KR20060012232A - Tongue-cleansing preparations for removing oral malodor - Google Patents

Abstract

The present invention relates to a deodorant tongue cleaner having a long-term deodorant effect by applying a short-term application, and provides a deodorant tongue cleaner comprising one compound selected from the group consisting of tinidazole and metronidazole as an active ingredient.

The detergent according to the present invention is an excellent bad breath remover that is simple to use and has a short application period of about a week while the bad breath removing effect lasts for about a month or more.

Deodorant, External preparation, Tinidazole, Metronidazole, Dexamethasone, Suspension

Description

Tongue-cleansing preparations for removing oral malodor}

The present invention relates to a tongue cleaner having excellent long-term excellent bad breath removal effect by cleaning the tongue for a short time.

Bad breath, which can be defined as odors coming from the oral cavity or nasal passages, or an unpleasant odor from the mouth, causes many problems in interpersonal relationships that offend the other person. If you smell something in your mouth, you may be offended by your bad breath, so you may not be able to communicate with confidence and talk enough. Therefore, in a modern society where interpersonal relationships are becoming more and more important, in particular, people with many interpersonal occupations may have problems in social life. If this process continues, personality can become introspective and, in extreme cases, can cause extreme popularity. Bad breath is not only a serious impediment to maintaining good interpersonal relationships, but also a detriment of the value of self-awareness and quality of life. Even in advanced economies leading the cleanliness, it is estimated that more than 50% of the population suffers from bad breath. Moreover, no other person is completely free of bad breath in the rest of the population, and humans have known the problem of bad breath since their appearance on Earth.

The main causes of bad breath are volatile sulfur compounds such as hydrogen sulfide (H ₂ S), methylmercaptan (CH ₃ SH) and small amounts of dimethyl sulfide (CH ₃ SCH ₃ ) produced by anaerobic bacteria parasitic in the tongue and developed tongue It is known to be caused by chemicals such as cadaverine and isovaric acid. In addition, cleanliness in the mouth, periodontal disease and dry mouth may be the cause.

Most of the bad breath is bad breath caused by oral or systemic causes, and pathogenic bacteria are the essential factors of bad breath. More than 80 oral bacteria identified in subgingival plaque have been studied, and they are known to produce the above volatile sulfur compounds which cause bad breath. Such pathogenic bacteria, in particular, anaerobic bacteria include Fusobacterium , Bacteroides fundiliformis , Capnocytophaga , Veillonella , Krebsiella pneumoniae ( Klebsiella pneumoniae ) and the like are known.

Representative oral areas that cause bad breath are the tongue and the subgingival. Of these, the tongue is the most important site and is known to cause about 60% of bad breath. The most important of these is the rear 1/3 of the tongue. If you look at the posterior side of the tongue and you have a white fetus, it means that anaerobic bacteria have multiplied and sulfur compounds are deposited between the teats, causing chronic bad breath. The smell from the back of the tongue is quite different from the smell from subgingival plaque. That is, in the oral cavity, the smells generated from different parts have different characteristics of the smells.

Conventional bad breath treatment methods include: cleaning the tongue with antimicrobial dentifrice, Tongue scraping, Tongue cleansing with Ultrasonic scaler, periodontal treatment including tartar removal, Oral diseases such as dental caries and dry mouth. Among these treatments, direct tongue treatment involves cleaning the tongue with antibacterial dentifrices, scratching the tongue with an instrument, and washing the tongue with an ultrasonic demagnetizer. The latter two methods suggest that patients use special instruments. In addition to the inconvenience in use, the therapeutic effect is also short-term disadvantage.

