Pharmaceutical composition

Abstract

To provide a pharmaceutical composition exhibiting superior effects in improving oral hygiene, in particular tongue coating and / or halitosis.SOLUTION: Incorporating menthol into a pharmaceutical composition containing Shokyo-shashin-to extract delivers a superior oral hygiene effect.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition for improving oral hygiene.

Background Art

[0002] In traditional Chinese medicine, based on the idea that the state of the tongue is an indicator of the state of the body, tongue diagnosis is performed in the prescription judgment of traditional Chinese medicine. In tongue diagnosis, the state of the entire tongue and the tongue coating on the surface of the tongue are observed. Also, since volatile sulfur compounds that cause bad breath are mainly produced from the tongue coating, reducing the tongue coating is also important for preventing bad breath.

[0003] As an example of the reported effects of traditional Chinese medicine on tongue coating and bad breath, Non-Patent Document 1 reports that taking the Pinellia and Magnolia Bark Decoction for 8 weeks tended to reduce volatile sulfur compounds, which are bad breath components, and tongue coating. Also, Non-Patent Document 2 lists the Coptis Detoxification Decoction, Coptis, etc., the Pinellia and Bupleurum Decoction, the Pinellia and Magnolia Bark Decoction, the Six Gentlemen Decoction, and the Modified Bupleurum and Peony Decoction as traditional Chinese medicines considered effective for bad breath diseases.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] The effects of traditional Chinese medicine are slow. When traditional Chinese medicine is prescribed for the treatment of a disease with tongue coating as one of the findings, even if the tongue coating findings can be improved as a result of the improvement of the disease, it cannot be said that the effects can be expected at a relatively early stage. In addition, although there are examples where traditional Chinese medicine is applied with a focus on oral hygiene, the improvement effects on tongue coating and / or bad breath have not been sufficiently studied.

[0006] Therefore, an object of the present invention is to provide a pharmaceutical composition having an excellent effect of improving oral hygiene, specifically tongue coating and / or bad breath.

Means for Solving the Problems

[0007] As a result of intensive studies, the present inventor unexpectedly found that by combining Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire with Menthol, the improvement effect on oral hygiene is enhanced. In addition, it has also been found that by combining Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire with Menthol, the unpleasant taste (specifically, a pungent taste) peculiar to Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire is reduced. The present invention has been completed by further studies based on these findings.

[0008] That is, the present invention provides an invention in the following aspects. Item 1. A pharmaceutical composition comprising Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire extract and Menthol. Item 2. The pharmaceutical composition according to Item 1, comprising 0.05 to 5 parts by weight of the Menthol per 100 parts by weight of the Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire extract. Item 3. The pharmaceutical composition according to Item 1 or 2, which is a tablet, pill, or capsule. Item 4. The pharmaceutical composition according to any one of Items 1 to 3, which is a plain tablet, powder, fine granule, granule, jelly, troche, or liquid preparation.

Effects of the Invention

[0009] According to the present invention, a pharmaceutical composition having an excellent effect of improving oral hygiene is provided.

Modes for Carrying Out the Invention

[0010] The pharmaceutical composition of the present disclosure is characterized by containing the extract of Shōkōrekishin-tō and menthol. Hereinafter, the pharmaceutical composition of the present disclosure will be described in detail. In this specification, a numerical range indicated by two numerical values and "~" shall include those two numerical values as the lower limit value and the upper limit value. For example, the notation of 2 to 15% by weight means 2% by weight or more and 15% by weight or less.

[0011] Ginger Xiexin Decoction extract As Shōkōrekishin-tō, a Kampō prescription described in "New Guide to General Kampō Prescriptions" (supervised by Yukihiro Goda and Takashi Hakozuka, edited by the Japan Kampō Raw Drug Preparation Association, published by Jihō Co., Ltd.) is preferable, and a mixed crude drug consisting of Pinelliae Rhizoma, Carotae Radix, Rhei Radix et Rhizoma, Glycyrrhizae Radix, Zingiberis Rhizoma Recens, Aurantii Fructus Immaturus, Magnoliae Officinalis Cortex, and Zingiberis Rhizoma (Alpiniae Officinarum Rhizoma is also acceptable) can be mentioned. In addition, Shōkōrekishin-tō includes the mixed crude drugs (Kampō prescriptions) described in currently popular Kampō-related correspondence as stipulated in the "Basic Handling Guidelines for Kampō Preparations" determined by the Kampō Raw Drug Research Society.

