JP2023147255A - mouthwash - Google Patents
mouthwash Download PDFInfo
- Publication number
- JP2023147255A JP2023147255A JP2023048809A JP2023048809A JP2023147255A JP 2023147255 A JP2023147255 A JP 2023147255A JP 2023048809 A JP2023048809 A JP 2023048809A JP 2023048809 A JP2023048809 A JP 2023048809A JP 2023147255 A JP2023147255 A JP 2023147255A
- Authority
- JP
- Japan
- Prior art keywords
- gargle
- hydrogenated castor
- polyoxyethylene hydrogenated
- castor oil
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002324 mouth wash Substances 0.000 title claims abstract description 11
- 229940051866 mouthwash Drugs 0.000 title claims abstract description 9
- -1 fatty acid ester Chemical class 0.000 claims abstract description 115
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- 239000004359 castor oil Substances 0.000 claims abstract description 64
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 239000000796 flavoring agent Substances 0.000 claims abstract description 40
- 229960004830 cetylpyridinium Drugs 0.000 claims abstract description 35
- NEUSVAOJNUQRTM-UHFFFAOYSA-N cetylpyridinium Chemical compound CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NEUSVAOJNUQRTM-UHFFFAOYSA-N 0.000 claims abstract description 35
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 34
- 239000000194 fatty acid Substances 0.000 claims abstract description 34
- 229930195729 fatty acid Natural products 0.000 claims abstract description 34
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 30
- KKEMWYNNTBRYMR-UHFFFAOYSA-N azulene-1-sulfonic acid Chemical compound C1=CC=CC=C2C(S(=O)(=O)O)=CC=C21 KKEMWYNNTBRYMR-UHFFFAOYSA-N 0.000 claims abstract description 25
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 claims abstract description 23
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims abstract description 21
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 21
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- 239000000203 mixture Substances 0.000 claims abstract description 14
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
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- NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 4
- 150000004677 hydrates Chemical class 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
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- 235000003599 food sweetener Nutrition 0.000 description 3
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- 239000001685 glycyrrhizic acid Substances 0.000 description 3
- 229960004949 glycyrrhizic acid Drugs 0.000 description 3
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 3
- 235000019410 glycyrrhizin Nutrition 0.000 description 3
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 3
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 229920002884 Laureth 4 Polymers 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
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- 239000011780 sodium chloride Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- VIZXMHCBZLGUET-UHFFFAOYSA-N sodium gualenate Chemical compound CC(C)C1=CC=C(C)C2=C(S(O)(=O)=O)C=C(C)C2=C1 VIZXMHCBZLGUET-UHFFFAOYSA-N 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Abstract
Description
本発明はアズレンスルホン酸及び／又はその塩を含むうがい薬（含嗽剤）に関する。 The present invention relates to a gargle containing azulene sulfonic acid and/or a salt thereof.
アズレンスルホン酸及びその塩は、従来より抗炎症剤として汎用され、これを希釈させた水溶液でうがいをすることにより、扁桃炎、咽頭炎、口内炎、歯肉炎を鎮める効果が知られている。 Azulene sulfonic acid and its salts have been widely used as anti-inflammatory agents, and gargling with a diluted aqueous solution is known to be effective in soothing tonsillitis, pharyngitis, stomatitis, and gingivitis.
うがい薬には、のどのはれを抑えるアズレンスルホン酸及び／又はその塩等の抗炎症剤、口中やのどの粘膜で細菌の増殖を抑えるセチルピリジニウム及び／又はその塩等の殺菌剤、そして口中に清涼感を与え、口臭除去の効果を有するｌ－メントール等のテルペン類が配合されることが多い。
これらのうち、アズレンスルホン酸及び／又はその塩とセチルピリジニウム及び／又はその塩を同時に配合すると使用時の泡立ちが大きく、アズレンスルホン酸及び／又はその塩とｌ－メントール等のテルペン類を同時に配合するとこれら一方又は双方の結晶が析出し、さらに、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩とｌ－メントール等のテルペン類を同時に配合すると使用時に液垂れし、しかも使用感（含嗽時の風味）が悪いことが問題であった。
Gargles include anti-inflammatory agents such as azulene sulfonic acid and/or its salts, which suppress swelling of the throat, antibacterial agents such as cetylpyridinium and/or its salts, which suppress the growth of bacteria in the mucous membranes of the mouth and throat, and mouthwashes. Terpenes such as l-menthol are often added, which give a refreshing feeling and have the effect of removing bad breath.
Among these, when azulene sulfonic acid and/or its salt and cetylpyridinium and/or its salt are combined at the same time, foaming becomes large during use, and azulene sulfonic acid and/or its salt and terpenes such as l-menthol are combined at the same time. Then, crystals of one or both of these precipitate, and furthermore, if azulene sulfonic acid and/or its salt, cetylpyridinium and/or its salt, and terpenes such as l-menthol are mixed at the same time, the liquid will drip when used, and it will not feel good after use. The problem was that the flavor was bad when gargling.
前記の泡立ちについて、抗炎症作用が知られているグリチルリチン酸又はその塩を、発泡抑制剤としてうがい薬に配合した提案がなされている（特許文献１）。前記提案では、グリチルリチン酸又はその塩が矯味剤や甘味剤として医薬品に添加される旨の記載があるが、うがい薬の使用感（風味）を改善する程の十分な矯味性がグリチルリチン酸又はその塩にあるとは言い難い。 Regarding the above-mentioned foaming, a proposal has been made in which glycyrrhizic acid or its salt, which is known to have an anti-inflammatory effect, is added to a gargle as a foaming suppressant (Patent Document 1). The above proposal states that glycyrrhizic acid or its salts are added to pharmaceuticals as flavoring agents or sweeteners, but glycyrrhizic acid or its salts do not have sufficient taste-masking properties to improve the usability (flavor) of gargles. It's hard to say that it's in the salt.
本発明は、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩、そしてｌ－メントール等を含有するうがい薬において、使用時の泡立ち、結晶析出、そして使用時の液垂れを抑制し、含嗽時の風味にも優れるうがい薬を提供する。 The present invention suppresses foaming, crystal precipitation, and dripping during use in a gargle containing azulene sulfonic acid and/or its salt, cetylpyridinium and/or its salt, l-menthol, etc. To provide a gargle with excellent flavor when gargling.
すなわち本発明は、以下の［１］～［４］を対象とする。
［１］
アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩、及びｌ－メントールを含有する液体組成物において、下記（Ａ）、（Ｂ）、（Ｃ）及び（Ｄ）の各成分が配合されていることを特徴とするうがい薬。
（Ａ）サッカリンナトリウム及びアセスルファムカリウムから選択される１種以上の矯味剤、
（Ｂ）多価アルコール脂肪酸エステル、
（Ｃ）セルロース類、
（Ｄ）ポリオキシエチレン硬化ヒマシ油類。
［２］
前記（Ｂ）多価アルコール脂肪酸エステルが、グリセリン脂肪酸エステルであることを特徴とする、［１］に記載のうがい薬。
［３］
前記（Ｃ）セルロース類が、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース及びヒプロメロースからなる群から選択される１種以上であることを特徴とする、［１］に記載のうがい薬。
［４］
前記（Ｄ）ポリオキシエチレン硬化ヒマシ油類が、ポリオキシエチレン硬化ヒマシ油５、ポリオキシエチレン硬化ヒマシ油１０、ポリオキシエチレン硬化ヒマシ油２０、ポリオキシエチレン硬化ヒマシ油４０、ポリオキシエチレン硬化ヒマシ油５０、ポリオキシエチレン硬化ヒマシ油６０及びポリオキシエチレン硬化ヒマシ油１００からなる群から選択される１種以上であることを特徴とする、［１］乃至［３］のうちいずれか一項に記載のうがい薬。
That is, the present invention is directed to the following [1] to [4].
[1]
In a liquid composition containing azulene sulfonic acid and/or its salt, cetylpyridinium and/or its salt, and l-menthol, the following components (A), (B), (C), and (D) are blended. A mouthwash characterized by:
(A) one or more flavoring agents selected from saccharin sodium and acesulfame potassium;
(B) polyhydric alcohol fatty acid ester,
(C) cellulose,
(D) Polyoxyethylene hydrogenated castor oils.
[2]
The gargle according to [1], wherein the polyhydric alcohol fatty acid ester (B) is a glycerin fatty acid ester.
[3]
The gargle according to [1], wherein the cellulose (C) is one or more selected from the group consisting of hydroxyethylcellulose, hydroxypropylcellulose, and hypromellose.
[4]
The (D) polyoxyethylene hydrogenated castor oils include polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil Any one of [1] to [3], characterized in that it is one or more selected from the group consisting of oil 50, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene hydrogenated castor oil 100. Mouthwash listed.
本発明によれば、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩及びｌ－メントールを含有するうがい薬（液体組成物）において、うがい薬使用時の泡立ちや液垂れを抑制し、またアズレンスルホン酸及び／又はその塩やｌ－メントールの結晶析出を抑制するとともに、口に含んだ際には苦味等の不快な風味が抑制されてなる、うがい薬を提供することができる。 According to the present invention, a gargle (liquid composition) containing azulene sulfonic acid and/or its salt, cetylpyridinium and/or its salt, and l-menthol suppresses foaming and dripping during use of the gargle. Furthermore, it is possible to provide a gargle that suppresses crystal precipitation of azulene sulfonic acid and/or its salt and l-menthol, and suppresses unpleasant flavors such as bitterness when taken in the mouth.
［うがい薬］
本発明にうがい薬は、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩及びｌ－メントールを含有する液体組成物において、さらに、（Ａ）特定の矯味剤、（Ｂ）多価アルコール脂肪酸エステル、（Ｃ）セルロース類、及び（Ｄ）ポリオキシエチレン硬化ヒマシ油類の各成分が配合されてなることを特徴とする。
[Gargle medicine]
The gargle of the present invention is a liquid composition containing azulene sulfonic acid and/or its salt, cetylpyridinium and/or its salt, and l-menthol, and further contains (A) a specific flavoring agent, (B) a polyvalent It is characterized by containing the following components: alcohol fatty acid ester, (C) cellulose, and (D) polyoxyethylene hydrogenated castor oil.
