JPS6361287B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an anti-inflammatory agent for the oral cavity, and more particularly to a topical preparation for treating oral inflammation that contains guaiazulene or sodium guaiazulene sulfonate as an active ingredient and has enhanced effects. Guaiazulene or guaiazulene sulfonate sodium has been traditionally used as an anti-inflammatory agent for the oral cavity as an anti-inflammatory agent with mild effects and few side effects. For example, guaiazulene is used as an oil-based anti-inflammatory agent, and guaiazulene sulfonate sodium is used as a water-soluble anti-inflammatory agent, and is widely used as a safe oral anti-inflammatory agent without irritation or side effects. has been done. However, on the other hand, because the effect is moderate,
Dramatic therapeutic effects cannot be expected. In view of these circumstances, the present inventor has conducted various studies to enhance the effects of guaiazulene and guaiazulene sulfonate sodium in oral anti-inflammatory agents, and has found that a specific surfactant may be blended with guaiazulene or guaiazulene sulfonate sodium. The inventors found that the anti-inflammatory effects of guaiazulene and sodium guaiazulene sulfonate can be significantly improved, leading to the completion of the present invention. That is, the present invention comprises guaiazulene or sodium guaiazulene sulfonate, and one or more surfactants selected from the group consisting of cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate, chlorhexidine, and chlorhexidine salts. The present invention provides an anti-inflammatory agent for the oral cavity. In the oral anti-inflammatory agent of the present invention, the anti-inflammatory effects of guaiazulene and guaiazulene sulfonate sodium are enhanced, and by taking advantage of their few side effects, it is possible to carry out extremely effective treatment of oral inflammation. Thus, the oral anti-inflammatory agent of the present invention is basically an ointment, a water solution, or a wash, which is made by combining guaiazulene or guaiazulene sulfonate sodium and the specific surfactant with a known pharmaceutically acceptable base. These are preparations in the form of oral preparations, paste preparations, medicated dentifrices, or preparations impregnated with gauze or absorbent cotton. When the base is water or a water-soluble base, it is preferable to use sodium guaiazulene sulfonate, when the base is an oily base, guaiazulene is preferably used, and when the base is an emulsifiable base, either guaiazulene or sodium guaiazulene sulfonate may be used. these are,
Generally, guaiazulene is blended in a proportion of 0.03 to 0.1% (weight %, same hereinafter) based on the total amount of the oral anti-inflammatory agent of the present invention. The surfactants used are selected from cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate, chlorhexidine and chlorhexidine salts (e.g. chlorhexidine gluconate, chlorhexidine hydrochloride, chlorhexidine acetate), which can be used alone or in combination with 2 More than one kind may be used in combination, and cetylpyridinium chloride, benzethonium chloride, and chlorhexidine gluconate are preferred because they particularly enhance the anti-inflammatory effect. These surfactants are generally used in a total amount of
It is blended at a ratio of 0.01 to 1.0%. In addition, in the anti-inflammatory agent of the present invention, from the viewpoint of enhancing the anti-inflammatory effect, the weight ratio of guaiazulene (as guaiazulene in the case of guaiazulene sulfonate sodium) to the surfactant is within the range of the above-mentioned amount. 10, preferably 1:0.5
It is desirable to set it to 5. As mentioned above, the base used may be a known base, such as water, ethanol, glycerin, propylene glycol, macrogols, water-soluble bases such as sole base, vegetable oil, lard, vaseline, paraffin, and waxes. , silicone, plastibase, mono ointment, etc., hydrophilic ointment, water-absorbing ointment, hydrophilic petrolatum, hydrated lanolin, etc., and emulsifiable bases. The oral anti-inflammatory agent of the present invention can be produced by mixing, dispersing, dissolving or emulsifying guaiazulene or guaiazulene sulfonate sodium and the surfactant in a base according to a conventional method. It can be produced by impregnating gauze or absorbent cotton with the formulation, and if desired,
Additionally, agents such as surface anesthetics (eg, lidocaine, tetracaine, ethyl aminobenzoate) can be included. Next, the present invention will be explained in more detail with reference to Examples and Test Examples. Example 1 0.05 part of guaiazulene and 0.2 part of cetylpyridinium chloride were mixed with 99.75 parts (by weight, same below) of a base consisting of 70% Plastibase and 30% sodium polyacrylate to prepare an oral antiseptic in the form of an ointment. I got an inflammatory agent. Example 2 0.05 part of guaiazulene and 0.1 part of cetylpyridinium chloride were mixed with 99.85 parts of the same base as in Example 1 to obtain an oral anti-inflammatory agent in the form of an ointment. Example 3 Guaiazulene was added to 99.9 parts of the same base as in Example 1.
An oral anti-inflammatory agent in the form of an ointment was obtained by mixing 0.05 part of the anti-inflammatory agent and 0.05 part of cetylpyridinium chloride. Example 4 0.05 part of guaiazulene and 0.1 part of benzethonium chloride were mixed with 99.85 parts of the same base as in Example 1 to obtain an oral anti-inflammatory agent in the form of an ointment. Example 5 0.05 part of guaiazulene and 0.1 part of sodium lauryl sulfate were mixed with 99.85 parts of the same base as in Example 1 to obtain an oral anti-inflammatory agent in the form of an ointment. Example 6 0.05 part of guaiazulene and 0.1 part of benzalkonium chloride were mixed with 99.85 parts of the same base as in Example 1 to obtain an oral anti-inflammatory agent in the form of an ointment. Example 7 99.85 parts of the same base as in Example 1, 0.05 parts of guaiazulene and chlorhexidine gluconate
0.1 part was mixed to obtain an oral anti-inflammatory agent in the form of an ointment. Example 8 0.05 part of sodium guaiazulene sulfonate and 0.1 part of cetylpyridinium chloride were added to distilled water.
It was mixed and dissolved in 99.85 parts to obtain an oral anti-inflammatory agent in the form of a mouthwash. Example 9 0.05 part of sodium guaiazulene sulfonate and 0.05 part of chlorhexidine were mixed and dissolved in 99.9 parts of distilled water to obtain an oral anti-inflammatory agent in the form of a mouthwash. Test Example 1 The anti-inflammatory effect of the oral anti-inflammatory agent obtained in Example 2 was tested in the following manner on gingivitis artificially caused in the oral cavity of guinea pigs. After preliminarily rearing male guinea pigs (Hartley strain) for one week at constant temperature and humidity, healthy ones weighing approximately 280 g were used for testing, with 15 in each group and 60 in 4 groups. Under pentobarbital anesthesia according to the method of Yoshikawa et al., puncture wounds were made at 6 locations with a hypodermic needle, and an insoluble gelatin sponge impregnated with croton oil was applied for 20 minutes to create artificial gingivitis. Inflammation was observed at 24-hour intervals after the onset of inflammation, using swelling as an indicator. Inflammation was determined using the method of Yoshikawa et al., which was a partial modification of the PMAindex method, and the gingival region was divided into 6 sections, and the degree of swelling in each section was evaluated using the following 5-level criteria. The degree of inflammation was expressed by the total score. 0: Normal 1: Slightly swollen 2: Clearly 〃 3: Quite 〃 4: Very 〃 Three times in total at 24, 48, and 72 hours after the inflammation treatment; 0.2 g of the test drug was injected into the gingival area. Apply under barbital anesthesia, 24 hours after onset of inflammation, i.e. the first
The recovery rate was calculated using the following formula based on the degree of inflammation immediately before the first application of the drug. Recovery rate (%) = (1 - degree of inflammation at each observation/degree of inflammation 24 hours after onset of inflammation) x 100 The results are shown in Table 1.

