JP2000229863A - Composition for pharyngopathy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject pharmaceutical composition for pharyngopathy that has excellent bactericidal effect by using a combination of an iodine bactericidal agent and a compound having the buffering action in a specific pH range. SOLUTION: (A) An iodine bactericidal agent using iodine or a composite thereof with a carrier (for example, povidone iodine) in an amount of preferably 0.0001-8 wt.%, more preferably 0.03-0.5 wt.% calculated as the effective iodine, (B) a compound having the buffering action for maintaining the pH in the range from 2-5, preferably 2-3 in an amount of >=10 mM, when necessary, (C) an antioxidant, a surfactant, a taste or odor modifier and other pharmaceutically active components are used for the objective composition. As the component B, are cited a pH buffering solution, particularly a formulation of two or more kinds of pH buffer solutions. In a preferred embodiment, the pH buffer solution is, for example, citrate solution, tartarate solution or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a composition for pharyngeal diseases.

[0002]

2. Description of the Related Art Pharyngeal diseases are mainly caused by bacteria, and iodine fungicides are widely used. It is known that iodine-based bactericides have a broad bactericidal spectrum against bacteria and are relatively safe for the human body.

[0003]

At present, there are many commercially available drugs for treating pharyngeal diseases containing iodine, but there is a need for a drug having a better bactericidal effect.

[0004] It is an object of the present invention to provide a composition for an iodine pharyngeal disease having an excellent bactericidal effect.

[0005]

Means for Solving the Problems As a result of intensive studies to develop an excellent therapeutic agent, the present inventors have found that the effect is reduced in the mouth compared to the bactericidal effect outside the mouth, and that this effect is reduced. The cause was found to be pH change due to saliva and mucus in the pharyngeal mucosa. Then, when the composition for pharyngeal diseases was given a buffering action, it was found that the bactericidal efficacy of iodine was remarkably enhanced, and the present invention was completed.

That is, the present invention is a composition for pharyngeal diseases containing an iodine fungicide, which comprises a compound having a buffering action so as to have a buffering action within a pH range of 2 to 5.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, the iodine-based fungicide means iodine or a complex of iodine and a suitable carrier, and examples thereof include povidone-iodine and iodine-potassium iodide.

In the present invention, the amount of the iodine-based bactericide is preferably 0.0001 to 8% by weight, more preferably 0.03 to 0.5% by weight of the whole preparation as effective iodine from the viewpoint of bactericidal effect and feeling upon use. %.

As the buffering compound of the present invention, a pH buffering agent is preferably selected, and more preferably, a mixture of two or more pH buffering agents.

[0010] The pH buffering agent to be added to the composition for pharyngeal diseases according to the present invention means a buffering agent which can be added as a pharmaceutical additive, for example, citric acid, tartaric acid, lactic acid, malic acid, acetic acid, Examples thereof include acids such as phosphoric acid and hydrochloric acid, and pharmaceutically acceptable salts of these acids. From the viewpoint of flavor, it is preferable to select citric acid or tartaric acid or a pharmaceutically acceptable salt thereof.

[0011] The combination of two or more buffers is pH 2
5 is a combination of two or more pH buffers exhibiting a buffering action within the range of 5. D. Perrin et al.'S book, "Selection and Application of Buffer Solution" (Kodansha Scientific). Specific combinations of buffering agents include (citric acid, sodium citrate), (citric acid, sodium hydroxide), (tartaric acid, sodium hydroxide), (citric acid, sodium hydrogen phosphate), (phosphoric acid, Sodium hydroxide)
And the like.

The amount of the pH buffer is usually the concentration applied to the oropharynx, but it is preferable to add 10 mM or more in total.

The pH of the composition for pharyngeal diseases is preferably pH 2 to 3 from the viewpoint of bactericidal action.

[0014] The composition for pharyngeal diseases of the present invention is used for treatment and prevention of symptoms accompanied by sore throat and swelling.
One of the purposes of use is to disinfect the pharynx.

In addition to these additives, an antioxidant, a surfactant and a flavoring agent can be added, if necessary.

As other medicinal components, an anti-inflammatory agent, a local anesthetic, a vasoconstrictor, and the like can be blended.

As the anti-inflammatory agent, azulene and glycyrrhizic acid can be used.

[0018] Local anesthetics include ethyl aminobenzoate, lidocaine, dibucaine, procaine, meprilcaine,
Mepivacaine, bupivacaine, ropivacaine, prilocaine, etidocaine, and salts thereof (eg, hydrochloride) can be used.

