JP6512614B1 - Oral care agent - Google Patents
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- JP6512614B1 JP6512614B1 JP2017198897A JP2017198897A JP6512614B1 JP 6512614 B1 JP6512614 B1 JP 6512614B1 JP 2017198897 A JP2017198897 A JP 2017198897A JP 2017198897 A JP2017198897 A JP 2017198897A JP 6512614 B1 JP6512614 B1 JP 6512614B1
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- 239000008375 oral care agent Substances 0.000 title claims abstract description 21
- 208000028169 periodontal disease Diseases 0.000 claims abstract description 19
- 208000003265 stomatitis Diseases 0.000 claims abstract description 12
- 239000002158 endotoxin Substances 0.000 claims description 41
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 41
- 241000520272 Pantoea Species 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 2
- 210000004195 gingiva Anatomy 0.000 claims description 2
- 201000001245 periodontitis Diseases 0.000 abstract description 15
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- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 2
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- 102000004127 Cytokines Human genes 0.000 description 1
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- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Cosmetics (AREA)
Abstract
【課題】口腔ケアのターゲットとなる歯周病菌あるいは歯周病菌の影響を効果的に抑制する方法を提供する。【解決手段】口腔ケア剤にLPSを配合することで歯周病を改善できる。LPSは、自然治癒力を高める効果もあることから、LPS配合の口腔ケア剤は、歯周病の改善のほか、抜歯後の歯肉の形成や口内炎等の予防も期待できる。【選択図】図1The present invention provides a method for effectively suppressing the influence of periodontitis bacteria or periodontitis bacteria targeted for oral care. SOLUTION: Periodontal disease can be improved by blending LPS into an oral care agent. Since LPS also has an effect of enhancing the natural healing power, oral care agents with LPS can be expected to prevent gum formation and stomatitis after tooth extraction, as well as improving periodontal disease. [Selected figure] Figure 1
Description
本発明は、口腔内の健康を保つための、リポポリサッカライド(LPS)配合の口腔ケア剤に関する。 The present invention relates to a lipopolysaccharide (LPS) -containing oral care agent for maintaining oral health.
口腔ケアの基本は、口腔内を掃除して清潔にすることにある。口腔内を清潔にすることは、細菌のエサになる食物かすを取り除き、細菌の増殖を防止する。このことは歯周病や虫歯の予防のみならず、体内への細菌の感染を予防する。また歯周病や虫歯がなく健全な歯がそろっていれば、どんな食物も食べることができ、言葉が明瞭に発音でき、また口元にコンプレックスを持たずに笑うことができるので、生活の質を高めることにもつながる。これらのことから近年、特に高齢者に対し口腔ケアが重要視されるようになっている(非特許文献1)。 The basis of oral care is to clean and clean the oral cavity. Cleaning the oral cavity removes food debris that may be a food source of bacteria and prevents bacterial growth. This not only prevents periodontal disease and dental caries, but also prevents bacterial infection in the body. Also, if there is no periodontal disease or tooth decay and healthy teeth are in place, any food can be eaten, words can be pronounced clearly, and because you can laugh without having a complex in your mouth, you can improve the quality of life. It also leads to raising. From these things, in recent years, oral care has been regarded as particularly important for elderly people (Non-Patent Document 1).
口腔内の健康に最も悪影響を与える細菌が歯周病菌(ポルフィロモナス・ジンジバリス菌)である。歯周病菌は偏性嫌気性のグラム陰性細菌で、種々のプロテアーゼや毒性物質を放出して歯周組織を破壊する。莢膜や線毛を有しており、白血球の貪食作用や殺菌作用に抵抗性がある。糖質を代謝できず、主としてアミノ酸やたんぱく質を栄養素とするため、代謝物が悪臭の原因となる。口腔内疾患だけでなくリューマチの発症とも相関があるとされている(非特許文献2)。従って、歯周病菌を抑制することは、口腔ケアにおける必須事項となる。 The bacteria that most adversely affect the health in the oral cavity are periodontitis (porphyromonas gingivalis). Periodontitis is an obligate, anaerobic, gram-negative bacterium that releases various proteases and toxic substances to destroy periodontal tissue. It has a capsule and pilus and is resistant to the phagocytosis and bactericidal action of white blood cells. Metabolites cause malodor because they can not metabolize carbohydrates and mainly contain amino acids and proteins as nutrients. It is believed that there is a correlation not only with intraoral diseases but also with rheumatism (Non-patent Document 2). Therefore, suppressing periodontal disease is an essential item in oral care.
