventually becomes almost completely bitter. It's like I can't feel it anymore.

On the other hand, it is noteworthy that the sourness caused by the addition of lactic acid does not necessarily increase in response to the decrease in bitterness, but rather that only the bitterness decreases without producing any sourness initially.

And the amount of lactic acid required to achieve substantial suppression of bitterness is C
Although it varies slightly depending on the concentration of HDG and is not necessarily strictly regulated, a general oral preparation of 0.2
It is considered that parts by weight or more are preferable.

In addition, the concentration of CHDG generally used in the destaining agent for preventing bacterial plaque, which has recently been attracting attention, is 0.1 to 0.5, so CHD
It is recommended that 0.2 parts by weight or more (more preferably 0.4 parts by weight or more) of lactic acid be blended with respect to GI parts by weight.

On the other hand, although this is the upper limit of the amount of lactic acid to be blended, since lactic acid itself has a pleasant sour taste, even if a slightly larger amount is blended, it will not cause discomfort to the user.

Therefore, there is virtually no upper limit, but considering the initial purpose of reducing bitterness and economic efficiency, the upper limit should be set at around 0.8 to 1.6 parts by weight. good.

Oral preparations to which the method of the present invention can be applied include mouthwashes, liniments, troches, toothpastes, etc., and it goes without saying that in addition to simply being used as an aqueous solution, a suitable base material may also be used.

It goes without saying that other ingredients may be added depending on the intended use.

Examples of the third component include oral preparation components other than CHDG, such as antibacterial agents known as plaque inhibitors, anti-inflammatory agents, and refreshing agents.

As a formulation example in which such a third component was added, the following formulation was prepared and subjected to the same sensory test as described above.

The results regarding bitterness and sourness are shown in Tables 5 and 6, and are almost the same as the results shown in Tables 2 and 3.
Since l-menthol and ethanol are blended, the fragrance and refreshing feeling are further improved, making it even more convenient as a rinsing agent.

From this point of view, the following formulation examples can be presented as examples of the present invention.

Formulation 3 CHDG O,1 Lactic acid (Pharmacopoeia) 0.02 Ethanol (Pharmacopeia) 7 Water Total remaining amount 100 (parts by weight) Formulation 4 CHDG O,2 Lactic acid (Pharmacopoeia) O,OS Ethanol (Pharmacopoeia) 7 Water Residual Total amount 100 (parts by weight) Prescription 5 CHDG O,4 Lactic acid (pharmacopoeia) 0.2 Ethanol (pharmacopoeia) 7 Water Total amount remaining 100 (parts by weight) Prescription 6 CHDG O,1 Lactic acid (pharmacopoeia) 0. 04 d, l-menthol (4 meals) 0.06 ethanol (
Pharmacopoeia) 7 Water Total remaining amount 100 (parts by weight) Prescription 7 CHDG O,2 Lactic acid (Pharmacopeia) 0.12 d, l-menthol (Combined) 0.06 Ethanol (Pharmacopeia) 7 Water Total remaining amount 100 (Parts by weight) The rate of inhibition of dental plaque formation was investigated using the rinsing agent obtained from Formulation 7 of the above formulations (20 adult subjects).

At this time, the gargling agent of Formulation 7 was spread into the mouth for 5 to 30 seconds twice a day and then exhaled, but the aftertaste was not bad even without gargling (with tap water) afterwards.

When we conducted a test similar to that described in the above-mentioned Journal of the Oral Health Society, we were able to confirm the same plaque-inhibiting effect.

Since the method of this invention is configured as described above, the CE
The bitter taste of DG has almost disappeared, and the aftertaste after applying rinsing etc. is not bad.

Therefore, it can be used continuously without being disliked, especially by people with strong tastes such as school children and young people, so it will greatly contribute to oral hygiene measures in Japan, especially caries prevention measures. There is.

Claims (1)

[Claims] 1. A method for removing bitterness from a chlorhexidine preparation for oral use, which comprises blending 0.2 parts by weight or more of lactic acid with respect to 1 part by weight of chlorhexidine digluconate in the chlorhexidine preparation for oral use.