Drugs used to clean the tongue with antibacterial dentifrice include 0.2% chlorhexidine, cetylpyridium chloride, benzenetonium chloride, phenolic flavor oil, zinc acetate, zinc chloride, and chlorine dioxide. . However, when the tongue is washed with this dentifrice, its working time is generally known to be about 8 hours, which is not only inconvenient to clean several times daily for continuous bad breath removal, but also has the disadvantage of incomplete effects in the bad breath removing effect. have. The reason is that these methods are merely a method of incompletely inhibiting the microorganisms rather than completely killing the microorganisms causing bad breath. Bad breath specialists accept that some unpleasant bad breath is inevitable, and even if patients are rejected for treatment because there is no abnormality in mechanical measurements or connoisseur's diagnosis, patients often suffer from bad breath.

Recently, a formulation with metronidazole added to a chewing gum including a bismuth derivative has been filed (patent application No. 10-1999-7003823) in connection with bad breath removal. However, metronidazole in addition to this chewing gum has been described as a more effective killer of Helicobacter pylori, which, together with bismuth derivatives, is present in the oral cavity and gastrointestinal tract, causing ulcers. The antimicrobial effects of bismuth and metronidazole against pylori are well known. The application does not show anywhere the inhibitory effects of metronidazole on bad breath. However, only the inhibitory effective concentration of the bismuth derivatives against the microorganisms of bad breath was investigated and the bad breath inhibitory effects of the chewing gum containing the bismuth derivatives were presented ("Summary of the Invention", "Detailed Description", and " Example 11 ").

In addition, according to recent publications ( European Journal of Internal Medicine 2003; 14: 45-48, Scientific American 2002; 286/4: 58-65), patients infected with the gastrointestinal tract by Helicobacter have bad breath and are treated with antimicrobial agents It is recommended to wear for 4 weeks. However, in the case of oral medicine, the side effects as well as the effect is a problem, it is true that countless people who are not infected with Helicobacter suffer from bad breath. Therefore, there is an urgent need in the art for an easy-to-use and short-term application of a bad breath remover that can continuously remove unpleasant bad breath for a long time regardless of the cause.

On the other hand, it is also important to remove bad breath with a small amount of the drug, but it is also important to know how long the inhibitory effect persists after the application of the drug. Also, the side effects should be considered. As a method of measuring the effect of the bad breath remover, mechanical measurement methods such as measuring the concentration of volatile sulfur compounds in the oral cavity or testing the bacteria in saliva are mainly used.In this case, psychological factors do not affect the mechanical measurement. Tends to complain of bad breath. Therefore, it is also possible to take a breath directly, or rub the needle and tongue into the fingertips and rub it. Inspection is actually more convincing than mechanical measurement.

It is an object of the present invention to provide a tongue cleaner which can remove bad breath to a satisfactory level for a long time by applying directly to the tongue for a short time.

Bad breath treatment experts have never thought of using nitroimidazole-based drugs such as Tinidazole or Metronidazole for the purpose of eliminating bad breath, and also using a pharmaceutical preparation in the form of an external cleanser I did not think that it could completely kill microorganisms causing bad breath. However, the present inventors have continued their research on the treatment of bad breath, and as a result of the conventional antifungal If nitinimidazole-based drugs such as tinidazole or metronidazole, which have been used in the internal medicine, gynecology, dermatology or dental field, are used as tongue cleaning agents for deodorant, they can be applied to the patients for a relatively short period of time. It has been found that it has a long-term bad breathing effect. It has also been found that tinidazol or metronidazole can be used in combination with dexamethasone to have a relatively long-term deodorant effect in a relatively short time. The present invention has been completed based on this finding.

In particular, the tongue cleaner of the present invention can be applied to the tongue easily at home by the patient in a very simple manner, which is convenient and can remove bad breath to a very good extent for a long time only by washing the tongue for a short time.

In order to achieve the above object, the present invention provides a deodorant tongue cleaning agent comprising a compound selected from the group consisting of tinidazole and metronidazole as an active ingredient.

The tongue cleaning agent for removing bad breath according to the present invention may further include dexamethasone. Accordingly, the present invention provides a tongue cleaner in which tinidazole or metronidazole and dexamethasone are combined.

