JPH0383927A - Periodontal tissue regeneration promoter - Google Patents
Periodontal tissue regeneration promoterInfo
- Publication number
- JPH0383927A JPH0383927A JP1220031A JP22003189A JPH0383927A JP H0383927 A JPH0383927 A JP H0383927A JP 1220031 A JP1220031 A JP 1220031A JP 22003189 A JP22003189 A JP 22003189A JP H0383927 A JPH0383927 A JP H0383927A
- Authority
- JP
- Japan
- Prior art keywords
- acetyl
- periodontal
- tissue regeneration
- active ingredient
- periodontal tissue
- 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
- 230000003239 periodontal effect Effects 0.000 title claims description 22
- 230000017423 tissue regeneration Effects 0.000 title claims description 17
- 150000002337 glycosamines Chemical class 0.000 claims abstract description 17
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 10
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 10
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims abstract description 8
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims abstract description 8
- 229950006780 n-acetylglucosamine Drugs 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- OVRNDRQMDRJTHS-ZTVVOAFPSA-N N-acetyl-D-mannosamine Chemical compound CC(=O)N[C@@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-ZTVVOAFPSA-N 0.000 claims abstract description 6
- 210000002379 periodontal ligament Anatomy 0.000 abstract description 12
- 201000001245 periodontitis Diseases 0.000 abstract description 9
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 abstract description 7
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 abstract description 7
- 230000001737 promoting effect Effects 0.000 abstract description 6
- 210000002808 connective tissue Anatomy 0.000 abstract description 2
- 239000007924 injection Substances 0.000 abstract description 2
- 238000002347 injection Methods 0.000 abstract description 2
- 230000001172 regenerating effect Effects 0.000 abstract description 2
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 210000004746 tooth root Anatomy 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 8
- 210000002950 fibroblast Anatomy 0.000 description 6
- 238000001356 surgical procedure Methods 0.000 description 6
- 239000000539 dimer Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000013638 trimer Substances 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 2
- 229920002101 Chitin Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 238000005299 abrasion Methods 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- 230000003399 chemotactic effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 210000001648 gingival epithelial cell Anatomy 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-CBPJZXOFSA-N 2-amino-2-deoxy-D-mannopyranose Chemical compound N[C@@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-CBPJZXOFSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 208000002064 Dental Plaque Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 208000005888 Periodontal Pocket Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- -1 Polyoxyethylene Polymers 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000004763 bicuspid Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000004956 cell adhesive effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 201000005562 gingival recession Diseases 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011158 quantitative evaluation Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
Classifications
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、歯周炎により破壊された歯根膜を再生し、正
常な歯根と結合組織間の付着を促進するために用いる薬
剤に関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a drug used to regenerate periodontal ligaments destroyed by periodontitis and to promote attachment between normal tooth roots and connective tissues.
粱朱！蓋貨
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置が行なわれ
、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、破壊された歯周組織を積極
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。Ruizhu! Traditionally, periodontitis has been treated by mechanically removing plaque from periodontal pockets, mainly through scaling, and in severe cases, periodontal surgery. Chemotherapy with antibiotics has also been tried. However, although these therapies are effective measures to prevent the progression of periodontitis, they do not actively repair or regenerate the destroyed periodontal tissue, and the improvement of clinical symptoms is limited to the biological system. This is due to self-healing ability.
発明が解決しようとする課題
歯周組織は硬組織＜ｔｎ根）と軟組織（歯肉）が歯根膜
を介した線維性の強固な結合により付着するという他の
組織には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、上皮組織と歯根との緩い結合しか
生じない。このため歯周組織の修復、再生が遅延し、歯
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）クエン酸によ
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誘導組織再生法
（ＧＴＲ法）が知られているが、（１）は細胞に対する
為害性、（２）は高分子であるフィ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。Problems to be Solved by the Invention Periodontal tissue has a structure that is not found in other tissues, in which hard tissue < tn roots) and soft tissue (gingiva) are attached to each other through strong fibrous bonds via the periodontal ligament. However, when the periodontal tissue is destroyed due to periodontitis, the epithelial cells on the gingival surface cover the destroyed area before the periodontal ligament regenerates (epithelial downgrowth), which causes the epithelial tissue and the tooth root to deteriorate. Only a loose connection occurs. As a result, periodontal tissue repair and regeneration are delayed, and gingival recession occurs frequently. On the other hand, in order to achieve normal fibrous connections, conventional methods have been used: (1) root surface treatment with citric acid, (2) local application of fibronectin, a cell-adhesive glycoprotein, and (3) biocompatible A guided tissue regeneration method (GTR method) that suppresses epithelial downgrowth using a high barrier membrane is known, but (1) is harmful to cells, and (2) is a polymeric fibronectin that has stability and antigenicity. , (3) has problems such as the need for reoperation for removal and differences depending on the surgeon, and safety,
It is desired to develop a drug that promotes periodontal tissue regeneration that is both easy to formulate and effective.