Vasoconstrictors include tetrahydrozoline hydrochloride,
Nafazoline hydrochloride, phenylephrine hydrochloride, ephedrine hydrochloride, oxymetazoline hydrochloride, methylephedrine hydrochloride, epinephrine, epinephrine hydrochloride, ephedrine sulfate and the like can be used. Examples of the antioxidant include dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), propyl gallate, α-tocopherol, sodium pyrosulfite, sodium edetate and the like.

Examples of the surfactant include polyoxyethylene hydrogenated castor oil, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, polyoxyethylene polyoxypropylene copolymer, polysorbates, sodium lauryl sulfate, and sucrose. Fatty acid esters and the like.

Examples of the flavoring agent include saccharin and its salts, L-menthol, peppermint oil, eucalyptus oil, cinnamon oil, essential oils such as clove oil, components thereof, and fragrances.

The composition for a pharyngeal disease of the present invention is used in the form of a solution by a conventional method, filled in an appropriate container and applied directly to the pharynx with a cotton ball or the like, or sprayed and applied from a pump container.
It can also be used as a mouthwash.

According to the present invention, Staphylococcu
s aureus , Escherichia col
i , Pseudomonas aerginosa ,
Candida albicans , Streptoc
occus pneumoniae , Moraxell
It has become possible to provide a composition for an iodine-type pharyngeal disease, which has an excellent bactericidal effect on pharyngeal disease-causing bacteria such as a catarrhalis .

Conversely, it is possible to provide a composition for pharyngeal diseases in which the iodine taste is suppressed by reducing the amount of iodine-based fungicide to be used while maintaining the bactericidal effect.

It is difficult to mask the iodine taste with a fragrance or the like, and many people do not like it, which causes a decrease in compliance. From the viewpoint of feeling of use, the smaller the amount of the iodine-based fungicide, the better. Because it is good.
In addition, in the composition for pharyngeal diseases according to the present invention, the sourness in the mouth is maintained by the buffering action of the pH buffer, which is further advantageous in suppressing iodine taste. In particular, when using povidone-iodine, the effect of suppressing iodine taste is large, and therefore, it is preferable to use povidone-iodine as an iodine-based fungicide.

[0026]

According to the present invention, it has become possible to provide a composition for pharyngeal diseases excellent in sterilization and disinfection. In addition, since the same effect can be obtained with a smaller amount than the conventional iodine-based fungicide, it has become possible to provide a pharyngeal disease composition which is suppressed in iodine taste and excellent in feeling during use.

Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples.

Example 1 Povidone-iodine 0.45 g Concentrated glycerin 80.00 g Ethanol 15.00 g L-menthol 0.30 g Citric acid 0.50 g Sodium hydroxide 0.25 mg Purified water All 100 mL The pH is adjusted to 2.2 to obtain a stream agent.

Example 2 Povidone-iodine 0.45 g Concentrated glycerin 80.00 g Ethanol 15.00 g L-menthol 0.30 g Citric acid 1.00 g Sodium hydroxide 0.50 mg Purified water All 100 mL The pH is adjusted to 2.2 to obtain a stream agent.

Example 3 Povidone-iodine 0.45 g Lidocaine hydrochloride 0.10 g Concentrated glycerin 80.00 g Ethanol 15.00 g L-menthol 0.30 g Citric acid 1.850 g Sodium citrate 0.18 g Purified water Total 100 mL Dissolve each raw material Stream agent.

Example 4 Povidone-iodine 0.45 g Lidocaine 0.50 Concentrated glycerin 80.00 g Ethanol 15.00 g L-menthol 0.30 g Tartaric acid 3.00 g Sodium hydroxide 0.10 g Purified water 100 mL After dissolving each raw material The pH is adjusted to 2.2 with hydrochloric acid to obtain a stream agent.

Example 5 Povidone-iodine 0.45 g Glycyrrhetinic acid 0.30 g Concentrated glycerin 60.00 g Propylene glycol 20.00 g Ethanol 10.00 g Citric acid 1.80 g Sodium monohydrogen phosphate 0.15 g Purified water Total 100 mL Dissolve each raw material After that, the pH is adjusted to 2.2 with hydrochloric acid to obtain a stream agent.

Example 6 Iodine 0.5 g Potassium iodide 1.0 g Concentrated glycerin 96.00 g Ethanol 10.00 g Phosphoric acid 2.00 g Sodium monohydrogen phosphate 0.50 g Purified water A total of 100 mL And

Example 7 Povidone-iodine 7.00 g Glycerin 45.00 g Ethanol 30.00 g Menthol 0.10 g Citric acid 7.00 g Sodium citrate 0.70 g Purified water Total 100 mL Mouthwash to dissolve each raw material and dilute when used And

Comparative Example Povidone-iodine 0.45 g Concentrated glycerin 80.00 g Ethanol 15.00 g L-menthol 0.30 g Citric acid 0 g Sodium hydroxide 0 mg Purified water All 100 mL After dissolving each raw material, pH 2.2 with hydrochloric acid. To a stream agent.