〈アズレンスルホン酸及び／又はその塩〉
前記アズレンスルホン酸の塩とは、１，４－ジメチル－７－イソプロピルアズレン－３－スルホン酸の薬理学上許容される塩及びその水和物を指す。
前記アズレンスルホン酸及び／又はその塩は、抗炎症作用、抗アレルギー作用、肉芽新生及び上皮形成促進作用を有することが知られている。
薬理学上許容される塩としては、ナトリウム塩、カリウム塩、アンモニウム塩等が挙げることができ、中でもナトリウム塩（通常、アズレンスルホン酸ナトリウムと称する）を挙げることができる。
<Azulene sulfonic acid and/or its salt>
The salt of azulene sulfonic acid refers to a pharmacologically acceptable salt of 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid and a hydrate thereof.
The azulene sulfonic acid and/or its salts are known to have anti-inflammatory, anti-allergic, granulation and epithelial formation promoting effects.
Examples of pharmacologically acceptable salts include sodium salts, potassium salts, and ammonium salts, among which sodium salts (usually referred to as sodium azulene sulfonate) can be mentioned.
〈セチルピリジニウム及び／又はその塩〉
前記セチルピリジニウム及び／又はその塩とは、例えば、セチルピリジニウム塩酸塩が挙げられ、すなわち、１－ヘキサデシルピリジニウムクロリド及びその水和物を挙げることができる。本成分は、殺菌作用を有し、粘膜において細菌の増殖を抑え、のどの炎症を緩和し、歯周病や口臭を予防する効果が知られている。
<Cetylpyridinium and/or its salt>
Examples of the cetylpyridinium and/or its salts include cetylpyridinium hydrochloride, that is, 1-hexadecylpyridinium chloride and hydrates thereof. This ingredient has a bactericidal effect and is known to suppress the growth of bacteria in the mucous membranes, relieve throat inflammation, and prevent periodontal disease and bad breath.
〈ｌ－メントール〉
ｌ－メントールは、前述の通り口中に清涼感を与え、口臭除去の効果を有するとともに、一般に経口薬剤の風味を矯正し摂取しやすくする矯味剤としての役割をも担うものである。
<l-menthol>
As mentioned above, l-menthol has the effect of giving a refreshing feeling to the mouth and removing bad breath, and also generally plays the role of a flavoring agent that corrects the flavor of oral drugs and makes them easier to ingest.
（Ａ）特定の矯味剤
本発明のうがい薬は、（Ａ）矯味剤として、サッカリンナトリウム及びアセスルファム
カリウムから選択される少なくとも一種を含む。
前記サッカリンナトリウム及びアセスルファムカリウムは非糖質性合成甘味料として知られており、本発明のうがい薬では甘味料且つ矯味剤としての役割を担うとともに、後述する（Ｂ）多価アルコール脂肪酸エステルと（Ｃ）セルロース類と組み合わせて使用することで、うがい薬使用時の泡立ちを抑制する役割をも担うことができる。
(A) Specific Flavoring Agent The gargle of the present invention contains at least one selected from saccharin sodium and acesulfame potassium as (A) flavoring agent.
The above-mentioned saccharin sodium and acesulfame potassium are known as non-saccharide synthetic sweeteners, and in the gargle of the present invention, they play a role as a sweetener and a flavoring agent. ) When used in combination with cellulose, it can also play a role in suppressing foaming when using gargles.
（Ｂ）多価アルコール脂肪酸エステル、
本発明のうがい薬は（Ｂ）多価アルコール脂肪酸エステルを含む。多価アルコール脂肪酸エステルは、一般に溶解補助剤として使用されることが多いが、本発明のうがい薬においては、うがい薬使用時の泡立ちを抑制する役割をも担うことができる。
前記（Ｂ）多価アルコール脂肪酸エステルの中でも、グリセリン脂肪酸エステルを好ましく用いることができる。
(B) polyhydric alcohol fatty acid ester,
The gargle of the present invention contains (B) a polyhydric alcohol fatty acid ester. Polyhydric alcohol fatty acid esters are generally often used as solubilizing agents, but in the gargle of the present invention, they can also play a role in suppressing foaming when the gargle is used.
Among the polyhydric alcohol fatty acid esters (B), glycerin fatty acid esters can be preferably used.
（Ｃ）セルロース類
本発明のうがい薬は（Ｃ）セルロース類を含む。セルロース類は、一般に粘稠化剤として粘度の調整（粘度増加）のために添加され得、うがい薬使用時の液垂れを防止する働きを担うとともに、うがい薬使用時の泡立ちを抑制する役割をも担うことができる。
前記（Ｃ）セルロース類の中でも、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース及びヒプロメロース（ヒドロキシプロピルメチルセルロース）からなる群から選択される１種以上を好ましく用いることができる
なお、これらセルロース類は、セルロース中のヒドロキシ基の置換度や粘度等によって種々のグレードが市販されており、うがい薬中の溶解性やうがい薬製品としての粘度を考慮し、種々選択できる。例えばヒプロメロースの場合、メトキシ基の置換度：２２～３０％、ヒドロキシプロポシ基の置換モル数：７～１２％、粘度（２０℃、２質量％水溶液）：３０００～５６００ｍＰａ・ｓであるものを選択することができるが、これに限定されない。
(C) Celluloses The gargle of the present invention contains (C) celluloses. Celluloses can generally be added as a thickening agent to adjust viscosity (increase viscosity), and play a role in preventing dripping when using gargles, as well as suppressing foaming when using gargles. can also take on the role.
Among the celluloses (C), one or more selected from the group consisting of hydroxyethylcellulose, hydroxypropylcellulose, and hypromellose (hydroxypropylmethylcellulose) can be preferably used. Various grades are commercially available depending on the degree of substitution, viscosity, etc., and various grades can be selected in consideration of solubility in gargles and viscosity as a gargle product. For example, in the case of hypromellose, the degree of substitution of methoxy groups: 22 to 30%, the number of moles substituted with hydroxypropoxy groups: 7 to 12%, and the viscosity (20°C, 2% by mass aqueous solution): 3000 to 5600 mPa・s You can choose, but are not limited to this.
（Ｄ）ポリオキシエチレン硬化ヒマシ油類
本発明のうがい薬は（Ｄ）ポリオキシエチレン硬化ヒマシ油類を含む。本成分は、ｌ－メントールやアズレンスルホン酸及び／又はその塩などの結晶析出を抑制する、可溶化剤としての働きを担うものである。
前記ポリオキシエチレン硬化ヒマシ油類の中でも、ポリオキシエチレン硬化ヒマシ油５、ポリオキシエチレン硬化ヒマシ油１０、ポリオキシエチレン硬化ヒマシ油２０、ポリオキシエチレン硬化ヒマシ油４０、ポリオキシエチレン硬化ヒマシ油５０、ポリオキシエチレン硬化ヒマシ油６０及びポリオキシエチレン硬化ヒマシ油１００等からなる群から選択される１種以上を好ましく用いることができる。
(D) Polyoxyethylene hydrogenated castor oil The gargle of the present invention contains (D) polyoxyethylene hydrogenated castor oil. This component functions as a solubilizer that suppresses crystal precipitation of l-menthol, azulene sulfonic acid and/or its salts, and the like.
Among the polyoxyethylene hydrogenated castor oils, polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50. , polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 100, etc., can be preferably used.
〈その他添加剤〉
本発明に係るうがい薬は、本発明の効果並びにうがい薬としての効果（薬効）を損なわない範囲において、前記以外の任意成分としてその他添加剤を配合してもよい。
以下に、その他添加剤として挙げられる代表的な成分を例示するが、これら例示に限定されるものではなく、うがい薬として慣用の各種添加剤を配合することができる。また、これら添加剤の添加的も下記のものに限定されない。
<Other additives>
The gargle according to the present invention may contain other additives as optional components other than those mentioned above, within a range that does not impair the effect of the present invention and the effect (medicinal efficacy) as a gargle.
Typical other additives are illustrated below, but the composition is not limited to these examples, and various additives commonly used in gargles can be blended. Moreover, the addition of these additives is not limited to the following.
消炎剤として、例えば、グリチルリチン酸二カリウム等を使用することができる。
殺菌剤として、例えば、ベンザルコニウム塩化物、ベンゼトニウム塩化物等を使用することができる。
前記（Ａ）以外の矯味剤として、例えば、カンフル、レモン油、ウイキョウ油、ユーカリ油、ケイヒ油、チョウジ油、バニリン、香料等を使用することができる。
安定化剤として、例えば、アスコルビン酸、ポリビニルアルコール、マクロゴール等を
使用することができる。
アルコール類として、例えば、エタノール、プロピルアルコール等のモノアルコール類、プロピレングリコール、ポリエチレングリコール、糖アルコール（マンニトール等）等の多価アルコール類が挙げられる。
糖アルコール類として、例えば、キシリトール、ソルビトール、グリセリン等を使用することができる。
キレート剤として、例えば、エデト酸ナトリウム、エデト酸カルシウム二ナトリウム、及びそれらの水和物等を使用することができる。
界面活性剤として、例えば、ラウリル硫酸ナトリウム、ショ糖脂肪酸エステル等を使用することができる。
等張化剤として、例えば、塩化ナトリウム、塩化マグネシウム等の無機塩類、プロピレングリコール、Ｄ－マンニトール等の多価アルコール類等を使用することができる。
防腐剤として、例えば、パラベン、チモール、ソルビン酸等を使用することができる。
溶解補助剤として、例えば、トリアセチン、白糖、ベンジルアルコール、ポリビニルピロリドン等を使用することができる。
粘稠（化）剤として、例えば、カルボキシビニルポリマー、カルメロースナトリウム、ゼラチン等を使用することができる。
ｐＨ調節剤として、例えば、クエン酸、乳酸、リン酸、炭酸、及びそれらの塩、それらの塩の水和物等が挙げられる。前記それらの塩、それらの塩の水和物としては、例えば、クエン酸ナトリウム水和物、クエン酸水和物、乳酸ナトリウム、リン酸水素ナトリウム、リン酸水素ナトリウム水和物、炭酸水素ナトリウム等を挙げることができる。
As an anti-inflammatory agent, for example, dipotassium glycyrrhizinate can be used.
As a disinfectant, for example, benzalkonium chloride, benzethonium chloride, etc. can be used.