[0012] As the preferable component ratio of each crude drug constituting Shōkōrekishin-tō, 5 to 8 parts by weight of Pinelliae Rhizoma, 2.5 to 4 parts by weight of Carotae Radix, 2.5 to 4 parts by weight of Rhei Radix et Rhizoma, 2.5 to 4 parts by weight of Glycyrrhizae Radix, 2.5 to 4 parts by weight of Zingiberis Rhizoma Recens, 1 part by weight of Aurantii Fructus Immaturus, 1 to 2 parts by weight of Magnoliae Officinalis Cortex, and 0.5 to 2 parts by weight of Zingiberis Rhizoma (2 to 4 parts by weight when using Alpiniae Officinarum Rhizoma) can be mentioned.

[0013] The extract of Shōkōrekishin-tō may be obtained as an extract solution by subjecting the above-mentioned mixed crude drug to an extraction treatment and concentrating the obtained extract solution as necessary, or may be obtained as an extract powder by subjecting the extract solution to a drying treatment.

[0014] In the production of the extract of Shōkōrekishin-tō, although the extraction solvent used in the extraction treatment is not particularly limited, examples include water or aqueous ethanol, and preferably water. Also, the drying treatment is not particularly limited, and known methods such as spray drying method, or a method of adding an appropriate adsorbent (such as anhydrous silicic acid, starch, etc.) to a soft extract with an increased concentration of the extract solution to obtain an adsorbed powder can be mentioned.

[0015] In the pharmaceutical composition of the present disclosure, the content of the Sho-saiko-to extract (referring to the amount converted to the dry extract amount; the same applies hereinafter) is not particularly limited and may be appropriately set according to the efficacy to be exerted, etc. For example, 30 to 99% by weight can be mentioned. From the viewpoint of reducing the unpleasant taste (specifically, the astringent taste) peculiar to the Sho-saiko-to extract and obtaining an improved taste during administration, the content of the Sho-saiko-to extract in the pharmaceutical composition of the present invention is preferably 30 to 90% by weight, more preferably 30 to 80% by weight, still more preferably 30 to 70% by weight, and even more preferably 30 to 66% by weight. Further, since the unpleasant taste peculiar to the Sho-saiko-to extract is reduced in the pharmaceutical composition of the present invention, even when the Sho-saiko-to extract is contained in a relatively large amount, the unpleasant taste can be effectively reduced and an improved taste during administration can be obtained. From such a viewpoint, the preferred amount of the content of the Sho-saiko-to extract in the pharmaceutical composition of the present invention is preferably 40 to 99% by weight, more preferably 45 to 99% by weight, still more preferably 50 to 99% by weight, and particularly preferably 55 to 99% by weight or 60 to 99% by weight.

[0016] Note that the amount converted to the dry extract amount is the amount itself when using dry extract (extract powder), and when using an extract solution or soft extract, it is the amount converted to the remaining amount after removing the solvent. Further, when the dry extract powder contains additives such as adsorbents added during production, it is the amount excluding the additive.

[0017] Menthol As menthol, any of the d-form, l-form, and dl-form may be used. Among these menthols, preferably the l-form and dl-form can be mentioned, and more preferably the l-form can be mentioned. Further, as a blending material of menthol, an essential oil containing menthol may be used.

[0018] The content of menthol in the pharmaceutical composition of the present disclosure is not particularly limited and can be appropriately set according to the required degree of oral hygiene improvement effect and / or off-flavor reduction effect. For example, the content of menthol in the pharmaceutical composition of the present disclosure may be 0.05 to 5 parts by weight per 100 parts by weight of the content of the decoction of ginger and pinellia for purging the stomach-fire. Furthermore, from the perspective of further enhancing the oral hygiene improvement effect and / or from the perspective of further enhancing the off-flavor reduction effect of the specific off-flavor of the decoction of ginger and pinellia for purging the stomach-fire (specifically, the astringent taste) and the specific off-flavor of menthol (specifically, the bitter taste), it is preferably 0.1 to 4.5 parts by weight, more preferably 0.15 to 4 parts by weight, still more preferably 0.2 to 3 parts by weight, 0.2 to 2.5 parts by weight, 0.2 to 2 parts by weight, or 0.2 to 1 part by weight, and even more preferably 0.35 to 0.6 parts by weight.