歯周病菌は偏性嫌気性菌であることから、口腔内粘膜表面や歯の表面で生育しているわけではなく、通常の歯磨きで除去することが難しい。一方歯周病菌がグラム陰性細菌であることから、グラム陰性細菌の細胞壁成分であるリポポリサッカライド(LPS)が炎症を誘導することが歯周病の元凶であり、LPSを除去すれば歯周病を抑制できると考え、LPSを除去することを標ぼうする歯磨き粉が販売されている(非特許文献3)。ところが、この菌のLPSは構造が特殊であってLPSレセプターであるTLR4には結合せず、炎症性サイトカインの誘導も顕著に低いのである(非特許文献4)。この点から、歯周病菌の炎症誘導作用は歯周病菌のLPSに負うものではなく、LPSを除去することで歯周病を予防することはできないことがわかる。このように、現状で、歯周病菌あるいは歯周病菌の影響を効果的に抑制する方法は未だ開発されていない。 Since periodontitis is an obligate anaerobe, it does not grow on the surface of the oral cavity mucous membrane or on the surface of teeth, and it is difficult to remove it with ordinary tooth brushing. On the other hand, since periodontal disease bacteria are gram-negative bacteria, induction of inflammation is caused by lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. Toothpaste is marketed, which purports to remove LPS by thinking that it can suppress However, LPS of this bacterium is special in structure and does not bind to TLR4 which is an LPS receptor, and induction of inflammatory cytokines is also significantly low (Non-patent Document 4). From this point, it is understood that the inflammation-inducing action of periodontitis is not due to LPS of periodontitis, and it is not possible to prevent periodontal disease by removing LPS. Thus, at present, methods for effectively suppressing the influence of periodontitis bacteria or periodontitis bacteria have not been developed yet.
口腔ケアのターゲットとなる歯周病菌あるいは歯周病菌の影響を効果的に抑制する方法を提供する。 Provided is a method for effectively suppressing the influence of periodontitis or periodontal disease which is a target of oral care.
歯周病菌はグラム陰性細菌であるが、そのLPSはTLR2に結合するため、本来のLPSとしての自然免疫活性化作用を持っていない(非特許文献4)。このことが、歯周病菌が排除されない理由と考えられる。従って、自然免疫を活性化する作用のある物質を歯磨きあるいは口腔ジェル、チュアブルタブレット等の口腔ケア剤に配合すれば、宿主の持っている免疫力が高まり、歯周病菌が排除できると考えられる。 Periodontitis is a gram-negative bacterium, but since its LPS binds to TLR2, it does not have an innate immune activating action as natural LPS (Non-patent Document 4). This is considered to be the reason why periodontitis is not eliminated. Therefore, it is considered that if a substance having an action to activate innate immunity is blended in a toothpaste or an oral care agent such as an oral gel, a chewable tablet, etc., the immunity possessed by the host can be enhanced and periodontitis bacteria can be eliminated.
ところで、自然免疫を経口で安全に活性化する物質としてパントエア・アグロメランスのLPSが知られている(非特許文献5)。一般にLPSは炎症を誘導し、歯周病を悪化させる原因とされており、LPSを除去することを謳う歯磨きが販売されている(非特許文献3)。しかし発明者らは、パントエア・アグロメランスのLPSを含む口腔ケア剤で口腔内を洗浄することで、歯周病菌の改善がみられることを発見した。 By the way, LPS of Pantoea Agromelans is known as a substance which activates innate immunity safely and orally (nonpatent literature 5). In general, LPS is considered to be a cause of inflammation and exacerbation of periodontal disease, and toothpaste is marketed that toothpaste removes LPS (Non-patent Document 3). However, the inventors discovered that cleaning of the oral cavity with an oral care agent containing LPS from Pantoea agglomerans improved periodontitis bacteria.
このことから、口腔ケア剤にLPSを配合することで歯周病を改善できる。LPSは、自然治癒力を高める効果もあることから、LPS配合の口腔ケア剤は、歯周病の改善のほか、抜歯後の歯肉の形成や口内炎等の予防も期待できる。 From this, periodontal disease can be improved by blending LPS in the oral care agent. Since LPS also has an effect of enhancing the natural healing power, oral care agents with LPS can be expected to prevent gum formation and stomatitis after tooth extraction, as well as improving periodontal disease.
本発明の口腔ケア剤は、パントエア・アグロメランスのリポポリサッカライドを有効成分として含むことを特徴とする。
また、前記口腔ケア剤が、歯周病に対するものであることを特徴とする。
また、前記口腔ケア剤が、術後の歯肉に対するものであることを特徴とする。
また、前記口腔ケア剤が、口内炎に対するものであることを特徴とする。
The oral care agent of the present invention is characterized in that it comprises Pantoea Agromelans lipopolysaccharide as an active ingredient.
In addition, the oral care agent is characterized in that it is for periodontal disease.
Further, the invention is characterized in that the oral care agent is for post-operative gingiva.
In addition, the oral care agent is characterized in that it is for stomatitis.
