JP2023010444A - Oral patch sheet - Google Patents

Abstract

To provide an oral patch sheet that effectively suppresses the induction of discomfort while containing an active ingredient that can cause excessive stimulation.SOLUTION: An oral patch sheet contains the following components (A), (B), and (C): (A) an oral cavity stimulating active ingredient; (B) 3-35 mass% of a sugar alcohol; and (C) a water soluble polymer. The dissolution amount of the oral patch sheet is 0.4-5.5 g/cm2 per unit area of the oral patch sheet per minute when the oral patch sheet is applied to the oral cavity.SELECTED DRAWING: None

Description

The present invention relates to an oral patch sheet.

The organs that make up the oral cavity, such as the teeth, gums, palate, and tongue, are moistened by the secreted saliva, and perform functions such as chewing and swallowing food, tasting food, and speaking. It is also an important organ involved in Therefore, if these organs become abnormal, it may cause various diseases and functional disorders such as eating, and it may also damage the aesthetic aspect. I can't

Teeth, which are one of the organs that make up the oral cavity, are known to cause unnecessary discoloration, gingival discoloration, periodontal disease, gingivitis, etc. It is In order to realize such proper care of teeth, it is necessary to consider that the site is always filled with saliva, and various adhesive sheets containing active ingredients that exhibit desired effects have been developed.

For example, in Patent Document 1, a dental patch sheet having a layer (A) and a layer (B) exhibiting different pH values when dissolved in water and containing phytic acid or the like in the latter layer is disclosed. By applying this to teeth, phytic acid and the like are caused to act efficiently while the pH environment on the tooth surface changes over time, and whitening effects on the teeth are exhibited. In addition, Patent Document 2 includes a bottom adhesive layer and a top protective layer that are directly attached to teeth and/or gums, and each layer has a difference in adhesiveness to teeth and/or gums and dissolution rate in saliva. A long-lasting film-like external preparation for periodontal disease is disclosed, and the external preparation as a whole has a dissolution rate that does not completely dissolve in saliva for at least 3 hours during sleep from the start of sleep, so that it can be kept in the oral cavity for a long time. I am trying to make it stay and to fully demonstrate the effect of the medicinal ingredients during sleep.
On the other hand, Patent Document 3 discloses an aroma film for palatal application containing a water-soluble polymer, a fragrance having a sedative or slimming effect, a polyhydric alcohol and/or a surfactant. It enhances the fragrance. In addition, Patent Document 4 discloses a film-like oral film containing hydroxypropyl cellulose with a specific viscosity, polyvinyl alcohol, sugar alcohol and/or polyhydric alcohol, and a specific amount of nonionic surfactant, and showing a specific blending ratio. Furthermore, Patent Document 5 discloses an intraoral patch containing a fragrance and carrageenan and pullulan in a specific mass ratio, both of which stably impart a refreshing feeling and aroma. We are trying to

WO2014/069595 JP 2016-84287 A JP 2007-99695 A JP 2014-172886 A JP 2006-182669 A

Such a sheet to be applied to a desired site in the oral cavity may give excessive sensory stimulation and taste stimulation not only to the site of application but also to the mucous membrane, gums, tongue, etc. existing in the vicinity, depending on the active ingredient blended. , may cause discomfort.
However, none of the techniques described in the above patent documents pays attention to solving such factors, and there is still room for improvement.

That is, the present invention relates to an oral patch sheet that effectively suppresses the induction of discomfort while containing an active ingredient that may cause excessive irritation.

Therefore, the present inventor conducted various studies and found that an oral patch containing a specific amount of a sugar alcohol and a water-soluble polymer together with an active ingredient that has the property of inducing irritation in the oral cavity, and controlling the elution amount of the oral patch. The inventors have found that an oral patch sheet can be obtained that can effectively suppress irritation derived from active ingredients.

Accordingly, the present invention provides the following components (A), (B), and (C):
(A) Oral cavity stimulating active ingredient (B) Sugar alcohol 3% by mass or more and 35% by mass or less (C) An oral patch sheet containing a water-soluble polymer,
When the oral patch sheet is applied to the oral cavity, the amount of dissolution of the oral patch sheet per unit area of the oral patch sheet per unit area is 0.4 mg/cm ² or more and 5.5 mg/cm ² or less per minute. This is to provide an oral patch sheet.

