WO1991002530A1 - Accelerator for periodontal tissue regeneration - Google Patents

Accelerator for periodontal tissue regeneration Download PDF

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Publication number
WO1991002530A1
WO1991002530A1 PCT/JP1990/001066 JP9001066W WO9102530A1 WO 1991002530 A1 WO1991002530 A1 WO 1991002530A1 JP 9001066 W JP9001066 W JP 9001066W WO 9102530 A1 WO9102530 A1 WO 9102530A1
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Prior art keywords
acetyl
periodontal
periodontal tissue
tissue regeneration
accelerator
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PCT/JP1990/001066
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French (fr)
Japanese (ja)
Inventor
Naoki Matsuda
Kyoto Yamazaki
Masahiro Matsuura
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Sunstar Kabushiki Kaisha
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Publication of WO1991002530A1 publication Critical patent/WO1991002530A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms

Definitions

  • the present invention relates to an agent used for regenerating a periodontal membrane destroyed by periodontitis and promoting adhesion between a normal root and connective tissue.
  • periodontitis has been treated mainly by mechanically removing plaque in periodontal pockets by scaling, etc., and in severe cases, by performing periodontal surgical treatment fi.
  • chemotherapy with antibiotics has recently been attempted.
  • these therapies are effective measures to stop the progression of periodontitis, they do not narrowly repair and regenerate broken periodontal tissue, and only improve clinical symptoms. It is due to the self-healing power of the living body.
  • Periodontal tissue is a structure not found in other tissues, in which hard tissue ⁇ (root) and ⁇ tissue (gingiva) adhere to each other through fibrous firm coupling through the periodontal ligament
  • hard tissue ⁇ (root) and ⁇ tissue (gingiva) adhere to each other through fibrous firm coupling through the periodontal ligament
  • epithelial cells on the gingival surface cover the destroyed part before the periodontal ligament regenerates (epidermal downgrowth). Only loose coupling between epithelial tracks and tooth roots occurs. As a result, the restoration and regeneration of the surrounding area is prolonged, and street meat regression occurs frequently.
  • the present invention relates to a periodontal tissue regenerating device having excellent safety, stability and efficacy.
  • the purpose is to provide crude drugs.
  • the present invention relates to N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, N-acetyl-D-mannosamine, and an amino acid obtained by combining these amino sugars with each other.
  • An object of the present invention is to provide a periodontal tissue regenerating agent characterized by containing an N-acetylated amino sugar selected from the group consisting of glycose as an active ingredient.
  • N-acetylated amino sugars are disclosed in Japanese Patent Publication No. 58-119927 as an effective component of an oral composition for inhibiting the adhesion of plaque to teeth.
  • this there is no report that applied this in the treatment of periodontitis.
  • the present inventors have found that these N-acetylated amino sugars also have an effect of promoting periodontal tissue regeneration and are useful for treating periodontitis.
  • N-Acetyl-D-glucosamine used as an active ingredient in the present invention N-acetyl-D-galactosamine is the main component of chondroitin sulfate, which is the main component of chitin, a polysaccharide of the shells of insects and crustaceans, and exists in nature along with N-acetyl-D-mannosamine.
  • the N-acetyl-D-glucosamine oligomer hydrolyzes chitin, neutralizes and desalinates, and is isolated and purified by gel filtration.
  • N-Acetyl-D-galactosamine oligomers are isolated and purified by the gel-pass method after hydrolyzing and acetylating 1,4-polygalactosamine, in which D-galactosamine is mainly 1,4-linked. .
  • cytotoxicity to cultured human periodontal ligament cells is 10; ⁇ 9 / ⁇ ! ⁇ or more, and efficacy is observed between 10 and 1 0 0 / ⁇ ? / ⁇ shows no growth inhibition.
  • the periodontal tissue regeneration-promoting agent of the present invention contains an effective and non-toxic amount of the peracetylated amino sugar in a pharmaceutically acceptable carrier such as a solvent, Combined with tonicity agent, emulsifier, suspending agent, stabilizer To give an external preparation (eg, liquid, emulsion, gel).
  • a pharmaceutically acceptable carrier such as a solvent, Combined with tonicity agent, emulsifier, suspending agent, stabilizer
  • an external preparation eg, liquid, emulsion, gel.