As the flavoring agent other than the above (A), for example, camphor, lemon oil, fennel oil, eucalyptus oil, cinnamon oil, clove oil, vanillin, perfume, etc. can be used.
As a stabilizer, for example, ascorbic acid, polyvinyl alcohol, macrogol, etc. can be used.
Examples of alcohols include monoalcohols such as ethanol and propyl alcohol, and polyhydric alcohols such as propylene glycol, polyethylene glycol, and sugar alcohols (mannitol, etc.).
As sugar alcohols, for example, xylitol, sorbitol, glycerin, etc. can be used.
As the chelating agent, for example, sodium edetate, calcium disodium edetate, hydrates thereof, etc. can be used.
As the surfactant, for example, sodium lauryl sulfate, sucrose fatty acid ester, etc. can be used.
As the tonicity agent, for example, inorganic salts such as sodium chloride and magnesium chloride, polyhydric alcohols such as propylene glycol and D-mannitol, etc. can be used.
As preservatives, for example, parabens, thymol, sorbic acid, etc. can be used.
As the solubilizing agent, for example, triacetin, white sugar, benzyl alcohol, polyvinylpyrrolidone, etc. can be used.
As the thickening agent, for example, carboxyvinyl polymer, carmellose sodium, gelatin, etc. can be used.
Examples of the pH adjuster include citric acid, lactic acid, phosphoric acid, carbonic acid, salts thereof, and hydrates of these salts. Examples of the salts thereof and hydrates of these salts include sodium citrate hydrate, citric acid hydrate, sodium lactate, sodium hydrogen phosphate, sodium hydrogen phosphate hydrate, sodium hydrogen carbonate, etc. can be mentioned.
本発明のうがい薬において、各成分の配合量は、それら所望の効果を得ることができる配合量範囲であれば特に限定されず、例えば以下の通りとすることができる。なお本濃度は、うがい薬原液としての濃度であり、通常、うがい薬原液を１～３００倍に希釈して使用し、調整濃度によってはそのまま（希釈せずに）使用することもできる。
・アズレンスルホン酸及び／又はその塩：０．００１～０．６ｗ／ｖ％
・セチルピリジニウム及び／又はその塩：０．００１～１０ｗ／ｖ％
・ｌ－メントール：０．００１～１０ｗ／ｖ％
・（Ａ）サッカリンナトリウム及びアセスルファムカリウムから選択される１種以上の矯味剤：０．０５～２０ｗ／ｖ％
・（Ｂ）多価アルコール脂肪酸エステル：０．００１～５ｗ／ｖ％
・（Ｃ）セルロース類：０．００１～５ｗ／ｖ％
・（Ｄ）ポリオキシエチレン硬化ヒマシ油類：０．００１～５ｗ／ｖ％
In the gargle of the present invention, the amount of each component to be blended is not particularly limited as long as the desired effect can be obtained, and for example, it can be as follows. Note that this concentration is the concentration as a gargle undiluted solution, and the gargle undiluted solution is usually diluted 1 to 300 times before use, and depending on the adjusted concentration, it can also be used as is (without dilution).
・Azulene sulfonic acid and/or its salt: 0.001 to 0.6 w/v%
・Cetylpyridinium and/or its salt: 0.001-10w/v%
・L-menthol: 0.001-10w/v%
・(A) One or more flavoring agents selected from saccharin sodium and acesulfame potassium: 0.05 to 20 w/v%
・(B) Polyhydric alcohol fatty acid ester: 0.001 to 5 w/v%
・(C) Cellulose: 0.001 to 5 w/v%
・(D) Polyoxyethylene hydrogenated castor oil: 0.001 to 5 w/v%
本発明のうがい薬は、ポリエチレン（ＰＥ）、ポリプロピレン（ＰＰ）、ポリエチレンテレフタレート（ＰＥＴ）等の慣用の樹脂製容器や、ガラス製容器にて保存できる。また、容器の形状は特に限定されない。 The gargle of the present invention can be stored in a conventional resin container such as polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), or a glass container. Moreover, the shape of the container is not particularly limited.
［うがい薬の製造方法］
本発明のうがい薬の製造方法の一例を以下に挙げるが、本法に特に限定されることなく製造可能である。
例えば、セチルピリジニウム及び／又はその塩、ｌ－メントール、（Ｂ）多価アルコール脂肪酸エステル及び（Ｄ）ポリオキシエチレン硬化ヒマシ油類を混合してセチルピリジニウム相とする。セチルピリジニウム相調製時、必要により加熱を行ってもよいし、またアルコール類を添加するなどして溶解性を高めてもよい。なお調製時に系内に水が存在するとセチルピリジニウム相が泡立ち易くなり、泡立ちが収まるまで時間を要する場合がある。
セチルピリジニウム相とは別に、（Ａ）特定の矯味剤と（Ｃ）セルロース類、必要に応じて水を添加し、矯味剤相とする。
前記セチルピリジニウム相と矯味剤相を合わせて均一な相とした後、ここにアズレンスルホン酸及び／又はその塩、あるいは必要に応じてその水溶液を加えて溶解する。また前述の〈その他添加剤〉は、セチルピリジニウム相又は矯味剤相の調製時に添加してもよいし、これらを合わせて均一な相とする際、アズレンスルホン酸類を加える前又は後に、適時加えることができる。なおアズレンスルホン酸類を、各成分の溶解を確認した後に投入することで、各成分・添加剤の未溶解物や析出物を容易に確認できる。
またアズレンスルホン酸類を投入時、系内のｐＨを弱酸性（ｐＨ６．５～８．５）に維持することでアズレンスルホン酸類の安定性高めることができる（含量低下を抑制する）ことが期待できるため、必要に応じて系内のｐＨを調整することができる。
その後、必要により水を添加して容量補正し、うがい薬（原液）を得ることができる。
[Method for manufacturing gargle]
An example of the method for producing the gargle of the present invention is listed below, but the method can be produced without being particularly limited to this method.
For example, cetylpyridinium and/or its salt, 1-menthol, (B) polyhydric alcohol fatty acid ester, and (D) polyoxyethylene hydrogenated castor oil are mixed to form a cetylpyridinium phase. When preparing the cetylpyridinium phase, heating may be performed if necessary, and solubility may be increased by adding alcohols or the like. If water is present in the system during preparation, the cetylpyridinium phase tends to foam, and it may take some time for the foaming to subside.
Separately from the cetylpyridinium phase, (A) a specific flavoring agent, (C) cellulose, and if necessary, water are added to form a flavoring agent phase.
After the cetylpyridinium phase and the flavoring agent phase are combined to form a homogeneous phase, azulene sulfonic acid and/or a salt thereof, or an aqueous solution thereof if necessary, is added and dissolved therein. In addition, the above-mentioned <other additives> may be added when preparing the cetylpyridinium phase or the flavoring agent phase, or when combining them to form a homogeneous phase, they may be added at an appropriate time before or after adding the azulene sulfonic acids. I can do it. By adding the azulene sulfonic acids after confirming the dissolution of each component, undissolved substances and precipitates of each component and additive can be easily confirmed.
In addition, by maintaining the pH in the system at a weakly acidic level (pH 6.5 to 8.5) when adding azulene sulfonic acids, it is expected that the stability of azulene sulfonic acids can be increased (suppressing the decrease in content). Therefore, the pH within the system can be adjusted as necessary.
Thereafter, if necessary, water can be added to correct the volume to obtain a gargle (undiluted solution).
以下、本発明を実施例により、さらに詳しく説明する。ただし、本発明はこれら実施例に限定されるものではない。 Hereinafter, the present invention will be explained in more detail with reference to Examples. However, the present invention is not limited to these examples.
［うがい薬原液及びうがい薬の調製（１）］
〈実施例１〉
ポリオキシエチレン硬化ヒマシ油６０ ０．１ｇを加熱して溶解後、プロピレングリコール ５５ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル
０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール ５ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム ２．５ｇ及びヒドロキシエチルセルロースＳＥ－６００ ０．１ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇを加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例１のうがい薬原液を得た（表１）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例１のうがい薬を得た（表２）。
〈実施例２〉
実施例１のサッカリンナトリウムを、アセスルファムカリウムに変えたほかは実施例１と同様にして、実施例２のうがい薬原液及びうがい薬を得た。
[Preparation of gargle stock solution and gargle (1)]
<Example 1>
0.1 g of polyoxyethylene hydrogenated castor oil 60 was heated and dissolved, and then dissolved in 55 g of propylene glycol. To this, 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 5 g of l-menthol were added and dissolved by stirring at room temperature to form a cetylpyridinium phase.
Next, 2.5 g of saccharin sodium and 0.1 g of hydroxyethyl cellulose SE-600 were added to 30 g of purified water and dissolved by stirring at room temperature to form a flavoring agent phase.
After adding the flavoring agent phase to the cetylpyridinium phase and dissolving it by stirring at room temperature, 0.5 g of sodium azulene sulfonate was added and dissolved, and purified water was added to make a total volume of 100 mL. A drug stock solution was obtained (Table 1).
0.4 mL of the gargle stock solution was diluted with 100 mL of water to obtain the gargle of Example 1 (Table 2).
<Example 2>
A gargle stock solution and a gargle of Example 2 were obtained in the same manner as in Example 1 except that saccharin sodium in Example 1 was replaced with acesulfame potassium.
〈比較例１〉
実施例１のサッカリンナトリウムを、グリチルリチン酸二カリウムに変えたほかは実施例１と同様にして、比較例１のうがい薬原液及びうがい薬を得た。
〈比較例２〉
実施例１のサッカリンナトリウムを配合しなかったほかは実施例１と同様にして、比較例２のうがい薬原液及びうがい薬を得た。
〈比較例３〉
実施例１のヒドロキシエチルセルロースＳＥ－６００を配合しなかったほかは実施例１と同様にして、比較例３のうがい薬原液及びうがい薬を得た。
〈比較例４〉
実施例１のグリセリン脂肪酸エステルを配合しなかったほかは実施例１と同様にして、比較例４のうがい薬原液及びうがい薬を得た。
〈比較例５〉
実施例１のヒドロキシエチルセルロースＳＥ－６００及びグリセリン脂肪酸エステルを配合しなかったほかは実施例１と同様にして、比較例５のうがい薬原液及びうがい薬を得た。
〈比較例６〉
実施例１のポリオキシエチレン硬化ヒマシ油６０を配合しなかったほかは実施例１と同
様にして、比較例６のうがい薬原液及びうがい薬を得た。
〈比較例７〉
実施例１のサッカリンナトリウム、ヒドロキシエチルセルロースＳＥ－６００、グリセリン脂肪酸エステル及びポリオキシエチレン硬化ヒマシ油６０を配合しなかったほかは実施例１と同様にして、比較例７のうがい薬原液及びうがい薬を得た。
<Comparative example 1>
A gargle stock solution and a gargle of Comparative Example 1 were obtained in the same manner as in Example 1 except that the saccharin sodium in Example 1 was changed to dipotassium glycyrrhizinate.