According to the oral patch sheet of the present invention, while containing an oral stimulating active ingredient that may cause excessive irritation, in order to appropriately control the solubility of the sheet after being applied to the oral cavity, such an active ingredient While fully enjoying the desired action of the adhesive, it is possible to effectively suppress excessive sensory stimulation and taste stimulation at the application site, etc., and to realize a comfortable feeling of use.
In addition, the oral patch sheet of the present invention has appropriate flexibility and conformability to the site where it is attached, is excellent in handleability during use, and can effectively prevent unnecessary breakage and breakage.

The present invention will be described in detail below.
Here, the site to which the oral patch sheet of the present invention is attached is the organ that constitutes the oral cavity. The bottom of the mouth, etc.
In addition, "intraoral irritation" means the property of stimulating the sensory organs in the oral cavity to bring about sensations and taste sensations. Furthermore, "sensory stimulus" means a stimulus perceived as a tingling or tingling sensation, and gustatory stimulus means a stimulus perceived as bitterness, pungency, or the like.

The oral patch sheet of the present invention contains an oral stimulating active ingredient as component (A). The active ingredient is generally used as an active ingredient or medicinal ingredient that can be applied to the oral cavity. It is a component that gives a tingling feeling inside or is perceived as an unpleasant taste such as excessive bitterness, pungent taste, or salty taste.

Examples of such component (A) include one or more selected from cooling component (a1), antiviral component (a2), and bactericidal component (a3).
Specific examples of cooling ingredients of component (a1) include menthol such as l-menthol and d-menthol, d-camphor, dl-camphor, d-borneol, dl-borneol, geraniol, and the like, and mucosal surfaces. 1 or 2 or more components selected from substances capable of stimulating thermoreceptors (cold sensation receptors such as TRPM8) to convey a cool sensation to the user.
Specifically, the antiviral component of component (a2) is selected from catechins, black tea polyphenols (theaflavin), ellagic acid, quercetin derivatives, gossypetin, phenethyl caffeate, casuarictin, butein, azidothymidine, zanamivir, oseltamivir, and the like. one or two or more components.
Specific examples of the bactericidal component of component (a3) include one or more selected from cationic bactericidal agents such as cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, isopropylmethylphenol, and triclosan. be done.

Although the content of component (A) may vary depending on the selected components, it is preferably 0.001% by mass or more in the total amount of the oral patch sheet of the present invention from the viewpoint of sufficiently bringing about the desired action. , more preferably 0.01% by mass or more. The content of component (A) is preferably 10% by mass or less in the total amount of the oral patch sheet of the present invention from the viewpoint of effectively suppressing excessive sensory stimulation and gustatory stimulation while enjoying the desired action. Yes, more preferably 7.5% by mass or less, still more preferably 5% by mass or less, and even more preferably 1% by mass or less.

Specifically, the content of the component (a1) is the total amount of the oral patch sheet of the present invention, from the viewpoint of effectively suppressing the tingling sensation that may be caused in the oral cavity while providing a good refreshing feeling. Among them, it is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, still more preferably 0.05% by mass or more, and still more preferably 0.1% by mass or more. , Still more preferably 0.2% by mass or more, still more preferably 0.3% by mass or more, still more preferably 0.4% by mass or more, preferably 5% by mass or less, and more It is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably 0.8% by mass or less.
The content of component (a2) is preferably 0.4% in the total amount of the oral patch sheet of the present invention, from the viewpoint of effectively inactivating viruses and effectively suppressing the bitterness that may be caused in the oral cavity. % by mass or more, more preferably 0.8% by mass or more, still more preferably 1.2% by mass or more, preferably 10% by mass or less, more preferably 8% by mass or less, and further It is preferably 7.5% by mass or less, more preferably 6% by mass or less, and even more preferably 5% by mass or less.
The content of the component (a3) is in the total amount of the oral patch sheet of the present invention from the viewpoint of effectively suppressing the bitterness and tingling sensation that may be caused in the oral cavity while exhibiting an excellent bactericidal effect. , preferably 0.001% by mass or more, more preferably 0.005% by mass or more, still more preferably 0.01% by mass or more, preferably 1% by mass or less, and more preferably 0.01% by mass or more. It is 5% by mass or less, more preferably 0.1% by mass or less, even more preferably 0.08% by mass or less, and even more preferably 0.05% by mass or less.