[0019] The specific content of menthol in the pharmaceutical composition of the present disclosure is not particularly limited and can be appropriately set according to the required degree of oral hygiene improvement effect and / or off-flavor reduction effect. For example, the specific content of menthol in the pharmaceutical composition of the present disclosure may be 0.035 to 3.2% by weight. Furthermore, from the perspective of further enhancing the oral hygiene improvement effect and / or from the perspective of further enhancing the off-flavor reduction effect of the specific off-flavor of the decoction of ginger and pinellia for purging the stomach-fire (specifically, the astringent taste) and the specific off-flavor of menthol (specifically, the bitter taste), it is preferably 0.065 to 2.5% by weight, more preferably 0.1 to 2.5% by weight, still more preferably 0.13 to 1.9% by weight, 0.13 to 1.6% by weight, 0.13 to 1.3% by weight, or 0.13 to 0.6% by weight, and even more preferably 0.2 to 0.35% by weight.

[0020] Note that the content of menthol represents its own content when a purified product of menthol is used, and represents the amount of menthol contained in the essential oil blended when an essential oil containing menthol is used as a blending material for menthol.

[0021] Other active ingredients In addition to the extracts of Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire and menthol, the pharmaceutical composition of the present disclosure may or may not contain additives and / or bases according to the dosage form. Additives and bases, regardless of whether they are contained or not, are not particularly limited as long as they are pharmaceutically acceptable. For example, excipients, binders, disintegrants, lubricants, isotonic agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, gloss agents, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, ultraviolet light protectants, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents, etc. may be mentioned. These additives and bases may be used alone or in combination of two or more. Also, the content of these additives and bases is appropriately set according to the type of additives and bases used, the dosage form of the pharmaceutical composition, etc.

[0022] In addition to the extracts of Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire and menthol, the pharmaceutical composition of the present disclosure may or may not contain other pharmacological components. The types of pharmacological components, regardless of whether they are contained or not, are not particularly limited. For example, antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeine, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drugs, crude drug extract powders, vitamins, etc. may be mentioned. These pharmacological components may be used alone or in combination of two or more. Also, the content of these pharmacological components may be appropriately set from known ones according to the type of pharmacological components used, etc.

[0023] Dosage form Regarding the dosage form of the pharmaceutical composition of the present disclosure, there is no particular limitation as long as it can be orally administered, and it may be either a liquid preparation or a solid preparation. Specific examples of solid preparations include tablets (including coated tablets and uncoated tablets), pills, troches, capsules (including hard capsules and soft capsules), powders, fine granules, granules (including dry syrups).

[0024] The pharmaceutical composition of the present disclosure has an effect of improving oral hygiene such as improving tongue coating and / or bad breath by co-formulating menthol with the extract of Zingiberis Rhizoma Recens Decoction for Purging Stomach-Fire. Not only dosage forms that are easily touched directly by the tongue during administration, but also dosage forms that are difficult to touch directly by the tongue or not touched at all during administration can effectively obtain the effect of improving oral hygiene. From this perspective, suitable dosage forms of the pharmaceutical composition of the present disclosure include tablets, pills, and capsules.

[0025] The unpleasant tastes peculiar to the extract of Zingiberis Rhizoma Recens Decoction for Purging Stomach-Fire and menthol are remarkable enough to be clearly felt even in uncoated tablets, which are dosage forms that inherently tend to feel the taste of the preparation itself. The pharmaceutical composition of the present disclosure can reduce the unpleasant taste peculiar to the extract of Zingiberis Rhizoma Recens Decoction for Purging Stomach-Fire (specifically, astringent taste) and the unpleasant taste peculiar to menthol (specifically, bitter taste) by co-formulating menthol with the extract of Zingiberis Rhizoma Recens Decoction for Purging Stomach-Fire. Therefore, not only dosage forms that are difficult to feel the taste of the preparation itself during administration, but also dosage forms that are easy to feel the taste of the preparation itself can effectively obtain the effect of reducing unpleasant taste. From this perspective, suitable dosage forms of the pharmaceutical composition of the present disclosure include uncoated tablets, powders, fine granules, granules, jelly preparations, troches, and liquid preparations.

[0026] To prepare the pharmaceutical composition of the present disclosure into the above-mentioned dosage form, it may be formulated according to the usual formulation methods employed in the pharmaceutical field using the extract of Zingiberis Rhizoma Recens Decoction for Purging Stomach-Fire, menthol, and additives, bases, and / or pharmacological components added as necessary.

[0027] Use The pharmaceutical composition of the present disclosure can be used to improve oral malodor hygiene. Improvement of public hygiene includes at least one of improvement of tongue coating and improvement of oral malodor. Oral malodor includes at least one of the intensity of oral malodor and the unpleasantness of oral malodor.