<Comparative example 2>
A gargle stock solution and a gargle of Comparative Example 2 were obtained in the same manner as in Example 1, except that the saccharin sodium of Example 1 was not blended.
<Comparative example 3>
A gargle stock solution and a gargle of Comparative Example 3 were obtained in the same manner as in Example 1 except that hydroxyethyl cellulose SE-600 of Example 1 was not blended.
<Comparative example 4>
A gargle stock solution and a gargle of Comparative Example 4 were obtained in the same manner as in Example 1 except that the glycerin fatty acid ester of Example 1 was not blended.
<Comparative example 5>
A gargle stock solution and a gargle of Comparative Example 5 were obtained in the same manner as in Example 1, except that hydroxyethylcellulose SE-600 and glycerin fatty acid ester of Example 1 were not blended.
<Comparative example 6>
A gargle stock solution and a gargle of Comparative Example 6 were obtained in the same manner as in Example 1, except that the polyoxyethylene hydrogenated castor oil 60 of Example 1 was not blended.
<Comparative example 7>
A gargle stock solution and a gargle of Comparative Example 7 were obtained in the same manner as in Example 1, except that saccharin sodium, hydroxyethyl cellulose SE-600, glycerin fatty acid ester, and polyoxyethylene hydrogenated castor oil 60 of Example 1 were not blended. Ta.
実施例１～２及び比較例１～７で調製したうがい薬原液の処方を表１に、またうがい薬（希釈後）の処方を表２に、夫々示す。 The formulations of the gargle stock solutions prepared in Examples 1 to 2 and Comparative Examples 1 to 7 are shown in Table 1, and the formulations of the gargles (after dilution) are shown in Table 2, respectively.
［試験例１：使用感（矯味）］
実施例１～２及び比較例１～７のうがい薬を、適量口に含み、下記基準により官能評価を行った。
＜使用感（矯味） 評価基準＞
〇：苦味を感じにくく、うがいしやすい（矯味を感じる）
△：苦味が僅かにあり、うがいがしにくい（わずかに矯味を感じる）
×：苦味があり、うがいに困難を感じる（矯味を感じない）
[Test Example 1: Usage feeling (flavor correction)]
Appropriate amounts of the gargles of Examples 1 to 2 and Comparative Examples 1 to 7 were placed in the mouth, and sensory evaluation was performed according to the following criteria.
<Feeling of use (flavor correction) evaluation criteria>
〇: Hard to feel bitter taste, easy to gargle (feels taste correction)
△: Slightly bitter taste, difficult to gargle (slightly tasteless)
×: Has a bitter taste and makes gargling difficult (no taste correction)
［試験例２：泡立ち抑制評価］
ＪＩＳの泡立ち試験を参照（ＪＩＳ Ｋ３３６２－２００８ ８．５起泡力及び泡の安定度、ロス・マイルス法参照）し、以下の手順にて実施例１～２及び比較例１～７のうがい薬の泡立ち試験を行った。
５０ｍＬビュレットに各うがい薬（検体）約５０ｍＬを入れ、更に、１００ｍＬメスシリンダーに前記検体約２０ｍＬを加え、ビュレットの先端（コック側）からメスシリンダー中の検液の液面まで約４５ｃｍとなるようにビュレットを設置した。
ビュレットのコックを全開にし、全量をメスシリンダーに加え、直ちに生じた泡の高さを測定し、下記基準により泡立ち抑制について評価した。
＜泡立ち抑制 評価基準＞
〇：０～２０ｃｍ
△：２１～４０ｃｍ
×：４１ｃｍ以上
[Test Example 2: Foaming suppression evaluation]
Referring to the JIS foaming test (JIS K3362-2008 8.5 Foaming power and foam stability, Ross-Miles method), the gargles of Examples 1 to 2 and Comparative Examples 1 to 7 were tested using the following procedure. A foaming test was conducted.
Pour about 50 mL of each gargle (specimen) into a 50 mL buret, then add about 20 mL of the sample into a 100 mL graduated cylinder, so that the distance from the tip of the buret (cock side) to the liquid level of the test solution in the graduated cylinder is about 45 cm. A burette was installed on the
The cock of the buret was fully opened, the entire amount was added to the measuring cylinder, the height of the foam generated was immediately measured, and foaming suppression was evaluated according to the following criteria.
<Foaming suppression evaluation criteria>
〇：0～20cm
△: 21-40cm
×: 41cm or more
［試験例３：液垂れ抑制評価］
一般にうがい薬は、うがい薬（原液）の入った容器から付属するカップやコップ等に適量を量り取り、これを水で希釈して使用（含嗽）する。以下の手順にて、うがい薬（原液）をコップ等にとる際の液垂れ性を評価した。
プラスチック容器（市販のうがい薬容器）に実施例１～２及び比較例１～７のうがい薬原液を適量充填した。うがい薬使用時と同様に、付属コップに約０．４ｍＬのうがい薬原液を量り取る時の液垂れ抑制について下記基準により評価した。
＜液垂れ抑制 評価基準＞
〇：液垂れせずに量り取れる
×：液垂れし、使用しにくい
[Test Example 3: Dripping suppression evaluation]
Generally, gargles are used by measuring an appropriate amount from a container containing the gargle (undiluted solution) into an attached cup or cup, diluting it with water, and using it (gargling). The following procedure was used to evaluate the dripping properties of the gargle (undiluted solution) when taken into a cup or the like.
Plastic containers (commercially available gargle containers) were filled with appropriate amounts of the gargle stock solutions of Examples 1 to 2 and Comparative Examples 1 to 7. As in the case of using the gargle, the suppression of dripping when approximately 0.4 mL of the gargle stock solution was measured into the attached cup was evaluated according to the following criteria.
<Dripping suppression evaluation criteria>
〇: Can be measured without dripping ×: Difficult to use due to dripping
［試験例４：結晶析出抑制評価］
実施例１～２及び比較例１～７のうがい薬を、一夜室温で放置し、目視にて結晶析出の有無を確認し、結晶析出の抑制について下記基準により評価した。
＜結晶析出抑制 評価基準＞
〇：結晶析出しない
×：結晶析出する
[Test Example 4: Crystal precipitation suppression evaluation]
The gargles of Examples 1 to 2 and Comparative Examples 1 to 7 were left at room temperature overnight, and the presence or absence of crystal precipitation was visually confirmed, and the suppression of crystal precipitation was evaluated according to the following criteria.
<Evaluation criteria for suppressing crystal precipitation>
〇: No crystal precipitation ×: Crystal precipitation
表２に示すように、（Ａ）矯味剤としてサッカリンナトリウム（実施例１）及びアセスルファムカリウム（実施例２）を配合したうがい薬は、使用感（うがいのしやすさ（矯味（苦味の抑制など））に優れ、泡立ち抑制、液垂れ抑制及び結晶析出抑制をしていたが、従来矯味剤としても配合されているグリチルリチン酸二カリウム（比較例１）を配合したうがい薬は、使用感が悪いとする結果となった。
（Ａ）矯味剤（サッカリンナトリウム、アセスルファムカリウム）を配合しないうがい薬（比較例２）は、使用感が著しく悪く、しかも後述する（Ｃ）セルロース類や、泡立ち抑制への寄与が期待できる界面活性剤とされる（Ｂ）多価アルコール脂肪酸エステルを配合していても、泡立ち抑制に至らなかった。（Ｃ）セルロース類（ヒドロキシエチルセルロース）を配合しないうがい薬（比較例３）は、液垂れが著しく生じ、また泡立ち抑制効果も低いとする結果となった。（Ｂ）多価アルコール脂肪酸エステル（グリセリン脂肪酸エステル）を配合しないうがい薬（比較例４）は、泡立ち抑制効果が低いとする結果となった。更に、（Ｃ）セルロース類（ヒドロキシエチルセルロース）及び（Ｂ）多価アルコール脂肪酸エステル（グリセリン脂肪酸エステル）を配合しないうがい薬（比較例５）も
、泡立ち抑制効果が低い結果となった。
一方、結晶析出抑制に寄与する（Ｄ）ポリオキシエチレン硬化ヒマシ油類を配合しないうがい薬（比較例６）は、結晶析出抑制効果が低かった。
また、（Ａ）矯味剤（サッカリンナトリウム、アセスルファムカリウム）、（Ｂ）多価アルコール脂肪酸エステル（グリセリン脂肪酸エステル）、（Ｃ）セルロース類（ヒドロキシエチルセルロース）及び（Ｄ）ポリオキシエチレン硬化ヒマシ油類をいずれも非配合としたうがい薬（比較例７）は、使用感が悪く、泡立ち、液垂れ及び結晶析出抑制効果が低かった。
なお本処方では、糖類の泡立ち抑制効果及びｌ－メントールの結晶析出抑制効果を明確とするため、一般的な処方と比べて糖類並びにｌ－メントールを多めに配合しており、またそのため、この一連の試験に係る評価基準は、後述する同様の試験における評価基準とは異なることがある。
As shown in Table 2, (A) gargles containing saccharin sodium (Example 1) and acesulfame potassium (Example 2) as flavoring agents have improved usability (easiness of gargling, taste correction (suppression of bitterness, etc.)). ), and suppressed foaming, dripping, and crystal precipitation. However, the gargle containing dipotassium glycyrrhizinate (Comparative Example 1), which is conventionally used as a flavoring agent, had a poor feel when used. The result was that.