  • Such a periodontal moth regeneration promoter of the present invention can be used by periodontal surgery, or by directly administering it to the ⁇ root after lubrication treatment ⁇ and to the detached gingival surface.
  • the dose can be appropriately determined depending on the condition to be treated and the condition, but usually, the concentration of the N-acetylated amino sugar is 10 to 1009 / lK i .0.01 to 0.01%).
  • the regeneration promoting effect was tested. The results are shown below.
  • Betapaiita tissue ⁇ for dish in periodontal ligament fibroblasts assembly ⁇ 3.0 1 0 4 were seeded ⁇ , after incubation for 1 day at at 37, various ⁇ - Asechi Le of Amino sugar and Origo sugars 1 The mixture was added at a ratio of 0, and further incubated at 37 for 2 days. The cells were then stripped from the petri dish with a 0.15% trypsin solution, and the number of cells was counted using a hemocytometer. As a control, the same test was performed without adding any sample.
  • Table 2 shows the number of cells grown in the Petri dish for each sample.
  • the gingival flap was repositioned, and suture and back protection was applied for one week.
  • the test site was sampled, a tissue specimen was prepared by a conventional method, and an eyepiece microphone was placed under a microscope.
  • the distance between each part was also measured using a mouthpiece and quantified according to the following criteria.
  • Table 3 shows the length of bone removal ⁇ 10 ⁇ .
  • N-acetyl-D-galactosamin and its trimer, N-acetyl-D-mannosamine, and N-acetyl-D-glucosamino trimer slightly inhibit epithelial downgrowth and also reduce On the other hand, it clearly showed a promoting effect on the fibrous adhesion rate.
  • N-acetylated amino sugars and oligosaccharides have excellent periodontal tissue regeneration promoting action.

Abstract

An accelerator for periodontal tissue regeneration comprising as the active ingredient an N-acetylated amino sugar selected from the group consisting of N-acetyl-D-glucosamine, N-acetly-D-galactosamine, N-acetyl-D-mannosamine, and oligosaccharides comprising the above amines linked α-1,4 or β-1,4.

Description

明 細 畲 発明の分野  Description 分野 Field of the Invention
本発明は、 歯周炎により破壊ざれた歯拫膜を再生し、 正常な歯根 と結合組織間の付着も促進するために用いる薬剤に関する。  The present invention relates to an agent used for regenerating a periodontal membrane destroyed by periodontitis and promoting adhesion between a normal root and connective tissue.
従来の技術  Conventional technology
従来、 歯周炎の治療方法としては、 主としてスケーリ ング等によ る機械的な歯周ポケッ ト内のプラーク除去が行なわれ、 また重篤な 場合には歯周外科的処 fiが行なわれ、 加えて最近では抗生物質によ る化学療法も試みられている。 しかし、 これらの療法は、 歯周炎の 進行を阻止するには有効な方策であるが、 玻壊された歯周組織を狭 極的に修復、 再生させるものではなく、 臨床症状の改善はあくまで 生体の自己治癒力によるものである。  Conventionally, periodontitis has been treated mainly by mechanically removing plaque in periodontal pockets by scaling, etc., and in severe cases, by performing periodontal surgical treatment fi. In addition, chemotherapy with antibiotics has recently been attempted. However, although these therapies are effective measures to stop the progression of periodontitis, they do not narrowly repair and regenerate broken periodontal tissue, and only improve clinical symptoms. It is due to the self-healing power of the living body.