本発明の口腔ケア剤は、一般的な口腔ケア剤として、特に、歯周病及び口内炎の治療、並びに術後の歯肉ケアに有効である。 The oral care agent of the present invention is effective as a general oral care agent, in particular, in the treatment of periodontal disease and stomatitis, and post-operative gingival care.
[LPS配合口腔用ジェルの製造]
LPS(パントエア・アグロメランス/コムギ粉発酵エキス)配合口腔用ジェルの配合および製造方法を以下に示す。
水にA成分を添加し80℃にて加熱溶解する。これにDを加熱溶解し透明溶液とする。
[Production of LPS-containing oral gel]
The formulation and production method of the oral gel for LPS (pantoea Agromelans / wheat flour fermented extract) combination are shown below.
Add component A to water and heat to dissolve at 80 ° C. Heat and dissolve D in this to make a clear solution.
これを60℃まで冷却後、Bを添加し60℃にて高速攪拌して透明なジェルを調整する。この透明ジェルを攪拌しながら室温まで冷却後、Cを加え攪拌して分散後、さらにEおよびFを添加し、充分に攪拌することで口腔用ジェルを得る。 After cooling this to 60 ° C., add B and stir at 60 ° C. at high speed to prepare a clear gel. After cooling this transparent gel to room temperature while stirring, C is added and stirred to be dispersed, and E and F are further added, and oral gel is obtained by sufficiently stirring.
[LPS配合チュアブルタブレットの製造]
LPS(パントエア・アグロメランス/コムギ粉発酵エキス)配合チュアブルタブレット(500mg/粒)の配合成分を以下に示す。
[Production of LPS-blended chewable tablets]
The components of the chewable tablet (500 mg / grain) blended with LPS (pantoea agromelans / wheat flour extract) are shown below.
※2 EC-12
※ 2 EC-12
[LPS配合口腔用ジェルによる歯周病の改善]
歯科クリニックに通う歯周病患者18名に、実施例1で製造したLPS配合口腔用ジェルを1週間使用してもらい、歯周病の腫れについて5段階(悪化、やや悪化、変化なし、やや改善、改善)での本人評価試験を行った。使用方法は、LPS配合口腔用ジェルを、1日に3回から4回、患部に指先でつけるか、または歯ブラシにつけて患部をブラッシングすることとし、塗布後の洗浄はしないこととした。結果は図1のとおりであった。悪化、やや悪化はゼロで、18人中15人が改善と回答した(図1左)。
[Amelioration of periodontal disease by LPS-containing oral gel]
Eighteen patients with periodontal disease who attend a dental clinic use the LPS-containing oral gel prepared in Example 1 for one week, and have five stages of swelling of periodontal disease (deterioration, slight deterioration, no change, slight improvement) Carried out a personal identification test under The method of use was such that the LPS-containing oral gel was attached to the affected area with a fingertip three to four times a day with a fingertip or put on a toothbrush to brush the affected area, and was not washed after application. The results are as shown in FIG. Deterioration and slight deterioration were zero, and 15 out of 18 persons answered that they improved (Figure 1 left).
別途、LPS非配合口腔用ジェルを、同様の方法で、歯周病患者12人に試してもらった結果、1名が悪化、6名が変化なし、5名がやや改善と回答した(図1右)。 Separately, as a result of having 12 patients with periodontitis try a gel without LPS mixed in the same way, one person deteriorated, 6 persons showed no change, and 5 persons said that they improved slightly (Fig. 1 right).
5段階(悪化、やや悪化、変化なし、やや改善、改善)の評価を、改善なし(悪化、やや悪化、変化なし)と改善あり(やや改善、改善)の二通りに分け、オッズ比をとると、LPS配合口腔用ジェル群のLPS非配合口腔用ジェル群に対する改善のオッズ比は7.00(95%信頼区間:1.29〜37.9)であった。これらの結果から、LPS配合口腔用ジェルに、歯周病改善効果があることが示された。 The odds ratio is divided into five grades (deterioration, slight deterioration, no change, slight improvement, improvement) with no improvement (deterioration, slight deterioration, no change) and improvement (slight improvement, improvement). And, the odds ratio of the improvement to the LPS non-combination oral gel group for the LPS combination oral gel group was 7.00 (95% confidence interval: 1.29 to 37.9). From these results, it was shown that the LPS-containing oral gel has a periodontal disease ameliorating effect.