The present invention also provides tongue cleaners containing 1.5 to 3.0% tinidazole or metronidazole and 0.2% to 0.4% dexamethasone relative to the total detergent weight.

Nitroimidazole-based chemotherapeutic agents comprising tinidazole or metronidazole according to the present invention have been used in various formulations in the fields of medicine, obstetrics, dermatology and dentistry, but as a tongue cleaning agent for the purpose of eliminating bad breath as in the present invention It has never been introduced that it can be used. Tinidazole is susceptible to microorganisms such as anaerobic bacteria, trichomonas, amoeba, etc., thus, those skilled in the art will understand that (semi-synthetic) antimicrobial agents having a similar spectrum exhibit similar long-term bad breath inhibitory effects as in the present invention.

Tinidazole, metronidazole or dexamethasone, which are active ingredients of the tongue cleaning agent according to the present invention, may be prepared according to various manufacturing methods known in the art, and domestic pharmaceutical companies that provide raw materials (eg, tinidazole of Youngpoong Pharm. Metronidazole of Hanil Pharmaceutical and Dexabetason of Youngjin Pharmaceutical).

When applying the tongue cleaner comprising tinidazole or dexamethasone according to the present invention to the tongue, the tinidazole or dexamethasone component is adsorbed on the tongue of the tongue and is then covered with saliva and has low solubility and gradually disappears from the tongue. In addition, when applying the tongue cleaning agent according to the present invention further comprises dexamethasone to the tongue, the tongue is overdeveloped and keratinized due to some stimulation, dexamethasone adsorbed on the tongue is reduced the hair papillae to cause bad breath causing microorganisms Reduces breeding.

According to one preferred embodiment according to the present invention, the tongue cleaner of the present invention is applied to bad breath due mainly to the development of tongue and tongue. The tongue cleaning agent of the present invention not only has a bactericidal action directly while rubbing the tongue, but also the bacterium microorganisms on the tongue, which are susceptible to the disintegrating of the teat edinidazole or metronidazole suspension for a relatively long time (more than about 30 minutes) at low doses. Concentrations that can inhibit the stay on the tongue can be sustained action.

According to another preferred embodiment of the present invention, the content of tinidazole and dexamethasone included in the tongue cleaner of the present invention is 1.5% to 3.0%, preferably 2.0% to 2.5% of tinidazole, based on the total weight of the cleaner. , More preferably, it is 2%, dexamethasone is 0.2%-0.4%, Preferably it is 0.2%-0.3%, More preferably, it is 0.2%. Similarly, metronidazole included in the tongue cleaner of the present invention containing metronidazole and dexamethasone; The content of dexamethasone is 1.5% to 3.0%, preferably 2.0% to 2.5%, more preferably 2%, and dexamethasone 0.2% to 4.0%, preferably 0.2% to 0.3%, based on the total detergent weight. More preferably, it is 0.2%. Thus, according to the most preferred embodiment of the present invention, the detergent is a 2.0% / 0.2% suspension made of 100 ml, for example, 2.0 g of tinidazole or metronidazole and 0.2 g of dexamethasone in suspension in distilled water.

In preparing the tongue cleaning agent according to the present invention comprising as an active ingredient a compound selected from the group consisting of tinidazole and metronidazole, an effective amount of tinidazole or metronidazole is first added to distilled water and then shaken to disperse. In addition, in the case of preparing a tongue cleaner further comprising dexamethasone, an effective amount of tinidazole or metronidazole and dexamethasone is added to distilled water and then shaken to disperse. At this time, in some cases, pharmaceutical adjuvants such as suspending agents or sweeteners may be added to facilitate suspension and reduce rejection when the patient is applied to the tongue.

The tongue cleaner according to the invention thus prepared may be in the form of a suspending agent or gel, preferably a suspending agent.

In addition, the particle diameter of the produced | generated suspension is made into about 1/20000 cm-1/1000 cm.