[0028] The improvement effect of tongue coating can be confirmed by the decrease in the tongue coating index (TCI) based on the "Examination of Poor Oral Hygiene by Visual Inspection (Tongue Coating Index; TCI)" listed in the "Basic Concepts on Oral Function Decline (March 2018, Japanese Dental Association)".

[0029] The intensity of oral malodor can be confirmed by the decrease in the odor intensity score based on the "Six-stage Odor Intensity Display Method" listed in the "Odor Index Regulation Guidelines (March 2001, Environmental Management Bureau, Ministry of the Environment)".

[0030] The unpleasantness of oral malodor can be confirmed by the improvement of the pleasant-unpleasant score based on the "Nine-stage Pleasant-Unpleasant Display Method" set by the sensory test group in the survey on the setting of malodor standards commissioned by the Environmental Agency (Japanese Society for Environmental Hygiene, 1971).

[0031] Dosage and administration The pharmaceutical composition of the present disclosure is administered by oral administration. The dosage of the pharmaceutical composition of the present disclosure is appropriately set according to the target symptoms, age, etc. For example, as the daily intake, in terms of the dried extract amount conversion amount of the Zingiber and Pinellia Decoction for Purging Heart-Fire, it can be 1000 - 6000 mg or 1000 - 4000 mg, preferably 1500 - 3000 mg, more preferably 2000 - 2500 mg, and it can be taken in 2 - 3 divided doses per day.

[0032] There is no particular limitation on the timing of taking the pharmaceutical composition of the present disclosure, and it may be before meals, after meals, or between meals, but preferably before meals or between meals.

Examples

[0033] Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.

[0034] Preparation of Ginger Xiexin Decoction extract powder As raw crude drugs, 5 parts by weight of ginger (the same applies hereinafter), 2.5 parts by weight of carrot, 2.5 parts by weight of saffron, 2.5 parts by weight of licorice, 2.5 parts by weight of perilla, 1 part by weight of cinnamon, 1.5 parts by weight of kansui, and 0.5 part by weight of ginger were used. After chopping these, 15 times the weight of water was used for extraction at 95°C or higher for 60 minutes, followed by centrifugation to obtain an extract, which was concentrated under reduced pressure and dried using a freeze dryer to obtain a dried extract powder of the ginger xiexin decoction. Incidentally, the daily dosage of the obtained dried extract powder of the ginger xiexin decoction was set at 2250 mg.

[0035] Formulation of pharmaceutical composition Using the obtained dried extract powder of the ginger xiexin decoction and / or l-menthol and appropriate additives, pharmaceutical compositions (Comparative Examples 1 to 5 and Examples 1 to 8) having the compositions shown in Tables 3 to 5 were formulated.

[0036] Experimental method Among the subjects complaining of halitosis with visible tongue coating, the formulated pharmaceutical compositions were administered to them three times a day before meals for 5 days. The degree of tongue coating adhesion (TCI) before the start of administration and 5 days after administration, and the odor intensity and pleasantness / unpleasantness of the exhaled breath collected on an empty stomach before lunch were evaluated as follows.

[0037] <Evaluation method of TCI> Evaluation was based on the "Examination of Poor Oral Hygiene Status by Visual Inspection (Tongue Coating Index; TCI)". Specifically, the tongue surface was divided into 9 areas, and the degree of tongue coating adhesion in each area was evaluated in three levels (score 0: no tongue coating is observed, score 1: thin tongue coating where the lingual papillae are recognizable, score 2: thick tongue coating where the lingual papillae are not recognizable), and the total score was calculated. Based on the following formula, the tongue coating index (TCI) was derived. The value obtained by subtracting the TCI before the start of administration from the TCI 5 days after administration was derived as the "change amount". The smaller the value of the "change amount", the higher the evaluation of the tongue coating improvement effect. The results are shown in Tables 1 to 3.

[0038]

Chem.

[0039] <Method for Evaluating Odor Intensity and Pleasantness / Unpleasantness of Bad Breath before Lunch> The subject exhaled into an exhalation collection bag in one breath before lunch to fill the bag with exhaled air. After collecting the exhaled air, a person qualified as an odor judge evaluated the odor intensity (quantitative evaluation) and pleasantness / unpleasantness (qualitative evaluation) of the exhaled air in the bag.