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。An object of the present invention is to provide a periodontal tissue regenerating agent having excellent safety, stability, and effectiveness.
課題を解決するための手段
Ｎ−アセチル−Ｄ−グルコサミン、Ｎ−アセチル−Ｄ−
ガラクトサミン、Ｎ−アセチル−Ｄ−マンノサミンおよ
びこれらのアミノ糖がα−またはβ−１，４結合したオ
リゴ糖からなる群から選ばれるＮ−アセチル化アミノ糖
を活性成分として含有することを特徴とする歯周組織再
生剤を提供するものである。Means for solving the problem N-acetyl-D-glucosamine, N-acetyl-D-
It is characterized by containing as an active ingredient an N-acetylated amino sugar selected from the group consisting of galactosamine, N-acetyl-D-mannosamine, and oligosaccharides in which these amino sugars are α- or β-1,4 linked. The present invention provides a periodontal tissue regeneration agent.
これらのＮ−アセチル化アミノ糖は特公昭５８−１１９
２７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−アセチル化アミノ
糖が歯周組織再生促進効果を有し、歯周炎の治療に有用
であることを見出した。These N-acetylated amino sugars were disclosed in Japanese Patent Publication No. 58-119
No. 27, the present applicant discloses it as an active ingredient of an oral composition for suppressing the adhesion of dental plaque to teeth, but there is no report on its application in the treatment of periodontitis. However, the present inventors unexpectedly discovered that these N-acetylated amino sugars have the effect of promoting periodontal tissue regeneration and are useful for the treatment of periodontitis.
本発明で活性成分として用いるＮ−アセチル−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−アセチル−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−アセチル−Ｄ−マンノサミ
ンとともに自然界に存在する。また、Ｎ−アセチル−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、ゲル濾過法によって単離精製される。Ｎ−
アセチルー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α−１，４結合したα−ｌ。N-acetyl-D-glucosamine used as an active ingredient in the present invention is the main component of chitin, which is a polysaccharide found in the shells of insects and crustaceans, and N-acetyl-D-galactosamine is the main component of chondroitin sulfate. It occurs in nature along with D-mannosamine. Also, N-acetyl-D
- Glucosamine oligomers are isolated and purified by gel filtration after hydrolyzing chitin, neutralizing and desalting. N-
Acetyl-D-galactosamine oligomer is α-l, in which D-galactosamine is mainly linked with α-1,4 bonds.
４ポリガラクトサミンを加水分解、アセチル化後、ゲル
濾過法によって単離精製される。After hydrolyzing and acetylating 4-polygalactosamine, it is isolated and purified by gel filtration.
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叩／−以上であり、有効性の観察されるｌＯ〜１００
μｇ／−では増殖阻害は全く見られない。These substances are biologically derived substances and are extremely safe; for example, their cytotoxicity to cultured human periodontal ligament cells is 1.
0 beats/- or more, and the observed effectiveness is 10~100
No growth inhibition was observed at μg/−.
かくして、本発明の歯周組織再生促進剤は、通常の製剤
技術に従って、有効かつ非毒性量の該Ｎアセチル化アミ
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、懸濁剤、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
の歯周組織再生促進剤は歯周外科処置、あるいは根面滑
沢処理後の歯根面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、部位によ
り適宜増減できるが、通常、該Ｎ−アセチル化アミノ糖
を１０〜１００ μｇ／ａ１２（０，０Ｏ１〜０．０１
％）の濃度で１回０．ｌ〜０．３ｉ＋１２程度、１日１
〜３回患部に塗布、あるいは注入により適用すると、所
望の歯周組織再生促進効果が発揮される。Thus, the periodontal tissue regeneration promoter of the present invention can be prepared by combining an effective and non-toxic amount of the N-acetylated amino sugar with a pharmaceutically acceptable carrier such as a solvent, a tonicity agent,
It can be combined with emulsifiers, suspending agents, and stabilizers to form preparations for external use (for example, solutions, emulsions, and gels). The periodontal tissue regeneration promoting agent of the present invention can be used in periodontal surgery or by directly administering to the tooth root surface and avulsed gingival surface after root surface lubricating treatment. The dosage can be increased or decreased as appropriate depending on the symptoms and site to be treated, but usually the N-acetylated amino sugar is 10 to 100 μg/a12 (0.0O1 to 0.01
%) once at a concentration of 0. l~0.3i+12 degree, 1 day
When applied to the affected area three times or by injection, the desired effect of promoting periodontal tissue regeneration is exerted.