(A) A gargle that does not contain flavoring agents (saccharin sodium, acesulfame potassium) (Comparative Example 2) has an extremely poor feeling of use; Even if polyhydric alcohol fatty acid ester (B), which is said to be ester, was blended, foaming was not suppressed. (C) A gargle containing no cellulose (hydroxyethylcellulose) (Comparative Example 3) resulted in significant dripping and a low foaming suppressing effect. (B) The gargle containing no polyhydric alcohol fatty acid ester (glycerin fatty acid ester) (Comparative Example 4) was found to have a low foaming suppressing effect. Furthermore, the gargle (Comparative Example 5) that did not contain (C) cellulose (hydroxyethyl cellulose) and (B) polyhydric alcohol fatty acid ester (glycerin fatty acid ester) also had a low foaming suppressing effect.
On the other hand, the gargle that did not contain (D) polyoxyethylene hydrogenated castor oil, which contributes to suppressing crystal precipitation (Comparative Example 6), had a low crystal precipitation suppressing effect.
In addition, (A) flavoring agents (saccharin sodium, acesulfame potassium), (B) polyhydric alcohol fatty acid esters (glycerin fatty acid esters), (C) celluloses (hydroxyethyl cellulose), and (D) polyoxyethylene hydrogenated castor oils. The gargle (Comparative Example 7) that did not contain the gargle had a poor feeling of use, and had a low effect of suppressing foaming, dripping, and crystal precipitation.
In addition, in this formulation, in order to clarify the foaming suppressing effect of sugars and the crystal precipitation suppressing effect of l-menthol, more sugars and l-menthol are blended compared to general formulations, and for this reason, this series The evaluation criteria for this test may differ from the evaluation criteria for similar tests described below.
［うがい薬原液及びうがい薬の調製（２）］
〈実施例３〉
ポリオキシエチレン硬化ヒマシ油６０ ０．１ｇを加熱して溶解後、プロピレングリコール ５０ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル
０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール １ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム １ｇ及びヒプロメロース６０ＳＨ－４０００ ０．１ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇ及び適量のｐＨ調節剤を加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例３のうがい薬原液（ｐＨ７．５）を得た（表３）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例３のうがい薬を得た（表４）。
〈実施例４〉
実施例３のヒプロメロース６０ＳＨ－４０００の配合量を０．１２ｇに変えたほかは実施例３と同様にして、実施例４のうがい薬原液及びうがい薬を得た。
〈実施例５〉
実施例３のヒプロメロース６０ＳＨ－４０００をヒプロメロース９０ＳＨ－４０００ＳＲに変え、配合量を０．１５ｇに変えたほかは実施例３と同様にして、実施例５のうがい薬原液及びうがい薬を得た。
〈実施例６〉
実施例３のヒプロメロース６０ＳＨ－４０００をヒドロキシエチルセルロースＳＥ－９００に変えたほかは実施例３と同様にして、実施例６のうがい薬原液及びうがい薬を得た。
[Preparation of gargle stock solution and gargle (2)]
<Example 3>
0.1 g of polyoxyethylene hydrogenated castor oil 60 was heated and dissolved, and then dissolved in 50 g of propylene glycol. To this, 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of l-menthol were added and dissolved by stirring at room temperature to form a cetylpyridinium phase.
Next, 1 g of saccharin sodium and 0.1 g of hypromellose 60SH-4000 were added to 30 g of purified water and dissolved by stirring at room temperature to form a flavoring agent phase.
Add the flavoring agent phase to the cetylpyridinium phase and dissolve by stirring at room temperature, then add and dissolve 0.5 g of sodium azulene sulfonate and an appropriate amount of pH adjuster, and add purified water to bring the total volume to 100 mL. , the gargle stock solution (pH 7.5) of Example 3 was obtained (Table 3).
0.4 mL of the gargle stock solution was diluted with 100 mL of water to obtain the gargle of Example 3 (Table 4).
<Example 4>
A gargle stock solution and a gargle of Example 4 were obtained in the same manner as in Example 3, except that the amount of hypromellose 60SH-4000 in Example 3 was changed to 0.12 g.
<Example 5>
A gargle stock solution and a gargle of Example 5 were obtained in the same manner as in Example 3, except that hypromellose 60SH-4000 in Example 3 was replaced with hypromellose 90SH-4000SR and the blended amount was changed to 0.15 g.
<Example 6>
A gargle stock solution and a gargle of Example 6 were obtained in the same manner as in Example 3, except that hypromellose 60SH-4000 in Example 3 was replaced with hydroxyethylcellulose SE-900.
〈比較例８〉
実施例３のヒプロメロース６０ＳＨ－４０００を配合しないほかは実施例３と同様にして、比較例８のうがい薬原液及びうがい薬を得た。
<Comparative example 8>
A gargle stock solution and a gargle of Comparative Example 8 were obtained in the same manner as in Example 3, except that hypromellose 60SH-4000 of Example 3 was not blended.
実施例３～６及び比較例８で調製したうがい薬原液の処方を表３に、またうがい薬（希釈後）の処方を表４に、夫々示す。 The prescriptions of the gargle stock solutions prepared in Examples 3 to 6 and Comparative Example 8 are shown in Table 3, and the prescriptions of the gargles (after dilution) are shown in Table 4, respectively.
［試験例５：粘度評価］
実施例３～６及び比較例８のうがい薬原液１００ｍＬが入った１００ｍＬのビーカーを用意し、室温（２０±５℃）下、回転粘度計（ＶＩＳＣＯＭＥＴＥＲ ＴＶ－１０、東機産業（株））を用いて試験を行った。ローターはＭ－１ローターを用い、回転速度１００ｒｐｍで１２０秒間測定を行った。
なお、粘度が１０ｍＰａ・ｓ以下であると、うがい薬原液として粘度が低く、これを量り取る際に液垂れを生じやすくなるとが懸念される。
[Test Example 5: Viscosity evaluation]
A 100 mL beaker containing 100 mL of the gargle stock solutions of Examples 3 to 6 and Comparative Example 8 was prepared, and a rotational viscometer (VISCOMETER TV-10, Toki Sangyo Co., Ltd.) was measured at room temperature (20±5°C). The test was conducted using An M-1 rotor was used as the rotor, and the measurement was performed at a rotation speed of 100 rpm for 120 seconds.
In addition, if the viscosity is 10 mPa·s or less, the viscosity is low as a gargle drug stock solution, and there is a concern that dripping may occur when measuring this.
また、実施例３～６及び比較例８のうがい薬原液について、前述の［試験例３：液垂れ抑制評価］の手順に従い、うがい薬原液を量り取る時の液垂れ抑制について評価した。
これらの結果をあわせて表４に示す。
In addition, the gargle stock solutions of Examples 3 to 6 and Comparative Example 8 were evaluated for dripping prevention when weighing out the gargle stock solutions according to the procedure of [Test Example 3: Dripping Prevention Evaluation] described above.
These results are shown in Table 4.
本処方では、粘稠化剤であるヒドロキシエチルセルロースＳＥ－９００、ヒプロメロース６０ＳＨ－４０００及びヒプロメロース９０ＳＨ－４０００ＳＲの配合量を変えた製剤の粘度と液垂れ抑制効果を評価した。
粘稠化剤を配合していない比較例８では、うがい薬原液の粘度が１０ｍＰａ・ｓ以下となり、また原液を量り取る際に液垂れし、使用しにくいとする結果となった。それに対して、粘稠化剤を０．１０％～０．１５％配合した実施例３～６のうがい薬原液では、使用した粘稠化剤の種類やグレードによらず粘度が１５ｍＰａ・ｓ以上となり、液垂れせずに量り取れた。
In this formulation, the viscosity and dripping suppressing effect of formulations with varying amounts of thickening agents hydroxyethylcellulose SE-900, hypromellose 60SH-4000, and hypromellose 90SH-4000SR were evaluated.
In Comparative Example 8, which did not contain a thickening agent, the viscosity of the gargle stock solution was 10 mPa·s or less, and the stock solution dripped when measured out, making it difficult to use. On the other hand, the gargle stock solutions of Examples 3 to 6 containing 0.10% to 0.15% of the thickening agent had a viscosity of 15 mPa・s or more regardless of the type or grade of the thickening agent used. It was possible to measure the liquid without dripping.
［うがい薬原液及びうがい薬の調製（３）］
〈実施例７〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０） ０．５ｇを加熱して溶解後、プロピレングリコール ５５ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル ０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール １ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム １ｇ及びヒプロメロース（メトロー
ズ９０ＳＨ－４０００ＳＲ） ０．５ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇを加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例７のうがい薬原液を得た（表５）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例７のうがい薬を得た（表６）。
〈実施例８〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレン硬化ヒマシ油５０（ニッコールＨＣＯ－５０）に変えたほかは、実施例７と同様にして実施例８のうがい薬原液及びうがい薬を得た。
〈実施例９〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレン硬化ヒマシ油６０（ニッコールＨＣＯ－６０）に変えたほかは、実施例７と同様にして実施例９のうがい薬原液及びうがい薬を得た。
〈実施例１０〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレン硬化ヒマシ油１００（ニッコールＨＣＯ－１００）に変えたほかは、実施例７と同様にして実施例１０のうがい薬原液及びうがい薬を得た。
[Preparation of gargle stock solution and gargle (3)]
<Example 7>
After heating and dissolving 0.5 g of polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40), it was dissolved in 55 g of propylene glycol. To this, 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of l-menthol were added and dissolved by stirring at room temperature to form a cetylpyridinium phase.
Next, 1 g of saccharin sodium and 0.5 g of hypromellose (Metrose 90SH-4000SR) were added to 30 g of purified water and dissolved by stirring at room temperature to form a flavoring agent phase.
The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, then 0.5 g of sodium azulene sulfonate was added and dissolved, and purified water was added to make a total volume of 100 mL. A drug stock solution was obtained (Table 5).
0.4 mL of the gargle stock solution was diluted with 100 mL of water to obtain the gargle of Example 7 (Table 6).
<Example 8>
The gargle stock solution and gargle of Example 8 were prepared in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was changed to polyoxyethylene hydrogenated castor oil 50 (Nikkor HCO-50). Got medicine.
<Example 9>
The gargle stock solution and gargle of Example 9 were prepared in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was changed to polyoxyethylene hydrogenated castor oil 60 (Nikkor HCO-60). Got medicine.