In using the tongue cleaning agent according to the present invention, first, as a pretreatment, the teeth are wiped clean, and the toothpaste on which food is adsorbed is well wiped with a toothbrush moistened with a conventional toothpaste. Thereafter, 4 drops of the detergent of the present invention (approximately 3 mg as tinidazole) were added dropwise to a new toothbrush, and then the entire back portion of the tongue was inserted deeply into the tongue, especially the toothbrush, and the rear 1/3 of the tongue was evenly distributed. Rub sincerely for 5 minutes, then rinse lightly once with water. In some cases, instead of washing with water, you can simply spit two or three times. Toothbrushes are soft, but rather strong, thinning is desirable. Do not eat food within 1 hour after application. In this way the tongue is washed twice a day for seven days after breakfast and before bedtime using the cleaning agents of the present invention.

After using the detergent of the present invention for 7 days, the use was stopped, and after breakfast and dinner, the effect was observed by sensory examination before dinner, while gently wiping the food adsorbed on the tongue with ordinary toothpaste.

As mentioned above, the best way to realistically measure bad breath in a patient's position is by the human sense of smell. It is clinically recognized that there is considerable agreement between the judgments of bad breathers on the presence of bad breath (Rosenberg etc., 1991 a, b; Rosenberg and McCulloch, 1992). In approximately nine out of 14 patients who applied for each deodorant test, no unpleasant bad breath recognized by themselves or their connoisseurs was detected for a prolonged period of more than 30 days. Confirmed. Approximately five remaining failures to treatment have been presumed to have been due to inadequate application of the cleaning agents of the invention or to re-infection from others or from reflux of the stomach. The volunteers were those who had no special dental and otolaryngological illnesses, who both recognized themselves and others. From the deodorization experiments, it was found that bad breath did not recur unless the bad breath-causing microorganisms completely killed on the tongue were not reinfected from saliva of others.

Since the cleaning agent of the present invention is an external preparation, the side effects of its use are minimized, and the bad breath-causing microorganisms are completely killed, so the bad breath treatment effect is semipermanent unless it is infected again. This formulation was applied to the tongue for about 3 to 5 minutes and then rinsed the mouth with water and only 7 days of use did not show any side effects and no shifts. In addition, if it contains more than 2.0% of tinidazole or metronidazole or dexamethasone, it is a very thin tongue cleaning agent of 2.0% / 0.2%, and the amount remaining after being taken out is washed away, so the amount absorbed into the body is negligible. The side effects and toxicity caused by trace amounts of bartinidazole or metronidazole and dexamethasone are rarely a problem.

Hereinafter, the present invention will be described in more detail with reference to specific examples of the present invention. The scope of the present invention should not be construed as being limited only to these examples from the examples described below, and those skilled in the art can use the cleaning agents of the present invention modified and substituted within the scope of ordinary skill based on these examples. It will be understood that such modifications and substitutions are also within the scope of the invention as claimed in the claims herein.

Example 1 Preparation of Deodorizing Cleaner Containing Tinidazole

2.0 g of tinidazole (purchased from Yeongpung Pharmaceutical Co., Ltd., 98.5% or more as tinidazole upon drying) was suspended in distilled water to a final volume of 100 ml to obtain a 2.0% suspension of tinidazole. The suspension of this suspension was obtained by separation using a centrifugal separator (Combi-514R, Hanil Science Industry Co., Ltd.) and the particle diameter of the suspension was approximately 1/20000 cm to 1/1000 cm.

Example 2 Preparation of Deodorizing Cleaner Combining Tinidazole and Dexamethasone

Tinidazole (purchased at Yeongpung Pharmaceutical, more than 98.5% as tinidazole when dried) and 0.2 g of dexamethasone (purchased at Yeongjin Pharm.) Are suspended in distilled water to a final volume of 100 ml. A% / 0.2% suspension was obtained. The suspension of this suspension was obtained by separation using a centrifugal separator (Combi-514R, Hanil Science Industry Co., Ltd.) and the particle diameter of the suspension was approximately 1/20000 cm to 1/1000 cm.