[Table] As shown in Table 1, the oral anti-inflammatory agent of the present invention containing guaiazulene and a surfactant has a much higher anti-inflammatory effect than guaiazulene alone. In addition, in the controls, etc., the recovery rate increases with time, but this is due to natural recovery. Test Example 2 Similarly to Test Example 1, the anti-inflammatory effects of the oral cavity anti-inflammatory agents of Examples 1 to 3 were tested. The results are shown in Table 2.

【table】

[Table] Test Example 3 In the same manner as Test Example 1, the anti-inflammatory effects of the oral anti-inflammatory agents of Examples 4, 5, and 7 were tested. The results are shown in Table 3.

【table】

[Table] The results in Table 3 also show that the anti-inflammatory effect of guaiazulene is enhanced by using the specific surfactant. Comparative test test agent (1) Contains guaiazulene (0.05%) (2) Contains guaiazulene (0.05%) + cetylpyridinium chloride (0.1%) (anti-inflammatory agent of the present invention) (3) Guaiazulene (0.05%) + polysorbate
Contains 80 (0.1%) (4) Contains polysorbate 80 (0.1%) (5) Base only The base consists of 70% plastibase and 30% sodium polyacrylate, and (1) to (4) are the base and each Prepared by mixing the ingredients. Method: Male guinea piglet (Hartley strain) weighing approximately 250g.
The anti-inflammatory effect was tested in the same manner as in Test Example 1 using 5 groups of 50 animals (10 animals per group). Observations were conducted for 7 days. The results are shown in Table 4.

【table】

[Table] As shown in Table 4, the oral anti-inflammatory agent of the present invention containing guaiazulene and the surfactant showed a significant effect, but the combination of polysorbate 80 did not show any effect.

Claims (1)

[Claims] 1. Guaiazulene or sodium guaiazulene sulfonate, cetylpyridinium chloride,
An anti-inflammatory agent for the oral cavity, characterized in that it contains one or more surfactants selected from the group consisting of benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate, chlorhexidine, and chlorhexidine salts. 2 Guaiazulene or guaiazulene sulfonate sodium as guaiazulene 0.03~
0.1% by weight, total 0.01-1.0% by weight of the surfactant
The anti-inflammatory agent for the oral cavity according to item 1 above.