歯周組織は硬組锇（歯根）と钦組織（歯肉）とが歯根膜を介した線維 性の強固な桔合により付着するという、 他の組織に見られない構造 を有しているが、 歯周炎により歯周組織が破壊されると、 歯根膜が 再生する前に歯肉表面の上皮細胞が破壊部分を被覆してしまう（上 皮のダウングロース）ために、 上皮組轍と歯根との緩い桔合しか生 じない。 このため ¾周耝繳の修復、 再生が連延し、 街肉の退縮が高 頻度に生じる。 これに対し、 正常な線維性結合を達成するために、 従来から、 （1 )クェン酸による根面処理（2 )細胞付着性糖タンパク であるフィブロネクチンの局所への適用（3 )生体適合性の高い遮断 膜により上皮のダウングロースを抑制する锈導組織再生法（G T R 法）が知られているが、 （1 )は細胞に対する為害性、 （2 )は高分子 であるフイブロネクチンの安定性、 抗原性、 （3 )は摘出のための再 手術の必要性および術者による差といった問題点を抱えており、 安 全性、 剤型化の容易性、 有効性を兼ね備えた歯周組織再生を促進す る薬剤の開発が望まれている。 Periodontal tissue is a structure not found in other tissues, in which hard tissue 锇 (root) and 钦 tissue (gingiva) adhere to each other through fibrous firm coupling through the periodontal ligament However, if periodontal tissue is destroyed by periodontitis, epithelial cells on the gingival surface cover the destroyed part before the periodontal ligament regenerates (epidermal downgrowth). Only loose coupling between epithelial tracks and tooth roots occurs. As a result, the restoration and regeneration of the surrounding area is prolonged, and street meat regression occurs frequently. On the other hand, in order to achieve a normal fibrous connection, (1) root surface treatment with citric acid (2) local application of fibronectin, a cell-adhesive glycoprotein, (3) biocompatibility There is a known method of conducting tissue regeneration (GTR method) that suppresses epithelial downgrowth by using a high barrier membrane. (1) is harmful to cells, (2) is the stability of fibronectin, a macromolecule, antigen (3) has problems such as necessity of re-operation for extirpation and differences among operators, and promotes periodontal tissue regeneration that combines safety, ease of formulation, and effectiveness The development of more drugs is desired.
発明の目的  Purpose of the invention
本発明は、 前記安全性、 安定性および有効性に優れた歯周組織再 生剤を提供することを目的とする。 The present invention relates to a periodontal tissue regenerating device having excellent safety, stability and efficacy. The purpose is to provide crude drugs.
発明の概要  Summary of the Invention
本発明は、 N—ァセチルー D—グルコサミ ン、 N—ァセチルー D 一ガラク トサミ ン、 N—ァセチルー D—マンノサミ ンおょぴこれら のアミ ノ糖がな一または /6— 1 , 4桔合したオリ ゴ糖からなる群か ら選ばれる N—ァセチル化ァミノ糖を活性成分として含有すること を特撳とする歯周組繳再生剤を提供するものである。  The present invention relates to N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, N-acetyl-D-mannosamine, and an amino acid obtained by combining these amino sugars with each other. An object of the present invention is to provide a periodontal tissue regenerating agent characterized by containing an N-acetylated amino sugar selected from the group consisting of glycose as an active ingredient.
これらの N—ァセチル化ァミノ糖は特公昭 5 8— 1 1 9 2 7号に おいて、 本出願人が歯垢の歯牙への付着抑制口腔用組成物の有効成 分として開示しているが、 歯周炎の治療においてこれを応用した報 告はない。 ところが、 意外にも、 本発明者らは、 これらの N—ァセ チル化ァミノ糖が歯周組織再生促進効果も有し、 歯周炎の治療に有 用であることを見出した。  These N-acetylated amino sugars are disclosed in Japanese Patent Publication No. 58-119927 as an effective component of an oral composition for inhibiting the adhesion of plaque to teeth. However, there is no report that applied this in the treatment of periodontitis. However, surprisingly, the present inventors have found that these N-acetylated amino sugars also have an effect of promoting periodontal tissue regeneration and are useful for treating periodontitis.
発明の詳細な説明  Detailed description of the invention
本発明で活性成分として用いる N—ァセチルー D—グルコサミ ン は昆虫や甲殻類の殻の多糖であるキチンの主成分、 N—ァセチル— D—ガラク トサミ ンはコンドロイチン硫酸の主成分であり、 N—ァ セチルー D—マンノサミ ンとともに自然界に存在する。 また、 N - ァセチルー D—グルコサミ ンオリゴマーはキチンを加水分解し、 中 和、 脱塩の後、 ゲル · 過法によって単離精製される。 N—ァセチル 一 D—ガラク トサミ ンオリゴマーは D—ガラク トサミ ンが主に 一 1 , 4結合したな一 1 , 4ポリガラク トサミ ンを加水分解、 ァセチル 化後、 ゲル通過法によって単離精製される。 N-Acetyl-D-glucosamine used as an active ingredient in the present invention N-acetyl-D-galactosamine is the main component of chondroitin sulfate, which is the main component of chitin, a polysaccharide of the shells of insects and crustaceans, and exists in nature along with N-acetyl-D-mannosamine. The N-acetyl-D-glucosamine oligomer hydrolyzes chitin, neutralizes and desalinates, and is isolated and purified by gel filtration. N-Acetyl-D-galactosamine oligomers are isolated and purified by the gel-pass method after hydrolyzing and acetylating 1,4-polygalactosamine, in which D-galactosamine is mainly 1,4-linked. .