The oral patch sheet of the present invention contains 3% by mass or more and 35% by mass or less of sugar alcohol as the component (B). As a result, due to the synergistic effect with the component (C) described later, the solubility of the sheet after being applied in the oral cavity can be appropriately controlled, and the diffusion of the component (A) into the oral cavity can be controlled. To sufficiently bring about a desired action while effectively suppressing the expression of excessive sensory stimulation and taste stimulation in, etc. In addition, it is possible to impart appropriate flexibility along with good conformability to the application site, prevent unnecessary breakage and breakage, and ensure good handleability.

Component (B) specifically includes one or more selected from xylitol, sorbitol, erythritol, reduced palatinose, and mannitol. Among them, one or more selected from xylitol, sorbitol, and erythritol are more preferable from the viewpoint of contributing to control of the solubility of the sheet, and one or two selected from xylitol and erythritol are more preferable, Xylitol is more preferred.

From the viewpoint of appropriately controlling the solubility of component (A) in the oral cavity and effectively suppressing the induction of irritation in the oral cavity, the content of component (B) is , 3% by mass or more, preferably 4% by mass or more, more preferably 5% by mass or more, still more preferably 6% by mass or more, and even more preferably 10% by mass or more. In addition, the content of the component (B) in the total amount of the oral patch sheet of the present invention, from the viewpoint of ensuring good conformability to the application site and imparting appropriate flexibility to prevent damage and breakage , 35% by mass or less, preferably 30% by mass or less, more preferably 25% by mass or less, and even more preferably 20% by mass or less. The content of component (B) is 3% by mass or more and 35% by mass or less, preferably 4 to 30% by mass, more preferably 5 to 25% by mass, in the total amount of the oral patch sheet of the present invention. % by mass, more preferably 6 to 20% by mass, and even more preferably 10 to 20% by mass.

The oral patch sheet of the present invention contains a water-soluble polymer as component (C). As a result, along with the component (B), the solubility of the component (A) in the oral cavity is moderately controlled, and the component (A) is slowly released into the oral cavity, causing excessive sensory stimulation at the application site and the like. To sufficiently bring about a desired action while effectively suppressing the expression of taste stimulation. In addition, it is possible to impart appropriate flexibility that brings about good handleability as well as good followability to the application site.
In addition, the water-soluble polymer means a water-soluble polymer having a solubility in water at 25° C. of 0.1% by mass or more.

Specific examples of such component (C) include one or more selected from pullulan, hydroxyethylcellulose, guar gum, hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, and agar.
Above all, the solubility of the component (A) in the oral cavity is moderately controlled, the component (A) is gently released into the oral cavity, and excessive sensory stimulation and taste stimulation are effectively expressed at the application site. From the viewpoint of sufficiently bringing about the desired action while suppressing the effect, and from the viewpoint of exhibiting good solubility in water such as saliva, pullulan, hydroxyethyl cellulose, guar gum, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, gelatin, and One or two or more selected from agar are preferable, and one or two or more selected from pullulan, hydroxypropylmethylcellulose, and gelatin are more preferable.

The content of the component (C) is determined from the viewpoint of appropriately controlling the solubility of the component (A) in the oral cavity, and from the viewpoint of imparting an appropriate degree of flexibility that brings about good followability and handleability to the application site. , preferably 17% by mass or more, more preferably 30% by mass or more, still more preferably 45% by mass or more, preferably 65% by mass or less, in the total amount of the oral patch sheet of the present invention, It is more preferably 60% by mass or less, still more preferably 55% by mass or less.