Examples 3 and 4 :

Metronidazole was prepared using the same method as described in Examples 1 and 2, except that metronidazole (purchased from Hanil Pharm) was used instead of the active ingredient tinidazole used in Examples 1 and 2. Tongue cleaner and deodorant cleaner incorporating metronidazole and dexamethasone were prepared. The suspended particle diameter of the prepared detergent was approximately 1/20000 cm to 1/1000 cm.

Example 5 Sensory Test on Bad Breath Removal Effect

In order to examine the deodorizing effect of the detergents prepared in Examples 1, 2 and 3, the following organoleptic test was performed.

(1) Selection of patient to be examined and cleaning method

In consideration of gender and age among volunteer patients who suffer from bad breath, 14 patients were selected as the detergent subjects according to Examples 1, 2, and 3, respectively (total 42). After the morning meal and before bedtime wipe the tooth and the entire tongue bottom sincerely, 4 drops of each of the cleaning agents according to Examples 1, 2 and 3 of the present invention on a toothbrush, wipe the entire tongue evenly for 3 minutes and gently wash once with water It was made. The same procedure was repeated for 7 days before stopping. After the day he stopped, he brushed his whole tongue with a toothbrush moistened with regular toothpaste in the morning and evening after eating.

(2) Recognition Agent

Five men and women were selected as well-trained men and women (25 to 35 years old).

(2) Inspection method

Testers who stopped using the cleaners of Examples 1, 2 and 3 after 7 days were allowed to self-judge self-determination for bad breath for a period of about a month directly, and at the same time every day, As a result, the test results of bad breath were expressed by sensory indexes 0 to 3 as follows.

① oral cavity-Cover your mouth and nose and breathe in the covered hands and smell it.

② Tongue back front part-5 seconds after licking the back of the hand, smelled at a distance of about 3㎝.

③ Tongue Back-Scrape with a small disposable plastic spoon 5 seconds later smelled the spoon.

④ observed sensory index

0: No bad breath

1: I can not tell whether or not bad breath.

2: I have bad breath, but I am weak or intolerable.

3: Bad breath is too bad to endure.

The overall results for the cleaning agents of Examples 1, 2 and 3 are described in Tables 1 to 3, respectively.

Effect of Cleaning Agent of Example 1 Subject Self-Determination Sensory Index Sensory Indices Sensory Index Translate One 60 years old (male) 0 0 Bad breath for more than 30 days 2 Age 53 (M) 0 0 3 53 years old 0 0 4 48 years old 0 0 5 43 years old 0 0 6 38 years old 0 0 7 Age 31 (M) 0 0 8 55 years old 2 0 Effective for 30 days or more (presumed to be particularly sensitive to odors) 9 50 years old (male) 0 → 2 (after 2 days) 0 10 50 years old (male) 0 → 2 (after 2 days) 0 → 2 (3 days later) Poor cleaning 11 43 years old (male) 0 → 3 (3 days later) 0 → 3 (3 days later) Poor cleaning 12 42 years old 0 → 2 (after 7 days) 0 → 2 (after 8 days) Infection from others 13 Age 33 (M) 0 → 2 (after 10 days) 0 → 2 (after 10 days) Poor cleaning 14 28 years old (male) 0 → 3 (3 days later) 2 Suspicious of other diseases

Effect of Cleaning Agent of Example 2 Subject Self-Determination Sensory Index Sensory Indices Sensory Index Translate One 62 years old 0 0 Bad breath for more than 30 days 2 51 years old 0 0 3 Age 48 (M) 0 0 4 Age 46 (M) 0 0 5 Age 33 (M) 0 0 6 33 years old 0 0 7 28 years old (male) 0 0 8 28 years old 0 0 9 25 years old 0 0 10 Age 39 (M) 0 → 2 (after 7 days) 0 → 1 (after 7 days) Suspicion of Other Infection 11 Age 65 (M) 0 → 3 (after 6 hours) 0 → 2 (after 6 hours) Poor cleaning 12 50 years old 0 → 2 (after 12 days) 0 → 2 (after 15 days) Reinfection 13 Age 39 (M) 0 → 2 (after 20 days) 0 Effective for 30 days or more (presumed to be particularly sensitive to smells) 14 40 female 0 → 2 (after 2 days) 0 → 2 (3 days later) Poor cleaning