これらの物質は生体由来物質であり非常に安全性が高く、 例えば 培養したヒ ト歯根膜細胞に対する細胞毒性は 1 0 ;κ9/ί!β以上であり、 有効性の観察される 1 0〜 1 0 0 /ί ?/ιτβでは增殖阻害は全く見ら れない。  These substances are of biological origin and have very high safety.For example, cytotoxicity to cultured human periodontal ligament cells is 10; κ9 / ί! Β or more, and efficacy is observed between 10 and 1 0 0 / ί? / Ιτβ shows no growth inhibition.
かく して、 本発明の歯周組織再生促進剤は、 通常の製剤技術に従つ て、 有効かつ非毒性量の該 Ν—ァセチル化ァミ ノ糖を医薬上許容さ れる担体、 例えば溶剤、 等張化剤、 乳化剤、 懸闺剤、 安定化剤と合 して外用剤（例えば、 液剤、.乳液、 ゲル剤）とすることができる。 か かる本発明の歯周組蛾再生促進剤は歯周外科処置、 あるいは拫面滑 沢処理後の歯根靣および剥離歯肉面に直接投与することにより使用 できる。 投与量は治療すべき症状、 郞位により適宜增弒できるが、 通常、 該 N—ァセチル化ァミ ノ糖を 1 0〜 1 0 0 9/ lK i .0 0 1 - 0.0 1 %)の濃度で 1回 0. 1〜 0.3 程度、 1 日 1〜 3回患 郞に塗布、 あるいは注入により適用すると、 所望の歯周組蛾再生促 進効果が発揮される。 Thus, the periodontal tissue regeneration-promoting agent of the present invention contains an effective and non-toxic amount of the peracetylated amino sugar in a pharmaceutically acceptable carrier such as a solvent, Combined with tonicity agent, emulsifier, suspending agent, stabilizer To give an external preparation (eg, liquid, emulsion, gel). Such a periodontal moth regeneration promoter of the present invention can be used by periodontal surgery, or by directly administering it to the {root after lubrication treatment} and to the detached gingival surface. The dose can be appropriately determined depending on the condition to be treated and the condition, but usually, the concentration of the N-acetylated amino sugar is 10 to 1009 / lK i .0.01 to 0.01%). When applied to a patient about 0.1 to 0.3 times, once to three times a day, or by injection, the desired periodontal moth regeneration promoting effect is exhibited.
つぎに実施例を挙げて本発明をさらに詳しく鋭明する。  Next, the present invention will be described in more detail with reference to examples.
実施例 1  Example 1
成分 量 Ingredient Amount
Ν—ァセチルー D—マンノサミ ン 0.0 0 2Ν-acetyl-D-mannosamine 0.0 0 2
(シグマ社製） (Manufactured by Sigma)
生理食塩水 全量 1 0 0?に绸整 これらの成分を混合溶解し、 無菌濾過して液剤を得る。 実施例 2 Adjust the total amount of physiological saline to 100 ?. These components are mixed and dissolved, and aseptically filtered to obtain a liquid preparation. Example 2
成分 量 Ingredient Amount
N—ァセチルー D—ガラク トサミ ノ 0.0 1 ? ダイマ ー（フナュシ薬品） N-acetyl-D-galactosamino 0.0 1? Dimer (Funashi Chemical)
ステアリ ン酸 29 セタノール 0.5? ラノ リ ン 2? イソブ口ピルミ リステート 29 スクヮラン S9 流動パラフィ ン Stearyl acid 29 Cetanol 0.5? Lanolin 2? Isobu mouth Pirmi restate 29 Squalane S9 Liquid paraffin
ポリオキシエチレンセチルエーテル 1 .7? トリエタノ一ルァミ ン 19 グリセリン 49 防腐剤 適量 精製水 全量〖 0 0 こ調整 れらの成分を用い、 常法に従って乳液を得る Polyoxyethylene cetyl ether 1.7? Triethanolamine 19 Glycerin 49 Preservatives Appropriate amount Purified water Total amount 0 0 Adjust Use these ingredients to obtain an emulsion according to the usual method
実施例 3  Example 3
成分 量 Ingredient Amount