The mass ratio of the content of component (C) to the content of component (B) ((C)/(B)) is from the viewpoint of appropriately controlling the solubility of component (A) in the oral cavity, and From the viewpoint of imparting moderate flexibility that brings about good conformability to the site and handleability, it is preferably 0.45 or more, more preferably 1.2 or more, and still more preferably 2.25 or more. , preferably 22 or less, more preferably 12 or less, still more preferably 10 or less.

The oral patch sheet of the present invention desirably contains water (D). This can contribute to imparting good followability and handleability to the application site, and moderately controls the solubility of the component (A) in the oral cavity through the intervention of moisture such as saliva after application. be able to.
The content of component (D) is preferably 3% by mass or more, more preferably 6% by mass or more, still more preferably 9% by mass or more, in the total amount of the oral patch sheet of the present invention. is 20% by mass or less, more preferably 15% by mass or less, and still more preferably 10% by mass or less.
The content of water in the total amount of the oral patch sheet is the total amount of water contained in the total amount of the oral patch sheet (100% by mass). means the value obtained.

The mass ratio of the content of component (B) to the content of component (D) ((B)/(D)) is from the viewpoint of suppressing the expression of excessive sensory stimulation and taste stimulation at the application site, and the oral cavity. From the viewpoint of moderately controlling the solubility of component (A) in the or less, more preferably 2.9 or less, and still more preferably 2.5 or less.

The mass ratio of the content of component (C) to the content of component (D) ((C)/(D)) is from the viewpoint of imparting good followability and handleability to the application site, and to the oral cavity. is preferably 0.85 or more, more preferably 2 or more, still more preferably 4.5 or more, preferably 22 or less, from the viewpoint of appropriately controlling the solubility of the component (A) of It is more preferably 10 or less, still more preferably 6.5 or less.

The oral patch sheet of the present invention further contains a nonionic surfactant from the viewpoint of increasing the dispersibility and diffusibility of each component contained and appropriately controlling the solubility of component (A) in the oral cavity. is preferred. Examples of such nonionic surfactants include polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene copolymer, sucrose fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene Ethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene glycol fatty acid ester, polyoxyethylene phytosterol and phytostanol, polyoxyethylene lanolin and lanolin alcohol, polyoxyethylene alkylamine and fatty acid amide , polyoxyethylene alkylphenyl formaldehyde condensates, polyoxyethylene polyoxypropylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene alkylphenyl ethers, fatty acid ethanolamides, and the like.
Among them, polyoxyethylene hydrogenated castor oil, polyglycerol fatty acid ester, sho One or two selected from sugar fatty acid esters and polyoxyethylene sorbitan fatty acid esters is preferable, and it is more preferable to contain any one of polyoxyethylene hydrogenated castor oil and polyglycerin fatty acid ester, polyoxyethylene hydrogenated castor oil It is more preferable to contain

From the viewpoint of appropriately controlling the solubility of the component (A) in the oral cavity, the content of such a nonionic surfactant is preferably 0.5 to 10% by mass in the total amount of the oral patch sheet of the present invention. Yes, more preferably 1 to 5% by mass, still more preferably 2 to 3% by mass.

The oral patch sheet of the present invention preferably further contains a polyhydric alcohol from the viewpoint of enhancing the wettability of the sheet and enhancing the dispersibility and diffusibility of each contained component. As such a polyhydric alcohol, a low molecular weight polyhydric alcohol having a molecular weight of 200 or less is preferable. Specifically, glycerin such as glycerin, diglycerin and polyglycerin and polymers thereof; glycols such as ethylene glycol, propylene glycol and butylene glycol; ; and dialkylene glycols such as diethylene glycol and dipropylene glycol. Among them, it more preferably contains any one of glycerin, propylene glycol, butylene glycol, and dipropylene glycol, and more preferably contains glycerin and propylene glycol.

The content of such a polyhydric alcohol is preferably 50% by mass or less in the total amount of the oral patch sheet of the present invention, from the viewpoint of enhancing the wettability of the sheet and enhancing the dispersibility and diffusibility of each component contained. Yes, more preferably 40 to 0.1% by mass, still more preferably 30 to 3% by mass, still more preferably 20 to 5% by mass.