<Example 10>
The gargle stock solution and gargle of Example 10 were prepared in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was changed to polyoxyethylene hydrogenated castor oil 100 (Nikkor HCO-100). Got medicine.
〈比較例９〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリラウリン酸デカグリセリル（ニッコールＤｅｃａｇｌｙｎ １－Ｌ）に変えたほかは、実施例７と同様にして比較例Ａのうがい薬原液を得た（表Ａ）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、比較例Ａのうがい薬を得た（表Ｂ）。
〈比較例１０〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート２０（ニッコールＴＬ－１０）に変えたほかは、実施例７と同様にして比較例１０のうがい薬原液及びうがい薬を得た。
〈比較例１１〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート４０（ニッコールＴＰ－１０ＥＸ）に変えたほかは、実施例７と同様にして比較例１１のうがい薬原液及びうがい薬を得た。
〈比較例１２〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート６０（ニッコールＴＳ－１０ＭＶ）に変えたほかは、実施例７と同様にして比較例１２のうがい薬原液及びうがい薬を得た。
〈比較例１３〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート８０（ニッコールＴＯ－１０ＭＶ）に変えたほかは、実施例７と同様にして比較例１３のうがい薬原液及びうがい薬を得た。
〈比較例１４〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ラウロマクロゴール（ニッコールＢＬ－２１）に変えたほかは、実施例７と同様にして比較例１４のうがい薬原液及びうがい薬を得た。
〈比較例１５〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ラウロマクロゴール（ニッコールＢＬ－２５）に変えたほかは、実施例７と同様にして比較例１５のうがい薬原液及びうがい薬を得た。
〈比較例１６〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレンオレイルエーテル（ニッコールＢＯ－２０Ｖ）に変えたほかは、実施例７と同様にして比較例１６のうがい薬原液及びうがい薬を得た。
〈比較例１７〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレンオレイルエーテル（ニッコールＢＯ－５０Ｖ）に変えたほかは、実施例７と同様にして比較例１７のうがい薬原液及びうがい薬を得た。
<Comparative example 9>
A gargle stock solution of Comparative Example A was obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was replaced with decaglyceryl polylaurate (Nikkor Decaglyn 1-L). Table A).
0.4 mL of the gargle stock solution was diluted with 100 mL of water to obtain a gargle of Comparative Example A (Table B).
<Comparative example 10>
A gargle stock solution and a gargle of Comparative Example 10 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was replaced with polysorbate 20 (Nikkor TL-10).
<Comparative example 11>
A gargle stock solution and a gargle of Comparative Example 11 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was replaced with polysorbate 40 (Nikkor TP-10EX).
<Comparative example 12>
A gargle stock solution and gargle of Comparative Example 12 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was replaced with polysorbate 60 (Nikkor TS-10MV).
<Comparative example 13>
A gargle stock solution and gargle of Comparative Example 13 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was replaced with polysorbate 80 (Nikkor TO-10MV).
<Comparative example 14>
A gargle stock solution and gargle of Comparative Example 14 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was changed to lauromacrogol (Nikkor BL-21). .
<Comparative example 15>
A gargle stock solution and gargle of Comparative Example 15 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was changed to lauromacrogol (Nikkor BL-25). .
<Comparative example 16>
The gargle stock solution and gargle of Comparative Example 16 were prepared in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was changed to polyoxyethylene oleyl ether (Nikkor BO-20V). Obtained.
<Comparative example 17>
The gargle stock solution and gargle of Comparative Example 17 were prepared in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkor HCO-40) was changed to polyoxyethylene oleyl ether (Nikkor BO-50V). Obtained.
実施例７～１０及び比較例９～１７で調製したうがい薬原液の処方を表５に、またうがい薬（希釈後）の処方を表６に、夫々示す。 The prescriptions of the gargle stock solutions prepared in Examples 7 to 10 and Comparative Examples 9 to 17 are shown in Table 5, and the prescriptions of the gargles (after dilution) are shown in Table 6, respectively.
［試験例６：アズレンスルホン酸ナトリウム添加前のうがい薬原液の外観評価］
アズレンスルホン酸ナトリウムを添加すると濃紺色となり、うがい薬原液の外観（濁り等）が評価できないため、アズレンスルホン酸ナトリウム添加前にうがい薬原液の外観を
評価した。
実施例７～１０及び比較例９～１７のうがい薬原液の外観を、アズレンスルホン酸ナトリウム添加前に、下記基準により目視にて評価を行った。得られた結果を表７に示す。
＜アズレンスルホン酸ナトリウム添加前のうがい薬原液の外観 評価基準＞
〇：澄明である
△：わずかに濁りがある
×：濁りがある
[Test Example 6: Appearance evaluation of gargle stock solution before addition of sodium azulene sulfonate]
When sodium azulene sulfonate was added, it turned dark blue and the appearance (turbidity, etc.) of the gargle stock solution could not be evaluated, so the appearance of the stock gargle solution was evaluated before adding sodium azulene sulfonate.
The appearance of the gargle stock solutions of Examples 7 to 10 and Comparative Examples 9 to 17 was visually evaluated according to the following criteria before adding sodium azulene sulfonate. The results obtained are shown in Table 7.
<Appearance evaluation criteria of gargle stock solution before addition of sodium azulene sulfonate>
〇: Clear △: Slightly cloudy ×: Cloudy
［試験例７：うがい薬（希釈後）の使用感（甘味）］
実施例７～１０及び比較例９～１７のうがい薬（希釈後）を適量口に含み、使用感（甘味）を、官能試験で下記基準により評価を行った。得られた結果を表７に示す。
＜うがい薬（希釈後）の使用感（甘味） 評価基準＞
〇：甘味があり、うがいしやすい
△：やや甘味があるが、うがいしにくい
×：甘味がなく、うがいに困難を感じる
[Test Example 7: Usage sensation (sweet taste) of gargle (after dilution)]
Appropriate amounts of the gargles (after dilution) of Examples 7 to 10 and Comparative Examples 9 to 17 were placed in the mouth, and the feeling of use (sweetness) was evaluated using the following criteria in a sensory test. The results obtained are shown in Table 7.
<Usability (sweetness) of gargle (after dilution) Evaluation criteria>
〇: Sweet taste, easy to gargle △: Slightly sweet taste, but difficult to gargle ×: No sweet taste, difficult to gargle
［試験例８：うがい薬原液の滴下（希釈操作時）における結晶析出評価］
５０ｍＬビーカーに水道水５０ｍＬを入れ、そこに実施例７～１０及び比較例９～１７のうがい薬原液を適量滴下した。滴下して５分間放置後、結晶析出の有無を目視にて確認し、下記基準により評価した。得られた結果を表７に示す。
＜うがい薬原液の滴下（希釈操作時）の結晶析出 評価基準＞
〇：結晶析出しない
×：結晶析出した
[Test Example 8: Evaluation of crystal precipitation during dropping of gargle drug stock solution (during dilution operation)]
50 mL of tap water was placed in a 50 mL beaker, and appropriate amounts of the gargle stock solutions of Examples 7 to 10 and Comparative Examples 9 to 17 were dropped therein. After dropping and leaving for 5 minutes, the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria. The results obtained are shown in Table 7.
<Evaluation criteria for crystal precipitation during dripping of gargle drug stock solution (during dilution operation)>
〇: Crystals did not precipitate ×: Crystals precipitated
［試験例９：うがい薬（希釈後）の液の濁度評価］
実施例７～１０及び比較例９～１７のうがい薬を調製後、紫外可視分光光度計（ＵＶ－１６００、（株）島津製作所）を用いて、波長６６０ｎｍの濁度（ＯＤ６６０）を測定し、下記評価基準にて評価した。得られた結果を表７に示す。なお濁りが生じると結晶析出しやすいため、濁度測定は結晶析出の一つの指標といえる。
＜うがい薬（希釈後）の液の濁度（濁度：ＯＤ６６０） 評価基準＞
〇：０．０３５以下
△：０．０３５～０．０４４
×：０．０４５以上
[Test Example 9: Evaluation of turbidity of gargle (after dilution)]
After preparing the gargles of Examples 7 to 10 and Comparative Examples 9 to 17, the turbidity (OD 660 ) at a wavelength of 660 nm was measured using an ultraviolet-visible spectrophotometer (UV-1600, Shimadzu Corporation). , evaluated using the following evaluation criteria. The results obtained are shown in Table 7. Note that when turbidity occurs, crystals tend to precipitate, so turbidity measurement can be said to be one indicator of crystal precipitation.
<Evaluation criteria for turbidity of gargle (after dilution) (turbidity: OD 660 )>
〇: 0.035 or less △: 0.035 to 0.044
×: 0.045 or more
［試験例１０：うがい薬（希釈後）の低温下における結晶析出評価］
実施例７～１０及び比較例９～１７のうがい薬を、一夜５℃で保存し、目視にて結晶析出の有無を確認し、結晶析出の抑制について下記基準により評価した。得られた結果を表７に示す。
＜うがい薬（希釈後）低温（５℃）下の結晶析出 評価基準＞
〇：結晶析出せず、液が澄明である。
△：結晶析出しないが、液が濁る。
×：結晶析出する。
[Test Example 10: Evaluation of crystal precipitation of gargle (after dilution) at low temperature]
The gargles of Examples 7 to 10 and Comparative Examples 9 to 17 were stored at 5°C overnight, and the presence or absence of crystal precipitation was visually confirmed, and the suppression of crystal precipitation was evaluated according to the following criteria. The results obtained are shown in Table 7.
<Evaluation criteria for crystal precipitation at low temperature (5℃) after dilution of mouthwash>
○: No crystals precipitated and the liquid was clear.
Δ: No crystal precipitation occurs, but the liquid becomes cloudy.
x: Crystals precipitate.