N—ァセチル— D—グルコサミ ノ トライマー 0 . 0 1 s ラウ リル硫酸ナ ト リ ウム 0 . 2 9 カルボキシメチルセルロース 2 9 グリセリン 4 0 9 精製水 全量 1 0 0 9に绸整 これらの成分を混合し、 ゲル剤を得る N-Acetyl-D-Glucosamino Trimer 0.01 s Sodium lauryl sulfate 0.29 Carboxymethylcellulose 29 Glycerin 409 Purified water Adjust to a total volume of 100 9 Get a gel
N—ァセチルー D—グルコサミ ン、 N—ァセチルー D—ガラク ト サミ ン、 N—ァセチルー D—マンノサミ ンおよぴこれらのアミ ノ糖 がな一または ー 1 . 4桔合によるオリゴ糖の歯周組織再生促進作 用を試験した。 以下にその桔果を示す,  N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, N-acetyl-D-mannosamine and the periodontal tissue of oligosaccharides obtained by combining these amino sugars with or without 1.4 The regeneration promoting effect was tested. The results are shown below.
に対する作用  Action on
ヒ ト抜去歯に残存する歯根膜より歯根膜線維芽細胞を、 歯肉組織 より上皮細胞を初代培養し、 各種 N—ァセチル化ァミノ糖およびォ リゴ糖を有する歯根膜線維芽細胞および齒肉上皮細胞への走化性活 性を、 孔径 8 ミ クロ ンのフィルターを用いた 4 8穴マイクロチャ ン パー法により測定した。 Periodontal ligament fibroblasts from the periodontal ligament remaining in the human extracted tooth Primary epithelial cells were further cultured, and the chemotactic activity on periodontal ligament fibroblasts and gingival epithelial cells having various N-acetylated amino and oligosaccharides was examined using a filter with a pore size of 8 micron. It was measured by the 48-hole micro-champering method.
5 . 0 X 1 0 6個/ *βの細胞懸闺液をチヤンパ一の上室に、 下室に は各種の Ν—ァセチル化ァミノ糖およびォリゴ糖を 1 0〜 1 0 0 # 9 ^2の割合で加え、 3 7でで 4時間インキュベートした。 ついで フィルタ一を固定し、 ディフークイック（D i ff— Q ui ck)染色後、 フィルターの底部まで遊走した钿跑数を顕漱鎗下で計数した。 対照 として、 検体を加えずに同様に試験を行なった。 対照の係数値を 1 0 0 %とした場合の N—ァセチル化ァミノ糖およびォリゴ糖添加時 の相対的割合を第 1表に示す。 5.0 X 10 6 cells / * β cell suspension in the upper chamber of the chamber, and in the lower chamber various acetylated amino and oligosaccharides of 10 to 100 # 9 ^ 2 And incubated at 37 for 4 hours. Then, the filter was fixed, and after Diff-Quick staining, the number of cells that migrated to the bottom of the filter was counted under a microscope. As a control, the same test was performed without any sample. Table 1 shows the relative ratios when the N-acetylated amino sugar and the oligosaccharide were added when the coefficient value of the control was 100%.
第 1表 Table 1
Figure imgf000011_0001
Figure imgf000011_0001
第 1表に示すごとく、 Ν—ァセチルー D—グルコサミ ンとそのダ イマ一、 トライマ-、 Ν—ァセチルー D—ガラク トサミ ンとそのダ イマ一、 トライマ-、 さらに Ν—ァセチルー D—マンノサミ ンは、 いずれもが歯根膜線維芽細胞に対する特異的な走化性活性を有し、 歯肉上皮钿胞にはほとんど作用しなかった。 この結果、 明らかに、 これらの薬剤は歯周組截再生の中心となる歯根胰線維芽細胞のみを より選択的に病変部位に遊走せしめる作用を有する。 As shown in Table 1, Ν-acetyl-D-glucosamine and its dimer, trimer, Ν-acetyl-D-galactosamine and its dimer, trimer, and Ν-acetyl-D-mannosamine All had specific chemotactic activity on periodontal ligament fibroblasts and had little effect on gingival epithelial cells. As a result, apparently, these drugs have an action of selectively migrating only the root fibroblasts, which are the center of periodontal regeneration, to the lesion site.