Effect of Cleaning Agent of Example 3 Subject Self-Determination Sensory Index Sensory Indices Sensory Index Translate One 72 years old 0 0 Bad breath for more than 30 days 2 Age 68 (M) 0 0 3 61 years old 0 0 4 55 years old 0 0 5 Age 54 (Female) 0 0 6 47 years old (male) 0 0 7 Age 42 (M) One 0 Get rid of bad breath for more than 30 days (presumed to be particularly sensitive to odors) 8 63 years old 2 0 9 63 years old (male) 0 → 2 (after 10 days) 0 10 Age 46 (M) 0 → 1 (after 7 days) 0 → 1 (after 7 days) Suspicion of Other Infection 11 38 years old 2 One Poor cleaning 12 38 years old 2 One Poor cleaning 13 35 years old 0 → 3 (after 7 days) 0 → 2 (after 9 days) Suspected reinfection 14 Age 29 (M) 0 → 2 (after 9 days) 0 → 2 (after 9 days) Suspected reinfection

As can be seen from the results of Tables 1 to 3, the results of Example 1 were used among 14 subjects according to each example. For the cleansers, 7 subjects were judged to have had a bad breath removal effect for more than 30 days, and the reviewers judged 9 subjects had a bad breath removal effect for more than 30 days; For the cleaning agent of Example 2, nine subjects judged that they had bad breath removal effect for 30 days or more, and the reviewers judged that 10 subjects had bad breath removal effects for 30 days or more; For the detergent of Example 3, six subjects judged themselves to have a bad breath removal effect for more than 30 days, and the identification agent judged that nine subjects had a bad breath removal effect for more than 30 days. If there is a difference between self-judgement and a judge's judgment, patients with bad breath, especially those who are sensitive to odors, may still have bad breath even after the bad breath is removed, or may not be able to tolerate a slight bad breath. It is interpreted as a case.

Therefore, it was confirmed that the detergent according to the present invention has a bad breath removal effect over a period of about a month or more by applying a short period of about a week. The remaining five to eight patients who failed treatment were presumed to have been poorly applied and inadequately applied to the cleaning agents of the present invention, or to have reinfected from others or from gastrointestinal reflux.

In addition, in the case of the detergent of the present invention in which the metronidazole and dexamethasone prepared in Example 4 were combined, the same test was conducted to confirm that 8 out of 14 subjects had a bad breath removal effect for 30 days or more.

The detergent for treating bad breath according to the present invention is simply buried in a toothbrush at home By brushing the tongue twice a day for 7 days, it has a good deodorizing effect for a long period of time over about a month due to short-term application. In addition, when applied as an external preparation for a short period of time with a suspension contained in a lean concentration, there was no side effect or myoclosis caused by the application.

Thus, the application of the tongue cleaner in accordance with the present invention will free many people from personal and social constraints and pain.

Claims (5)

A deodorant tongue cleaner comprising one compound selected from the group consisting of tinidazole and metronidazole as an active ingredient. The tongue cleaning agent of claim 1, further comprising dexamethasone. 3. The tongue cleaner of claim 2, wherein the compounding amount of tinidazole or metronidazole is 1.5% to 3.0% by weight of the total detergent and the amount of dexamethasone is 0.2% to 0.4% by weight of the total detergent. 4. The tongue cleaner of claim 3, wherein the compounding amount of tinidazole or metronidazole is 2.0% with respect to the total detergent weight and the compounding amount of dexamethasone is 0.2% with respect to the total detergent weight. The tongue cleaner according to any one of claims 1 to 4, which is in a suspended state or in a gel state.