[LPS配合口腔用ジェルによる抜歯後、根管治療後の歯肉の治癒]
歯科クリニックにて、抜歯を行った患者1名、根管治療後の患者1名に、実施例1で製造したLPS配合口腔用ジェルを1週間使用してもらい、処置後の痛み、腫れ、出血について本人評価試験を行った。使用方法は、LPS配合口腔用ジェルを、1日に3回から4回、患部に指先でつけることとし、塗布後の洗浄はしないこととした。その結果、痛み、改善、腫れとも改善したとの評価であった。図2(写真1)に示されるように、根管治療患者において、試験前には、歯茎に腫れが見られるところ、試験後には腫れがひいていることがわかる。
[Gingival healing after root canal treatment after tooth extraction with LPS-containing oral gel]
At the dental clinic, one patient who had an tooth extraction and one patient after root canal treatment used the LPS-containing oral gel prepared in Example 1 for one week, and after treatment pain, swelling, bleeding Conducted a personal evaluation test. The method of use was that the LPS-containing oral gel was attached to the affected area with a fingertip three to four times a day, and was not washed after application. As a result, it was evaluated that pain, improvement, and swelling were all improved. As shown in FIG. 2 (photograph 1), in the endodontic patients, when swelling is observed in the gums before the test, it can be seen that the swelling is exacerbated after the test.
[LPS配合口腔用ジェルによる口内炎の改善]
歯科クリニックに通う患者のうち、口内炎ができやすい体質の10名に、実施例1で製造したLPS配合口腔用ジェルを1週間使用してもらい、口内炎について5段階(悪化、やや悪化、変化なし、やや改善、改善)での本人評価試験を行った。使用方法は、LPS配合口腔用ジェルを、1日に3回から4回、患部に指先でつけることとし、塗布後の洗浄はしないこととした。結果は図3、図4のとおりであった。ステロイドを使っているという1名に悪化が見られたものの。10名中8名が改善と回答した。また、図3(写真2)に見られるように、義歯との接触による褥瘡性潰瘍では、試験前に見られた歯肉表面のぼつぼつが試験後には消えてなめらかになった。口内炎の場合、通常は医薬品であるケナログ軟膏が処方されるが、ケナログ軟膏では治癒に1週間程度かかるとされている。一方、LPS配合口腔用ジェルでの改善は速く、改善者8名のうち半数が、翌日には治癒したと回答した。10名の口内炎患者の試験結果を集計すると、やや悪化1名、変化なし1名、やや改善2名、改善が6名であった(図4左)。
別途、プラセボ(LPS非配合口腔用ジェル)を、同様の方法で、口内炎患者2人に試してもらった結果、2名とも変化なしと回答した(図4右)。
[Amelioration of stomatitis with LPS-containing oral gel]
Among patients who go to a dental clinic, 10 people with a constitution that can easily cause canker sores use the LPS-containing oral gel prepared in Example 1 for one week, and there are five stages of canker sores (deterioration, slight deterioration, no change, Conducted a personal identification test with a little improvement (improvement). The method of use was that the LPS-containing oral gel was attached to the affected area with a fingertip three to four times a day, and was not washed after application. The results are as shown in FIG. 3 and FIG. Although one person who used a steroid had a deterioration. Eight out of ten answered that they improved. In addition, as seen in FIG. 3 (Photo 2), in the case of decubitus ulcer caused by contact with the denture, the surface roughness of the gum surface observed before the test disappeared and became smooth after the test. In the case of stomatitis, kenalog ointment, which is a medicine, is usually prescribed, but with kenalog ointment, it takes about one week to cure. On the other hand, improvement with LPS-containing oral gel was quick, and half of the eight improvement workers answered that they were healed the next day. When the test results of 10 patients with stomatitis were totaled, 1 was slightly worse, 1 was unchanged, 2 was slightly improved, and 6 was improved (FIG. 4 left).
Separately, as a result of having a placebo (LPS non-formulation oral gel) tested by two patients with stomatitis in the same manner, both of them answered that there was no change (FIG. 4 right).
5段階(悪化、やや悪化、変化なし、やや改善、改善)の評価に対し、それぞれ−2、−1、0、1、2と配点し、それぞれ人数と掛け合わせた数字を総合し、さらに試験人数で割った値は、LPS配合口腔用ジェルは1.3、LPS非配合口腔用ジェルは0となる。プラセボ群の人数が少ないため統計処理はできないものの、これらの結果から、LPS配合口腔用ジェルに、口内炎改善の傾向があることが示された。
For evaluation of 5 levels (deterioration, a little aggravation, no change, a little improvement, amelioration), the points are -2, -1, 0, 1 and 2, respectively, and the numbers are multiplied by the number of people respectively The value divided by the number of people is 1.3 for LPS-containing oral gel and 0 for non-LPS-containing oral gel. Although statistical treatment can not be performed due to the small number of people in the placebo group, these results indicate that the LPS-containing oral gel tends to improve stomatitis.
Claims (4)
An oral care agent characterized by comprising Pantoea Agromelans lipopolysaccharide as an active ingredient.
The oral care agent according to claim 1, wherein the oral care agent is for stomatitis.
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