( 2 )齒根膜線維芽細胞の増殖性に対する作用  (2) Effect on proliferation of periodontal ligament fibroblasts
各種 N -ァセチル化アミノ糖およびオリゴ糖の歯根膜線維芽細胞 の增殖性に対する作用を測定した。  The effects of various N-acetylated amino sugars and oligosaccharides on the proliferation of periodontal ligament fibroblasts were measured.
直径 3 5 βπηの組織培奖用シャーレに歯根膜線維芽組截 3 . 0 1 0 4饀を播種し、 3 7でで 1 日インキュベート後、 各種 Ν—ァセチ ル化ァミノ糖およびォリゴ糖を 1 0 0 の割合で加え、 さら に 3 7てで 2日インキュベー トした。 ついで钿胞を 0 . 1 5 %トリ ブシン溶液でシャーレより剥雌し、 钿胞数を血球計算盤により計測 した。 対照として、 検体を加えずに同様に試験を行なった。 Diameter 3 5 Betapaiita tissue培奖for dish in periodontal ligament fibroblasts assembly截3.0 1 0 4 were seeded饀, after incubation for 1 day at at 37, various Ν- Asechi Le of Amino sugar and Origo sugars 1 The mixture was added at a ratio of 0, and further incubated at 37 for 2 days. The cells were then stripped from the petri dish with a 0.15% trypsin solution, and the number of cells was counted using a hemocytometer. As a control, the same test was performed without adding any sample.
各検体においてシャーレ中で増殖した細胞数を第 2表に示す。 第 2表 Table 2 shows the number of cells grown in the Petri dish for each sample. Table 2
検 体 細胞数/シャーレ 対 照 1 . 1 X 1 0 Specimen cell count / Petri dish control 1.1 X 10
N—ァセチルー D—グルコサミ ン 1 .3 X 1 0 N-acetyl-D-glucosamine 1.3 X 10
N—ァセチルー D—ガラク トサミ ン 1 .6 X 1 0 N-acetyl-D-galactosamin 1.6 X 10
N—ァセチルー D—マンノサミ ン 1 .8 X 1 0 N—Acetylous D—Mannosamine 1.8 X 10
N—ァセチルー D—グルコサミ ノ 1 .2 1 0 N-acetyl-D-glucosamino 1.2 1 0
ダイマー Dimer
N—ァセチルー D—グルコサミノ 1 .2 X 1 0  N—Acetyl D—Glucosamino 1.2 X 10
トライマ-Trimmer-
N—ァセチルー D—ガラク トサミ ノ ! 1 .7 X 1 0 * ダイマ一 N—Acetylous D—Galactosamino ! 1.7 X 10 *
N—ァセチル— D—ガラク トサミ ノ 1.9 X 1 0  N—Acetyl—D—Galactosamino 1.9 X 10
トライマ- 第 2表に示すごとく、 N—ァセチルー D-グルコサミ ンとそのダ イマ一、 トライマ-、 N—ァセチルー D—ガラク トサミ ンとそのダ イマ一、 トライマ-、 さ らに N—ァセチルー D—マンノ サミ ンは、 いずれもが歯根胰線維芽細胞の增殖性を高めた。 Trimer-As shown in Table 2, N-acetyl-D-glucosamine and its Ima-I, Trimer-, N-Acetyl-D-Galactosamin and its Dima-, Trimer-, and N-Acetyl-D-Mannosamin all enhanced root-fibroblast proliferation. .