In addition to the components described above, the oral patch sheet of the present invention contains, insofar as the effects of the present invention are not impaired, for example, active ingredients other than the component (A); surfactants other than the nonionic surfactants; and pH adjusters. colorants; preservatives and the like.

The layer structure of the patch sheet for oral cavity of the present invention only needs to have a surface to be attached to the oral cavity, and may be a single layer. It may be a multi-layer sheet comprising an adhesive layer and a protective layer including a surface opposite to the surface to be adhered to the oral cavity. This can further improve the handleability of the oral patch sheet of the present invention.
Incidentally, whether the oral patch sheet of the present invention is a single-layered sheet or a multi-layered sheet, the amount of each component mentioned above means the amount in the total amount of the oral patch sheet.

Such protective layers include ethylcellulose, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate, hypromellose phthalate, shellac, polyvinyl acetate, polymethyl methacrylate, methacryloylethyl betaine/methacrylate copolymer, methacrylic acid copolymer, amino From the viewpoint of a protective layer, it is preferable to contain one or more water-insoluble polymers selected from alkyl methacrylate copolymers and agar. Among them, the protective layer is selected from ethyl cellulose and shellac from the viewpoint of suppressing excessive sensory stimulation and taste stimulation at the application site while ensuring good flexibility of the oral patch sheet of the present invention. It preferably contains one or two or more water-insoluble polymers.

The adhesive sheet for oral cavity of the present invention may further include an intermediate layer between the adhesive layer and the protective layer in addition to the adhesive layer and the protective layer. Desired components contained in the intermediate layer include those similar to component (A) described above, and may contain an active component different from component (A) contained in the adhesive layer.
Such an intermediate layer may be formed using the same water-soluble polymer as the adhesive layer.

In the oral patch sheet of the present invention, when the oral patch sheet is applied to the oral cavity, the amount of dissolution of the oral patch sheet per unit area of the oral patch sheet is 0.4 mg/cm per minute. ² or more and 5.5 mg/cm ² or less. Since the amount of dissolution of the oral patch sheet of the present invention is within such a range, the oral patch sheet of the present invention slowly releases the component (A) into the oral cavity, While effectively suppressing the expression of excessive sensory stimulation and gustatory stimulation in, etc., it is possible to sufficiently bring about the desired action.

When the oral patch sheet of the present invention is applied to the oral cavity, the amount of dissolution of the oral patch sheet per unit area of the oral patch sheet per minute is 0.4 mg/cm ² or more, It is preferably 0.45 mg/cm ² or more, more preferably 0.5 mg/cm ² or more, still more preferably 0.55 mg/cm ² or more, and even more preferably 0.6 mg/cm ² or more. , more preferably 0.65 mg/cm ² or more, 5.5 mg/cm ² or less, preferably 4 mg/cm ² or less, more preferably 3 mg/cm ² or less, and further It is preferably 2 mg/cm ² or less.
The amount of dissolution of such an oral patch sheet is the time until the sheet dissolution part completely dissolves when a 2 cm square sheet is attached to an acrylic plate and then immersed in water (25 ° C.) (hereinafter, "completely Also referred to as "dissolution time"), and from the weight (mg) of the oral patch sheet, the elution amount (mg) of the oral patch sheet eluted from a unit area (cm ² ) per minute is calculated. This is the desired value.

The thickness of the oral patch sheet of the present invention appropriately controls the elution amount of the component (A) after being applied to the oral cavity, and effectively suppresses excessive sensory stimulation and gustatory stimulation at the application site. From the viewpoint, it is preferably 20 μm or more, more preferably 40 μm or more, still more preferably 50 μm or more, still more preferably 60 μm or more, preferably 500 μm or less, more preferably 300 μm or less, It is more preferably 100 μm or less, and even more preferably 70 μm or less.
The thickness of the oral patch sheet means the average value (μm) of the thickness measured at three arbitrary points on the sheet using a micrometer.

