JPS60188316A - Anti-inflammatory for oral cavity - Google Patents

Abstract

PURPOSE:The titled anti-inflammatory that contains a combination of guaiazulene or its sodium sulfonate salt with a specific surface active agent, thus showing enhanced anti-inflammatory effect without side-effects. CONSTITUTION:The objective agent is composed of guaiazulene or sodium guaiazulenesulfonate and surface active agents selected from chloroacetyl pyridinium, benzethonium chloride, benzalkonium chloride, sodium laurylsulfonate, chlorhexidine, and chlorhexidine salts. The amounts of both components are 0.03-1wt% in the anti-inflammatory component (calculated as guaiazulene) and 0.01-1.0wt% in the surfactant respectively, preferably at a weight ratio of 1:(0.5-5) the anti- inflammatory to the surfactant.

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 the treatment of oral inflammation that contains guaiazulene or sodium guaiazulene sulfonate as an active ingredient and has enhanced effects.

Guaiazulene or sodium guaiazulene sulfonate has been traditionally used as an anti-inflammatory agent for +-+ II/p as an anti-inflammatory agent with less adverse effects and fewer side effects. For example, oil-based anti-inflammatory agents use guaiazulene, while water-soluble 14121 anti-inflammatory agents use guaiazulene sulfone-1.sulfonate, which has irritation 1f1 and side effects. 4i Widely used as an oral anti-inflammatory agent.

However, on the other hand, its effectiveness is less than 1. 'c'/,
- Therefore, dramatic therapeutic effects cannot be expected.

In view of these circumstances, Suiben Akashi has conducted various studies to enhance the effects of guaiazulene and guaiazulene sulfonate sodium in single-cavity anti-inflammatory agents. The present invention was completed after learning that the anti-inflammatory effects of guaiazulene and sodium guaiazulene sulfonate can be significantly improved by incorporating them.

Specifically, the present invention provides guaiazulene or guaiazulene sulfonate sodium, cetylpyridinium chloride, benzene chloride, benzalkonium chloride,
One or two selected from the group consisting of sodium lauryl sulfate, chlorhexidine, and chlorhexidine salts.
The present invention provides an anti-inflammatory agent for the oral cavity, which contains at least one surfactant. 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 basically consists of an ointment, a water solution, or a solution, which is formed by combining guaiazulene or guaiazulene sulfonate sodium and the specific surfactant with a known pharmaceutically acceptable base. These are preparations in the form of mouthwashes, 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 generally include the oral anti-inflammatory agents of the present invention, such as guaiazulene, C), 03-0
．． It is blended at a ratio of 1% (weight %, hereinafter the same).

The surfactants used include cetylpyridinium chloride, benzethonium chloride, benlyyl]nium chloride, sulfur-lium lauryl sulfate, chlorhexidine salts (for example, chlorhexidine salts) -1-1IP Fi! Chlor to 1 Nisidine, Acid-resistant chlorhexidine), etc.), these are class A or may be used in combination of two or more, The anti-inflammatory effect is greatly enhanced by Le\\xysingle] Nee1! It is preferable because

These surfactants are generally mixed in a total amount of 0.01 to 160% with respect to the total amount of the oral anti-inflammatory agent of the present invention.

In addition, in the anti-inflammatory agent of the present invention, from the viewpoint of enhancing the anti-inflammatory effect, the ratio of guaiazulene (as guaiazulene in the case of guaiazulene sulfonate sodium) to the surfactant is set within the above-mentioned range of blending amount to 1:0. .1~1
0, preferably 1:0.5-5.

As mentioned above, the base used may be a known base, such as water, ethanol, glycerin, propylene glycol, ncrogols, water-soluble bases such as sole base, vegetable oil, liver fat, vaseline, paraffin, waxes, etc. Examples include oily bases such as silicone, plastibase, simple ointment, etc., hydrophilic ointments, water-absorbing ointments, emulsifiable bases such as parent petrolatum, hydrated lanolin, etc.

The oral anti-inflammatory agent of the present invention can be produced by mixing, dispersing, dissolving, and emulsifying guaiazulene or guaiazulene sulfone 1 to 1 helium and the surfactant in a base according to a conventional method; It can be produced by impregnating a liquid preparation into a gauze or absorbent cotton according to a conventional method, and if desired, a surface anesthetic (for example, lidocaine, tetrahydro-5-yne, diaminobutylene), etc. can be added. It is also possible to mix drugs.

Next, the present invention will be explained in detail with reference to Examples and Test Examples.

Example 1 0.05 part of guaiazulene and 0.2 part of cetylpyridinium chloride were added to 99.75 parts (by weight, same hereinafter) of a base consisting of 70% plastibase and 30% sodium to lithium polyacrylate. Rolo-P is mixed into an ointment form.
Also, take an anti-inflammatory agent.

Example 2 Same base as Example 1 99.8! 0.05 part of guaiazulene and 110.1 parts of cetylpyridinilla chloride were mixed with part i to obtain an oral anti-inflammatory agent in the form of an ointment.