［試験例１１：うがい薬（希釈後）の泡立ち抑制評価］
ＪＩＳの泡立ち試験を参照（ＪＩＳ Ｋ３３６２－２００８ ８．５起泡力及び泡の安定度、ロス・マイルス法参照）し、以下の手順にて実施例７～１０及び比較例９～１７のうがい薬の泡立ち試験を行った。
５０ｍＬビュレットに各うがい薬（検体）約５０ｍＬを入れ、更に、１００ｍＬメスシリンダーに前記検体約２０ｍＬを加え、ビュレットの先端（コック側）からメスシリンダー中の検液の液面まで約４５ｃｍとなるようにビュレットを設置した。
ビュレットのコックを全開にし、全量をメスシリンダーに加え、直ちに生じた泡の高さを測定し、下記基準により泡立ち抑制について評価し、得られた結果を表７に示す。
＜うがい薬（希釈後）泡立ち抑制 評価基準＞
〇：０～１０ｃｍ
△：１０．５～１２．５ｃｍ
×：１３．０ｃｍ以上
[Test Example 11: Foaming suppression evaluation of gargle (after dilution)]
Referring to the JIS foaming test (JIS K3362-2008 8.5 Foaming power and foam stability, Ross-Miles method), the gargles of Examples 7 to 10 and Comparative Examples 9 to 17 were tested using the following procedure. A foaming test was conducted.
Pour about 50 mL of each gargle (specimen) into a 50 mL buret, then add about 20 mL of the sample into a 100 mL graduated cylinder, so that the distance from the tip of the buret (cock side) to the liquid level of the test solution in the graduated cylinder is about 45 cm. A burette was installed on the
The cock of the burette was fully opened, the entire amount was added to the graduated cylinder, the height of the foam produced was immediately measured, and foaming suppression was evaluated according to the following criteria. Table 7 shows the results obtained.
<Gargle (after dilution) foaming suppression evaluation criteria>
〇: 0-10cm
△: 10.5-12.5cm
×: 13.0cm or more
本処方では、うがい薬原液中の室温における結晶析出（原液の外観）、またうがい薬原液の滴下（希釈操作時）の結晶析出及びうがい薬（希釈後）の液の濁度並びに低温（５℃）下における結晶析出を抑制する目的で、ポリオキシエチレン硬化ヒマシ油類の代わりに
可溶化剤として知られている界面活性剤を種々変更して配合した場合の効果を評価した。またうがい薬の使用感（希釈後の甘味）や（希釈後の）泡立ち抑制についても評価した。
本発明の（Ｄ）成分であるポリオキシエチレン硬化ヒマシ油類は、希釈操作時の結晶析出抑制効果（原液の滴下）及びうがい薬（希釈後）の使用感（甘味）が多少低下するグレードがあるものの、原液の外観、結晶析出抑制効果（液の濁度、低温下における結晶析出）及び泡立ち抑制効果は良好であり、すべての評価において概ね満足できる結果となった。（実施例７～１０）
可溶化剤としてラウリン酸デカグリセリルを用いた場合、うがい薬原液の滴下（希釈操作時）において結晶析出が確認され、また原液の外観に濁りが生じ、うがい薬（希釈後）の使用感（甘味）及び泡立ち抑制効果についても低下する傾向がみられた。（比較例９）
またポリソルベート類は、全てのグレードでうがい薬原液の滴下（希釈操作時）において結晶析出が認められ、また原液の外観、うがい薬（希釈後）の使用感（甘味）、泡立ち抑制効果において低下するグレードが認められた。（比較例１０～１３）
ラウロマクロゴール類は、全てのグレードでうがい薬（希釈後）の低温下の保存において結晶析出があり、また泡立ち抑制効果が低く、うがい薬（希釈後）の使用感（甘味）やうがい薬原液の滴下（希釈操作時）の結晶析出評価にもやや劣る結果となった。（比較例１４及び１５）
ポリオキシエチレンオレイルエーテル類は、使用感が悪いグレードや、うがい薬（希釈後）の低温下の保存において結晶析出が認められるグレードがあった。（比較例１６及び１７）
以上の結果から、うがい薬（希釈後）の使用感（甘味）及び泡立ち抑制効果を損なうことなく、うがい薬原液中の室温における結晶析出（原液の外観）、うがい薬原液の滴下（希釈操作時）の室温における結晶析出抑制（目視）及びうがい薬（希釈後）の液の濁度評価による結晶析出抑制、並びに低温下（５℃）における結晶析出抑制（目視）を満足できる可溶化剤としては、ポリオキシエチレン硬化ヒマシ油類が良好であることがわかった。
In this formulation, crystal precipitation in the gargle solution at room temperature (appearance of the undiluted solution), crystal precipitation during dropping of the gargle solution (during dilution operation), turbidity of the gargle solution (after dilution), and low temperature (5℃) ) For the purpose of suppressing crystal precipitation under (2), the effects of various modifications of surfactants known as solubilizers were evaluated in place of polyoxyethylene hydrogenated castor oils. The usability of the gargle (sweetness after dilution) and foaming suppression (after dilution) were also evaluated.
The polyoxyethylene hydrogenated castor oil, which is the component (D) of the present invention, has a grade in which the effect of suppressing crystal precipitation during dilution operation (dropping of the undiluted solution) and the feeling of use (sweetness) of the gargle (after dilution) are slightly reduced. However, the appearance of the stock solution, the effect of suppressing crystal precipitation (turbidity of the liquid, crystal precipitation at low temperature), and the effect of suppressing foaming were good, and the results were generally satisfactory in all evaluations. (Examples 7 to 10)
When decaglyceryl laurate was used as a solubilizer, crystal precipitation was observed during the dropping of the gargle (during dilution), and the appearance of the undiluted solution became turbid, resulting in poor use (sweet taste) of the gargle (after dilution). ) and the foaming suppression effect also tended to decrease. (Comparative example 9)
In addition, for all grades of polysorbates, crystal precipitation was observed when the gargle concentrate was dropped (during dilution), and the appearance of the concentrate, the feel (sweetness) of the gargle (after dilution), and the foaming suppressing effect were reduced. grade was approved. (Comparative Examples 10 to 13)
All grades of lauromacrogols cause crystal precipitation when gargles (after dilution) are stored at low temperatures, and their foaming suppression effect is low, resulting in poor use (sweetness) of gargles (after dilution) and gargle undiluted solutions. The results were also slightly inferior in the evaluation of crystal precipitation when added dropwise (during dilution operation). (Comparative Examples 14 and 15)
There were some grades of polyoxyethylene oleyl ethers that did not feel good when used, and some grades where crystal precipitation was observed when the gargle (after dilution) was stored at low temperatures. (Comparative Examples 16 and 17)
From the above results, we found that crystal precipitation in the gargle solution at room temperature (appearance of the undiluted solution) and dripping of the gargle solution (during the dilution operation) can be achieved without impairing the feeling of use (sweetness) and foaming suppressing effect of the gargle (after dilution). ) as a solubilizer that satisfies the suppression of crystal precipitation at room temperature (visual observation), the suppression of crystal precipitation by evaluating the turbidity of the gargle (after dilution), and the suppression of crystal precipitation at low temperatures (5°C) (visual observation). , polyoxyethylene hydrogenated castor oils were found to be good.
［うがい薬原液及びうがい薬の調製（４）］
〈実施例１１〉
ポリオキシエチレン硬化ヒマシ油６０ ０．５ｇを加熱して溶解後、プロピレングリコール ５５ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル
０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール １ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム １ｇ及びヒプロメロース９０ＳＨ－４０００ＳＲ ０．１５ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇ及び適量のｐＨ調節剤を加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例１１のうがい薬原液（ｐＨ７．５）を得た（表８）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例１１のうがい薬を得た（表９）。
[Preparation of gargle stock solution and gargle (4)]
<Example 11>
After heating and dissolving 0.5 g of polyoxyethylene hydrogenated castor oil 60, it was dissolved in 55 g of propylene glycol. To this, 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of l-menthol were added and dissolved by stirring at room temperature to form a cetylpyridinium phase.
Next, 1 g of saccharin sodium and 0.15 g of hypromellose 90SH-4000SR were added to 30 g of purified water and dissolved by stirring at room temperature to form a flavoring agent phase.
Add the flavoring agent phase to the cetylpyridinium phase and dissolve by stirring at room temperature, then add and dissolve 0.5 g of sodium azulene sulfonate and an appropriate amount of pH adjuster, and add purified water to bring the total volume to 100 mL. , a gargle stock solution (pH 7.5) of Example 11 was obtained (Table 8).
0.4 mL of the gargle stock solution was diluted with 100 mL of water to obtain the gargle of Example 11 (Table 9).
〈比較例１８〉
グリセリン脂肪酸エステルの配合量を０．０５ｇ及びポリオキシエチレン硬化ヒマシ油６０の配合量を０．１０ｇに変え、セチルピリジニウム相にポリソルベート８０を０．３０ｇ配合したほかは実施例１１と同様にして、比較例１８のうがい薬原液及びうがい薬を得た。
〈比較例１９〉
ポリオキシエチレン硬化ヒマシ油６０の配合量を０．１０ｇに変え、セチルピリジニウム相にポリソルベート８０を０．３０ｇ配合したほかは実施例１１と同様にして、比較例１９のうがい薬原液及びうがい薬を得た。
〈比較例２０〉
セチルピリジニウム相にポリソルベート８０を０．０５ｇ配合したほかは実施例１１と同様にして、比較例２０のうがい薬原液及びうがい薬を得た。
〈比較例２１〉
セチルピリジニウム相にポリソルベート８０を０．１０ｇ配合したほかは実施例１１と同様にして、比較例２１のうがい薬原液及びうがい薬を得た。
〈比較例２２〉
セチルピリジニウム相にポリソルベート８０を０．３０ｇ配合したほかは実施例１１と同様にして、比較例２２のうがい薬原液及びうがい薬を得た。
<Comparative example 18>
Same as Example 11 except that the amount of glycerin fatty acid ester was changed to 0.05 g and the amount of polyoxyethylene hydrogenated castor oil 60 was changed to 0.10 g, and 0.30 g of polysorbate 80 was added to the cetylpyridinium phase. A gargle stock solution and a gargle of Comparative Example 18 were obtained.
<Comparative example 19>
The gargle stock solution and gargle of Comparative Example 19 were prepared in the same manner as in Example 11, except that the amount of polyoxyethylene hydrogenated castor oil 60 was changed to 0.10 g, and 0.30 g of polysorbate 80 was added to the cetylpyridinium phase. Obtained.
<Comparative example 20>
A gargle stock solution and a gargle of Comparative Example 20 were obtained in the same manner as in Example 11, except that 0.05 g of polysorbate 80 was blended into the cetylpyridinium phase.