The strain of the oral patch sheet of the present invention at a tensile stress of 20 MPa is preferably 2% or more from the viewpoint of preventing damage or breakage during operation while ensuring good followability and flexibility at the application site. more preferably 3% or more, still more preferably 4% or more, preferably 12% or less, and more preferably 11% or less.
The strain at 20 MPa tensile stress of the oral patch sheet is obtained by setting the sheet to be measured in a jig for strain measurement using a rheometer, and changing the shear stress from 1 to 2 × 10 ⁷ Pa. It is a value obtained by measuring the strain when the strain is applied and converting the strain at a shear stress of 20 MPa into the amount of change (%) from the initial length.

In the oral patch sheet of the present invention, a release sheet may be further laminated on the side of the sheet that is to be stuck in the oral cavity. By laminating such a release sheet, when using the oral patch sheet of the present invention, the release sheet can be peeled off to expose the surface to be attached to the oral cavity, and hygiene and operability can be improved.
Such a release sheet is made of one or more selected from polyethylene terephthalate (PET), polypropylene (PP), polyethylene (PE), and mixtures thereof, from the viewpoint of good release. is preferred, and it is more preferred that it is made of polyethylene terephthalate.

The shape of the oral patch sheet of the present invention depends on the shape of the site selected from the tooth to be attached, the organ located around the tooth including the gingiva (peripheral part of the tooth), the palate, the tongue, the floor of the mouth, and the like. , may be appropriately determined in consideration of the operability at the time of use.

EXAMPLES The present invention will be specifically described below based on examples. In addition, unless otherwise indicated in the table, the content of each component indicates % by mass.
Each physical property of the sheet was measured by the following methods.

<<Total water content of oral patch sheet (D)>>
Using an automatic moisture measuring device (AQV-300 series, manufactured by Hiranuma Co., Ltd.), the total moisture content of the oral patch sheet was measured.

<<Distortion at 20 MPa tensile stress of oral patch>>
Using a rheometer (MCR502, manufactured by Anton Paar), the sheet to be measured was set in a jig for strain measurement, and the strain was measured when the shear stress was changed from 1 to 2×10 ⁷ Pa, The strain at a shear stress of 20 MPa was converted to the amount of change (%) from the initial length and obtained.

<<Measurement of the dissolution amount (mg/cm ² ) of the sheet after every 1 minute when applied to the oral cavity>>
A 2 cm square test piece sheet was cut out from each sheet, attached to an acrylic plate, and then immersed in water to measure the time required for the dissolution part of the sheet to completely dissolve (complete dissolution time). Next, it was obtained by calculating the eluted amount (mg) of the sheet eluted from a unit area (cm ² ) per minute from the weight (mg) of the sheet.
Three or more test specimen sheets were used for such measurements, and any three test specimen sheets whose measured complete dissolution times fell within an error range of 30 seconds or less were extracted, and the average value was obtained as the complete dissolution time. .

To check whether the sheet has completely dissolved or not, when the acrylic sheet is removed from the water and touched to the area where the sheet is attached, you will feel the same amount of friction as the surface of the acrylic sheet without feeling stickiness due to the dissolution residue of the sheet. Judged by whether it is possible or not. In addition, by removing the acrylic sheet from the water and drying it, we can confirm whether the sheet has completely dissolved by comparing the frictional force between the area where the sheet is attached and the surface of the acrylic sheet outside the area where the sheet is attached. can do.
Furthermore, as a method for measuring the time until the sheet completely dissolves, after attaching a 2 cm square test piece sheet to an acrylic plate and immersing it in water, the component (A) eluted from the sheet into water over time. It is also possible to measure the elution amount of the sheet, and take the time until the elution amount stagnates (reaches a plateau) as the dissolution time of the sheet.
In order to measure the elution amount of component (A), an appropriate analytical method may be used according to each component. Examples of each analysis method when component (A) is catechin and l-menthol are shown below.