Example 3 99.9 parts of the same base as in Example 1 and 0.0 parts of guaiazulene.
0.05 parts of cetylpyridinium chloride and 0.05 parts of cetylpyridinium chloride were mixed to obtain an oral anti-inflammatory agent in the form of an ointment.

-〇- Example 4 99.85 parts of the same base as Example 1 and 0 guaiazulene
．． An anti-inflammatory agent for the oral cavity in the form of an ointment was obtained by mixing 0.05 parts and 1 to 0.1 parts of benzene chloride.

Example 5 99.85 parts of the same base as in Example 1 and 0 guaiazulene
．． 0.5 parts of sodium lauryl sulfate and 0.1 part of sodium lauryl sulfate were mixed to prepare an oral anti-inflammatory agent in the form of an ointment.

Example 6 99.85 parts of the same base as in Example 1 and 0 guaiazulene
．． Mix 0.05 parts of benzalkonium chloride and 0.1 part of benzalkonium chloride to prepare an oral anti-inflammatory agent in the form of an ointment.

Example 7 99.85 parts of the same base as in Example 1 and 0 guaiazulene
．． 0.5 parts of chlorhexidine gluconate and 0.1 part of chlorhexidine gluconate were mixed to obtain an oral anti-inflammatory agent in the form of an ointment.

Example 8 0.05 part of guaiazulene sulfone-su[-lium and 11 parts of dichloropyridinium chloride were added to 99.9 parts of distilled water.
The anti-inflammatory agent for oral cavity was mixed and dissolved in 85 parts and washed.

Example 9 An anti-inflammatory agent for the oral cavity in the form of a cleanser by mixing and dissolving 0.05 parts of guaiazulene sulfone-1-1-1-lium and 0.05 parts of chlorhexidine in 99.9 parts of hot water. 1
It's q.

Test Example 1 The anti-inflammatory effect of the oral anti-inflammatory agent obtained in Example 2 was tested in the following manner on artificially induced gingivitis in the oral cavity of a guinea pig.

1 to 1 male guinea pig (Hartley strain) at constant temperature and humidity
After preliminary rearing for a week, healthy animals weighing 280 q were subjected to the test, and the test was conducted with 60 animals in 4 groups of 11Y15.

Under bendoparbital 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 chlorine oil was applied for 20 minutes to produce artificial gingivitis.

Inflammation was observed at 24 hour intervals after the onset of inflammation using swelling as an indicator. Inflammation was determined by dividing the gingival region into 6 sections using the method of Yoshikawa et al., which was a partial modification of the method of P, M, A, 1nd, y: The degree of swelling for each fraction was determined as follows: The degree of inflammation was expressed by the total score evaluated according to the grade criteria.

O: Normal 1: Slightly swollen 2: Clearly 3: Significantly 4: Extremely inflamed 3 times at 24.48 and 72 hours after treatment; Bendoparbital 0.2g of test drug was applied to the gingival area. The drug was applied under anesthesia, and the recovery rate was calculated using the following formula based on the degree of inflammation 24 hours after the onset of inflammation, that is, immediately before the first drug application.

9- Flame ′J1i−culm rσ at each observation time Recovery rate - (1-5X100 (%) 240A after inflammation 1iil Eye inflammation culm 1α The results are shown in Table 1'? i.

10- 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 controls, etc., the recovery rate was higher due to menstruation, but this was due to natural recovery.

Test Example 2 In the same manner as Test Example 1, the inflammatory effects of the anti-inflammatory agents for piles for ITI cavities of Examples 1 to 3 were tested. The usage is shown in Table 2.

-10- 13- 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.

14- 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) Guaiazulene ((1.05%)) - Cedylviridinium chloride
(0.1%) containing (anti-inflammatory agent of the present invention) (3> Guaiazulene (0.05%) + polysorbate 1
〜8(') (0,1%) containing (4) Polysolvay 1.80 ((3,'1%) containing (5
) Base only The base consisted of 70% Plusdibase and 30% sodium polyacrylate, and (1) to (4) were prepared by mixing the base and each component.

Method The anti-inflammatory effect was tested in the same manner as in Test Example 1 using 50 groups of 5 groups of 10 E11 guinea pigs (Bar 1-Ray strain) with a body size of about 250 a. Observations were conducted for 7 days.

The results are shown in Table 4.

17- 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.

Patent applicant: B Brand Medicodenta I Co., Ltd., patent attorney, Aoyama Hajime, and two others 19- 18-

Claims (2)

[Claims] (1) Contains guaiazulene or sodium guaiazulene sulfonate and one or more surfactants selected from the group consisting of cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, sulfurium lauryl sulfate, chlorhexidine, and chlorhexidine salt. An oral anti-inflammatory agent characterized by: (2) Guiazulene or guaiazulene sulfonate sodium as guaiazulene 0°03 to 0.1
The anti-inflammatory agent for the oral cavity according to item (1) above, which contains the surfactant in a total amount of 0.01 to 1.0% by weight.