<Comparative example 21>
A gargle stock solution and a gargle of Comparative Example 21 were obtained in the same manner as in Example 11, except that 0.10 g of polysorbate 80 was blended into the cetylpyridinium phase.
<Comparative example 22>
A gargle stock solution and a gargle of Comparative Example 22 were obtained in the same manner as in Example 11, except that 0.30 g of polysorbate 80 was blended into the cetylpyridinium phase.
実施例１１及び比較例１８～２２で調製したうがい薬原液の処方を表８に、またうがい薬（希釈後）の処方を表９に、夫々示す。 Table 8 shows the prescriptions of the gargle stock solutions prepared in Example 11 and Comparative Examples 18 to 22, and Table 9 shows the prescriptions of the gargles (after dilution).
［試験例１２：原液の希釈操作時の結晶析出評価］
５０ｍＬビーカーに水道水５０ｍＬを入れ、そこに実施例１１及び比較例１８～２２のうがい薬原液を適量滴下した。滴下して５分間放置後、結晶析出の有無を目視にて確認し、下記基準により評価した。
＜原液の希釈操作時の結晶析出 評価基準＞
〇：結晶析出しない
×：結晶析出した
[Test Example 12: Evaluation of crystal precipitation during dilution operation of stock solution]
50 mL of tap water was placed in a 50 mL beaker, and appropriate amounts of the gargle stock solutions of Example 11 and Comparative Examples 18 to 22 were dropped therein. After dropping and leaving for 5 minutes, the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria.
<Evaluation criteria for crystal precipitation during dilution of stock solution>
〇: Crystals did not precipitate ×: Crystals precipitated
［試験例１３：希釈時の濁り評価］
実施例１１及び比較例１８～２２のうがい薬を調製後、紫外可視分光光度計（ＵＶ－１６００、（株）島津製作所）を用いて、波長６６０ｎｍで濁度（ＯＤ６６０）を測定し、下記評価基準にて評価した。
＜希釈時の濁り（濁度：ＯＤ６６０） 評価基準＞
〇：０．０２０以下
△：０．０２０～０．０２５
×：０．０２６以上
[Test Example 13: Evaluation of turbidity during dilution]
After preparing the gargles of Example 11 and Comparative Examples 18 to 22, the turbidity (OD 660 ) was measured at a wavelength of 660 nm using an ultraviolet-visible spectrophotometer (UV-1600, Shimadzu Corporation), and the following results were obtained: Evaluation was made based on the evaluation criteria.
<Evaluation criteria for turbidity during dilution (turbidity: OD 660 )>
〇: 0.020 or less △: 0.020 to 0.025
×: 0.026 or more
［試験例１４：低温保存時（５℃）の結晶析出評価］
実施例１１及び比較例１８～２２のうがい薬（希釈後）を使用し、これを５℃にて７日間保存した後、結晶析出の有無を目視にて確認し、下記基準により評価した。
＜低温保存時の結晶析出評価基準＞
〇：結晶析出しない
×：結晶析出した
[Test Example 14: Evaluation of crystal precipitation during low temperature storage (5°C)]
The gargles (after dilution) of Example 11 and Comparative Examples 18 to 22 were used, and after being stored at 5°C for 7 days, the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria.
<Evaluation criteria for crystal precipitation during low temperature storage>
〇: Crystals did not precipitate ×: Crystals precipitated
また、実施例１１及び比較例１８～２２のうがい薬について、前述の［試験例１：使用感（矯味）］及び［試験例２：泡立ち抑制評価］の手順に従い、うがい薬の使用感（矯味）及び泡立ち抑制について評価した。
これらの結果をあわせて表９に示す。
In addition, the gargles of Example 11 and Comparative Examples 18 to 22 were tested according to the procedures of [Test Example 1: Feeling of Use (Taste Masking)] and [Test Example 2: Foaming Suppression Evaluation]. ) and foaming suppression were evaluated.
These results are shown in Table 9.
表８及び表９に示すように、うがい薬原液においてポリオキシエチレン硬化ヒマシ油６０の配合量を０．１％とし、代わりにポリソルベート８０を０．３０％配合した場合は、グリセリン脂肪酸エステルの配合量を変えても、使用感（矯味）、希釈時の結晶析出、低温保存時の結晶析出及び泡立ちを抑制することは困難であった（比較例１８及び１９）。
またうがい薬原液においてポリオキシエチレン硬化ヒマシ油６０を０．５％に増量した場合（ポリソルベート：０．３０％配合、比較例２２）は、前述の比較例１０と比べて希釈時及び低温保存時の結晶析出抑制に改善がみられたが、使用感（矯味）に欠けたままの結果となり、ポリソルベート８０の配合量が０．１％以下では、使用感（矯味）は改善するものの、希釈時の濁りが生じた（比較例２０及び２１）。また、ポリソルベート８０を０．０５～０．３％の範囲で配合した比較例２０～２２のいずれも、泡立ち抑制がされなかった。以上の結果より、ポリソルベート８０の配合は、特に泡立ち抑制の観点から、少量であっても好ましくないことが確認された。
一方で、グリセリン脂肪酸エステルを０．１％、ポリオキシエチレン硬化ヒマシ油６０
を０．５％配合し、ポリソルベート８０を配合しない実施例１１は、使用感、希釈時の析出、希釈時の濁り、低温保存時の結晶析出及び泡立ち抑制効果に優れていた。
As shown in Tables 8 and 9, when the blending amount of polyoxyethylene hydrogenated castor oil 60 is 0.1% in the gargle stock solution and 0.30% of polysorbate 80 is blended instead, the blending of glycerin fatty acid ester Even if the amount was changed, it was difficult to suppress the feeling of use (flavor masking), crystal precipitation during dilution, crystal precipitation and foaming during low temperature storage (Comparative Examples 18 and 19).
In addition, when the amount of polyoxyethylene hydrogenated castor oil 60 was increased to 0.5% in the gargle stock solution (polysorbate: 0.30% blend, Comparative Example 22), compared to the above-mentioned Comparative Example 10, when diluted and stored at low temperature, Although there was an improvement in the suppression of crystal precipitation, the result was that the feeling of use (taste masking) was still lacking, and when the amount of polysorbate 80 was 0.1% or less, although the feeling of use (taste masking) was improved, when diluted turbidity occurred (Comparative Examples 20 and 21). In addition, foaming was not suppressed in any of Comparative Examples 20 to 22 in which polysorbate 80 was blended in a range of 0.05 to 0.3%. From the above results, it was confirmed that even a small amount of polysorbate 80 is not preferable, especially from the viewpoint of suppressing foaming.
On the other hand, 0.1% glycerin fatty acid ester, 60% polyoxyethylene hydrogenated castor oil
Example 11, which contained 0.5% of polysorbate 80 and did not contain polysorbate 80, had excellent usability, precipitation during dilution, turbidity during dilution, crystal precipitation during low-temperature storage, and foaming suppression effect.
以上の結果から、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩及びｌ－メントールを含有するうがい薬において、（Ａ）特定の矯味剤、（Ｂ）多価アルコール脂肪酸エステル、（Ｃ）セルロース類、（Ｄ）ポリオキシエチレン硬化ヒマシ油類の配合により、うがい薬の使用感、泡立ち抑制、液垂れ抑制及び結晶析出抑制のすべてにおいて満足する効果を得られることが確認された。
そして上記（Ｂ）～（Ｄ）成分を配合し、矯味剤として紹介されている別の化合物を配合した場合にはうがい薬の使用感において満足する結果を得られず、（Ａ）特定の矯味剤を用いない場合には泡立ち抑制効果を全く得られず、（Ａ）特定の矯味剤を用いた場合においても（Ｂ）及び（Ｃ）成分のいずれか若しくは両方を配合しない場合には満足する泡立ち抑制効果を得ることができない結果となり、（Ｃ）成分を未配合とした場合には液垂れ抑制効果を得らない結果となった。そして（Ｄ）成分を未配合とした場合は結晶析出抑制効果を得られず、また、界面活性剤であるラウリン酸デカグリセリルやポリソルベート類、ラウロマウロゴール類、ポリオキシエチレンオレイルエーテル類では結晶析出抑制、泡立ち抑制、使用感（矯味・甘み）のすべてを満足する結果を得ることはできない結果となった。
From the above results, in a gargle containing azulene sulfonic acid and/or its salt, cetylpyridinium and/or its salt, and l-menthol, (A) a specific flavoring agent, (B) polyhydric alcohol fatty acid ester, ( It was confirmed that by blending C) celluloses and (D) polyoxyethylene hydrogenated castor oils, a satisfactory effect can be obtained in terms of the feeling of use of the gargle, suppression of foaming, suppression of dripping, and suppression of crystal precipitation.
When the above components (B) to (D) are combined and another compound introduced as a flavoring agent is added, satisfactory results cannot be obtained in the usability of the gargle; If no agent is used, no foaming suppressing effect can be obtained, and even if (A) a specific flavoring agent is used, it is satisfied if either or both of components (B) and (C) are not blended. The result was that the foaming suppressing effect could not be obtained, and when the component (C) was not blended, the dripping suppressing effect could not be obtained. If component (D) is not added, the effect of suppressing crystal precipitation cannot be obtained, and surfactants such as decaglyceryl laurate, polysorbates, lauromaurogol, and polyoxyethylene oleyl ether cause crystal precipitation. The result was that it was not possible to obtain results that satisfied all of the following: suppression, foaming suppression, and feeling of use (flavor masking/sweetness).
Claims (4)
（Ａ）サッカリンナトリウム及びアセスルファムカリウムから選択される１種以上の矯味剤、
（Ｂ）多価アルコール脂肪酸エステル、
（Ｃ）セルロース類、
（Ｄ）ポリオキシエチレン硬化ヒマシ油類。 In a liquid composition containing azulene sulfonic acid and/or its salt, cetylpyridinium and/or its salt, and l-menthol, the following components (A), (B), (C), and (D) are blended. A mouthwash characterized by:
(A) one or more flavoring agents selected from saccharin sodium and acesulfame potassium;
(B) polyhydric alcohol fatty acid ester,
(C) cellulose,
(D) Polyoxyethylene hydrogenated castor oils.
The (D) polyoxyethylene hydrogenated castor oils include polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene hydrogenated castor oil 100. Mouthwash listed.
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