[Analysis method of catechin]
Catechin analysis methods include, for example, high performance liquid chromatography-mass spectrometry. The sample solution is filtered through a filter (0.45 μm) and subjected to high performance liquid chromatography.
<High performance liquid chromatograph operating conditions>
Model: SCL-10AVP, Shimadzu Corporation Detector: UV detector wavelength 280 nm
Column: Octadecyl group-introduced packed column for liquid chromatography, L-Column TM ODS, 4.6 mmφ×250 mm, Chemicals Evaluation and Research Institute Column temperature: 35°C
Mobile phase A: distilled aqueous solution containing 0.1 mol/L of acetic acid (liquid A)
Mobile phase B: Acetonitrile solution containing 0.1 mol/L of acetic acid (B solution)
Flow rate: 1 mL/min Sample injection volume: 10 μL
The gradient conditions are as follows.
Concentration gradient conditions (volume %)
Time Liquid A concentration Liquid B concentration
0 minutes 97% 3%
5 minutes 97% 3%
37 minutes 80% 20%
43 minutes 80% 20%
43.5 minutes 0% 100%
48.5 minutes 0% 100%
49 minutes 97% 3%
60 minutes 97% 3%

[Analysis method of l-menthol]
Analysis methods for l-menthol include, for example, gas chromatography-mass spectrometry. Specifically, for example, 150 mL of water and 8 mL of heptane are added to 2.0 g of a sample, distilled with a distillation apparatus for quantitative determination of essential oils, and the heptane layer is fractionated and used as a measurement sample, and the instrument conditions are as follows. can be set and measured.
<Gas chromatograph operating conditions>
Model: 6890N/5975B interXL (Agilent Technologies)
Column: DB-WAX (Agilent Technologies)
Temperature: Sample inlet 220°C, column 80°C (held for 1 minute) → 5°C/minute temperature increase → 150°C → 15°C/minute temperature increase → 200°C
Injection method: split 30:1
Injection volume: 1 μL
Gas flow rate: Helium 1 mL/min Ion source temperature: 230°C
Ionization method: EI
Set mass number: m / z 136 naphthalene-d8 (internal standard substance)

[Examples 1 to 6, Comparative Examples 1 to 4]
According to the formulation shown in Table 1, while appropriately adjusting the amount of water while considering the solid content, each component is mixed to prepare a stock solution, and the obtained stock solution is coated on a release sheet and dried. Each patch sheet for oral cavity was produced.
Using the oral patch sheet thus obtained, each evaluation was performed according to the following methods.
The obtained oral patch sheet had a thickness of 65±5 μm and a strain of 8±5% at a tensile stress of 20 MPa.
Table 1 shows the results.

<<Presence or absence of intraoral irritation and evaluation of sheet handleability>>
The obtained patch sheet for oral cavity was cut into a size of about 4 x 5 cm so that the total amount was 0.2 g, and when this was attached on the tongue and completely dissolved, the oral cavity stimulation (cooling sensation, The presence or absence of bitterness) and the handleability of the sheet were evaluated according to the evaluation criteria shown below.

・Presence or absence of intraoral irritation 1: Very strong irritation 2: Strong irritation 3: Slight irritation to the extent that there is no problem 4: Almost no irritation 5: No irritation at all

・Handling of sheet A: Moderate flexibility and excellent handleability B: Handleability with almost no problem C: Too soft or too hard to handle

Claims (6)

The following components (A), (B), and (C):
(A) Oral cavity stimulating active ingredient (B) Sugar alcohol 3% by mass or more and 35% by mass or less (C) An oral patch sheet containing a water-soluble polymer,
When the oral patch sheet is applied to the oral cavity, the amount of dissolution of the oral patch sheet per unit area of the oral patch sheet per unit area is 0.4 mg/cm ² or more and 5.5 mg/cm ² or less per minute. oral patch sheet. The oral patch sheet according to claim 1, wherein the content of water (D) is 3% by mass or more and 20% by mass or less. 3. The oral patch sheet according to claim 1 or 2, wherein the mass ratio ((C)/(B)) of the content of component (C) to the content of component (B) is 0.45 or more and 22 or less. . The oral patch sheet according to any one of claims 1 to 3, wherein the content of component (C) is 17% by mass or more and 65% by mass or less. The mass ratio ((B)/(D)) of the content of component (B) to the content of component (D) is 0.1 or more and 10 or less, according to any one of claims 1 to 4. oral patch sheet. The mass ratio ((C)/(D)) of the content of component (C) to the content of component (D) is 0.85 or more and 22 or less, according to any one of claims 1 to 5. oral patch sheet.