Test Example 1: Test of bactericidal efficacy Example 1 and Comparative Example were doubled, sterilized and purified water twice, four times, and eight times.
Test samples were prepared by diluting 1:16, 32 *, and 64 *.

Bacterial solution 0.02 mL is added to the prepared test sample 0.5 mL, and the test solution 0.01 mL 30 seconds later.
Was transferred to 3 mL of SCDLP liquid medium, and cultured at 35 ° C. for 72 hours. The viability of the bacteria in the test solution after the culture was determined by turbidity, and the concentration at which the bacteria were killed was determined.

As the test bacteria, Pseudomonas aeruginosa I, a kind of pharyngeal pathogenic bacteria, is used.
FO13275 was used. Bacterial solution to be added to the test sample was obtained by pre-incubating in a broth for sensitivity measurement at 35 ° C. for 18 hours.
and-No. A suspension prepared to a concentration of 3 was used. The test was repeated three times, and when the results were different, the one with the larger number was adopted.

In the comparative example, no bactericidal effect was observed in the test sample diluted 4 times, but in Example 1, even the test sample diluted 32 times showed an excellent sterilizing effect.

[0040] Test Example 2: Measurement of sterilization time P. Aeruginosa was used to compare the sterilization time of the test solution of Example 1 and the test solution of Comparative Example at a 6-fold dilution concentration among the samples of Test Example 1. Bacterial solution 0.12 in 3 mL of diluent
Add 15 mL, 30 seconds, 60 seconds, 3 minutes, 5 minutes,
Take 0.01 mL after 10, 30 and 60 minutes and
The cells were cultured at 35 ° C. for 72 hours in 3 mL of DLP liquid medium.
The viability of the bacteria in the test solution after the culture was determined by turbidity, and the time at which the bacteria were killed was determined. The bacterial solution used was a bacterium cultured at 35 ° C. for 18 hours in a broth for sensitivity measurement. The test was repeated three times, and when the results were different, the one with the larger number was adopted.

In the diluted sample of the comparative example, viable bacteria were confirmed even after contact for 60 minutes or more, but in the diluted sample solution of Example 1, no viable bacteria could be confirmed even in contact for only 30 seconds.

From the results of Test Examples 1 and 2, it can be seen that the sterilizing effect of Example 1 is lower than that of the comparative example, and that the sterilizing time is shorter even with a diluent of the same concentration, and the effect is stronger.

Test Example 3 After applying about 50 μL of Example 2 or Comparative Example to the throat once, the metal-like iodine taste was evaluated. The evaluation was performed by five healthy adults who were proficient in the sensory evaluation in the oral cavity, and the administration intervals of the samples were 30 minutes or more. The order of use was randomized in consideration of the order effect of the samples. The iodine taste was evaluated according to the following five grades.
In contrast to 6, it was 1.5 in Example 2 and it was confirmed that the iodine taste was suppressed.

[0044]

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Katsuyoshi Aikawa 3-24-1, Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Kiyotaka 3-24-1, Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. F term (reference) 4C076 AA12 BB03 CC31 DD21 DD23 DD26 DD30 DD37 DD38 DD43Z DD52 DD66 EE16A FF61 4C086 AA01 AA02 FA03 HA09 MA02 MA05 MA57 NA05 ZA67 ZB35

Claims (7)

[Claims] 1. A composition for pharyngeal diseases containing an iodine-based fungicide, which comprises a compound having a buffering action so as to have a buffering action within a pH range of 2 to 5. 2. A composition for pharyngeal diseases containing an iodine-based fungicide, wherein two or more pH buffers are added to provide a buffering action within a pH range of 2 to 5. 3. The composition for pharyngeal diseases according to claim 2, wherein the total amount of the pH buffering agents is 10 mM or more. 4. The composition for pharyngeal diseases according to claim 2, wherein one of the pH buffers is citric acid or citrate. 5. The composition for pharyngeal diseases according to claim 2, wherein one of the pH buffers is tartaric acid or tartrate. 6. The composition for pharyngeal diseases according to claim 1, which has a pH of 2 to 3. 7. The composition for pharyngeal diseases according to claim 1, wherein the iodine fungicide is povidone-iodine.