[0040] The odor intensity of the exhaled air was evaluated on an 11-point scale with a score of 0 - 5 for odor intensity in 0.5-point increments based on the following "6-level odor intensity display method". The value obtained by subtracting the exhaled air intensity score before starting the administration from the exhaled air intensity score 5 days after administration was derived as the "change amount". The smaller the value of the "change amount", the higher the improvement effect on bad breath intensity can be evaluated. The results are shown in Tables 1 - 3.

Table 1

[0041] The unpleasantness of the exhaled air was evaluated on a 17-point scale with a score of +4 to -4 for pleasantness / unpleasantness in 0.5-point increments based on the following "9-level pleasantness / unpleasantness display method". The value obtained by subtracting the pleasantness / unpleasantness score before starting the administration from the pleasantness / unpleasantness score 5 days after administration was derived as the "change amount". The larger the value of the "change amount", the higher the improvement effect on the unpleasantness of bad breath can be evaluated. The results are shown in Tables 1 - 3.

Table 2

[0042] <Evaluation of Umami Reduction> After administration for 5 days, the subjects were asked to answer the evaluation results of the taste of the pharmaceutical composition according to the following 5 levels. The umami was comprehensively judged based on the umami specific to the extract of Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire (specifically, the astringent taste) and the umami specific to menthol (specifically, the bitter taste). When there was a difference in the levels of the astringent taste and the bitter taste, the level of the stronger umami was evaluated. The results are shown in Tables 1 - 3. 5: The off-flavor is very weak and it is easy to take. 4: The off-flavor is weak and it is somewhat easy to take. 3: It cannot be said either way. 2: Slightly feel the off-flavor and it is somewhat difficult to take. 1: Strongly feel the off-flavor and it is difficult to take.

[0043]

Table 3

[0044]

Table 4

[0045]

Table 5

[0046] As shown in Table 3, in the pharmaceutical composition of granules containing the extract of Zingiberis Rhizoma Recens Decoction for Purging Heart-Fire alone (Comparative Example 1), the effect of improving tongue coating was slight, and almost no effect of improving halitosis was observed. Also, in the pharmaceutical compositions of granules containing menthol alone (Comparative Examples 2 to 4), neither the effect of improving tongue coating nor the effect of improving halitosis was observed. On the other hand, as shown in Table 4, in the pharmaceutical compositions of granules containing the extract of Zingiberis Rhizoma Recens Decoction and menthol (Examples 1 to 5), remarkable and excellent effects of improving tongue coating and halitosis were obtained. Similarly, as shown in Table 5, in the pharmaceutical composition of tablets containing the extract of Zingiberis Rhizoma Recens Decoction alone (Comparative Example 5), the effect of improving tongue coating was slight and no effect of improving halitosis was observed, but in the pharmaceutical compositions of tablets containing the extract of Zingiberis Rhizoma Recens Decoction and menthol (Examples 6 to 8), remarkable and excellent effects of improving tongue coating and halitosis were obtained. In particular, in the pharmaceutical compositions containing the extract of Zingiberis Rhizoma Recens Decoction and menthol in a predetermined ratio (Examples 1 to 4, 6 to 8), more remarkable effects of improving tongue coating and halitosis were obtained.

[0047] Furthermore, in the pharmaceutical compositions containing the extract of Shōkyō-gishintō alone (Comparative Examples 1 and 5), the taste was astringent and the palatability was poor. In the pharmaceutical compositions containing menthol alone (Comparative Examples 2 to 4), the bitterness was strong and the palatability was poor. However, in the pharmaceutical compositions containing the extract of Shōkyō-gishintō and menthol (Examples 1 to 5, Examples 6 to 8), both the astringent taste and the bitterness were reduced, and the palatability was improved. In particular, in the pharmaceutical compositions containing the extract of Shōkyō-gishintō and menthol at a predetermined ratio (Examples 1 to 4, 6 to 8, especially Examples 1 to 3, 6 to 8), the astringent taste and the bitterness were significantly reduced, and a significant improvement effect on the palatability was obtained.

Claims

1. A pharmaceutical composition comprising a ginger xiexin decoction extract and menthol.

2. The pharmaceutical composition according to Claim 1, comprising 0.05 to 5 parts by weight of the menthol per 100 parts by weight of the ginger xiexin decoction extract.

3. The pharmaceutical composition according to Claim 1, which is a tablet, pill, or capsule.

4. The pharmaceutical composition according to Claim 1, which is a plain tablet, powder, fine granule, granule, jelly, troche, or liquid preparation.

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