( 3 )ィヌ歯肉剥離搔爬手術後の歯周組織再生適程に対する作用 ィヌ歯肉剥離搔爬手術後の歯周組敏再生過程に対する各種 N—ァ セチル化アミノ糖およびオリゴ糖の作用を病理組截学的定量評価法 により検討した。 ブラヅ シング等により健常な歯周組織を確立した 上下額小臼歯部に、 常法に従って歯肉剥離搽 ^手術を施した。 この 際、 後の病理組織学的定量化の基準点とするため、 歯槽骨の削除を 実施する前後で、 根面にノ ツチと呼ばれる基準点を付与した。 検体 は実施例 3で示したと同様なゲル剤とし、 左 上下額の露出した根 面上に 1部位当り 5 O il?を投与し、 対照として右側上下額には薬物 を配合しないゲル剤を投与した。 手術後は歯肉弁を復位し、 縫合と バックによる保護を 1週間施した。 評価は術後 4週目に被検部位を 採取し、 常法により組織標本を作成した後、 顕微镜下で接眼マイク - - (3) Effects of various N-acetylated amino and oligosaccharides on periodontal tissue regeneration after dog gingival exfoliation and reptomy surgery The study was carried out by a truncated quantitative evaluation method. The gingival exfoliation was performed on the upper and lower premolars where healthy periodontal tissue was established by brushing or the like according to a conventional method. At this time, a reference point called a notch was added to the root surface before and after the removal of the alveolar bone to serve as a reference point for later histopathological quantification. The sample was the same gel as shown in Example 3, and 5 Oil? Was administered per site on the exposed root surface of the left and right forehead, and a gel without drug was administered to the right and left forehead as a control. did. After the operation, the gingival flap was repositioned, and suture and back protection was applied for one week. Four weeks after surgery, the test site was sampled, a tissue specimen was prepared by a conventional method, and an eyepiece microphone was placed under a microscope. --
口メ一夕一を用いて各部位間の距離も測定し、 以下の基準で定量化 した。 The distance between each part was also measured using a mouthpiece and quantified according to the following criteria.
1 ： 上皮のダウングロース率（％) 骨削除前のノ ツチ下緣から上皮 1: Epithelial downgrowth rate (%) Epithelium from Notchi under 骨 before bone removal
の最根尖側までの距離 .  The distance to the apical side of.
骨削除の長さ ハ A u U Bone removal length c A u U
2： 線維性付着率（％) 線維が垂直おょぴ斜走する部分の萇さ ν 1 Λ η 2: Fibrous attachment rate (%) The judgeness of the part where the fiber runs obliquely vertically ν 1 Λ η
骨削除の長さ Χ 1 0 ϋ 結果を第 3表に示す。 Table 3 shows the length of bone removal {10} .
第 3表 Table 3
Figure imgf000016_0001
Figure imgf000016_0001
第 3表に示すごとく、 N—ァセチルー D—ガラク トサミ ンとその トライマー、 N—ァセチルー D—マンノサミ ン、 さらに N—ァセチ ルー D—グルコサミノ トライマーは、 上皮のダウングロースをわず かに抑制するとともに、 锿維性付着率に対しては明らかに促進作用 を示した。  As shown in Table 3, N-acetyl-D-galactosamin and its trimer, N-acetyl-D-mannosamine, and N-acetyl-D-glucosamino trimer slightly inhibit epithelial downgrowth and also reduce On the other hand, it clearly showed a promoting effect on the fibrous adhesion rate.
以上の桔果から明らかなごとく、 N—ァセチル化ァミノ糖および オリゴ糖はすぐれた歯周組織再生促進作用を有する。  As is clear from the above results, N-acetylated amino sugars and oligosaccharides have excellent periodontal tissue regeneration promoting action.

Claims

請求の範囲 . The scope of the claims .
1 . N—ァセチルー D—グルコサミ ン、 N—ァセチルー D—ガラ ク トサミ ン、 N—ァセチルー D—マンノサミ ンおよびこれらが 一 または — 1 , 4—結合したオリゴ糖からなる群から選ばれる N— ァセチル化ァミノ糖を活性成分として含有することを特徵とする歯 周組織再生促進剤。- 1. N-Acetyl selected from the group consisting of N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, N-acetyl-D-mannosamine, and oligosaccharides in which these are mono- or mono-, 1,4-linked A periodontal tissue regeneration promoter comprising a functionalized amino sugar as an active ingredient. -
2. 該 N—ァセチル化ァミノ糖を 0.0 0 1〜 0.0 1 %含有する 2. Contains 0.001 to 0.01% of the N-acetylated amino sugar
3. 外用剤である蹐求項 1記載の歯周組敏再生促進剤。 3. The periodontal sensitization regeneration promoter according to claim 1, which is an external preparation.
PCT/JP1990/001066 1989-08-25 1990-08-22 Accelerator for periodontal tissue regeneration WO1991002530A1 (en)

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