実施例 次に実施例を挙げて本発明をさらに詳しく説明する。Example Next, the present invention will be explained in more detail with reference to Examples.
実施例１
成分 量
Ｎ−ｙセｆルーＤ−７ン／ ０．００２ｇサミン（
シグマ社製）
生理食塩水 全量１００ｇに調整これらの
成分を混合溶解し、無菌濾過して液剤を得る。Example 1 Ingredients Amount
(manufactured by Sigma) Physiological saline Adjust the total amount to 100 g. Mix and dissolve these components and filter aseptically to obtain a liquid preparation.
実施例２
成分 量
Ｎ−アセチル−Ｄ−ガラクト ０．０１ｇサミノダイ
マー（フナコシ薬品）
ステアリン酸 ２ｇセタノール
０．５ｇウラノリ２ｇ
イソプロピルミリステート２ｇ
スクワラン ３ｇ流動パラフ
ィン ８ｇポリオキシエチレンセ
チル １．７ｇエーテル
トリエタノールアミン Ｉｇグリセリン
４ｇ防腐剤
適量精製水 全ｊｌｌｏ
ｏｇに調整これらの成分を用い、常法に従って乳液を得
る。Example 2 Ingredients Quantity N-acetyl-D-galacto 0.01 g Samino dimer (Funakoshi Pharmaceutical) Stearic acid 2 g Cetano 0.5 g Uranori 2 g Isopropyl myristate 2 g Squalane 3 g Liquid paraffin 8 g Polyoxyethylene cetyl 1.7 g Ether triethanolamine Ig Glycerin 4g preservative
Appropriate amount of purified water whole jllo
Using these ingredients, a milky lotion is obtained according to a conventional method.
実施例３
成分 量
Ｎ−アセチルーＤ−グルコ ０．０１ｇサミノト
ライマー
ラウリル硫酸ナトリウム ０．２ｇカルボキ
シメチルセルロース ２ｇグリセリン
４０ｇ精製水 全１！
１００ｇに調整これらの成分を混合し、ゲル剤を得る。Example 3 Ingredients Amount N-acetyl-D-gluco 0.01g Saminotrimer Sodium Lauryl Sulfate 0.2g Carboxymethylcellulose 2g Glycerin
40g purified water total 1!
These ingredients were adjusted to 100 g and mixed to obtain a gel.
Ｎ−アセチル−Ｄ−グルコサミン、Ｎ−アセチル−Ｄ−
ガラクトサミン、Ｎ−アセチル−Ｄ−マンノサミンおよ
びこれらのアミノ糖がα−またはβ−１，４結合による
オリゴ糖の歯周組織再生促進作用を試験した。以下にそ
の結果を示す。N-acetyl-D-glucosamine, N-acetyl-D-
Galactosamine, N-acetyl-D-mannosamine, and these amino sugars were tested for their activity in promoting periodontal tissue regeneration through α- or β-1,4 linkages. The results are shown below.
（１）歯根膜線維芽細胞の運動性に対する作用ヒト抜去
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−アセチル化アミノ
糖およびオリゴ糖を有する歯根膜線維芽細胞および歯肉
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４８穴マイクロチヤンバー法により測定した
。(1) Effect on the motility of periodontal ligament fibroblasts Periodontal ligament fibroblasts were primary cultured from the periodontal ligament remaining in human extracted teeth, and epithelial cells from the gingival tissue were cultured, and various N-acetylated amino sugars and oligosaccharides were cultured. Chemotactic activity toward periodontal ligament fibroblasts and gingival epithelial cells was measured by a 48-hole microchamber method using a filter with a pore size of 8 microns.
５．０ＸＩＯ”個／ｌｎＱの細胞懸濁液をチャンバーの
王室に、下室には各種のＮ−アセチル化アミノ糖および
オリゴ糖を１０〜１００μｇ／−の割合で加え、３７℃
で４時間インキュベートした。ついでフィルターを固定
し、デイツークイック（Ｄ ｉｆＴ −Ｑ ｕｉｃｋ）
染色後、フィルターの底部まで遊走した細胞数を顕微鏡
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１００％とした場合のＮ−
アセチル化アミノ糖およびオリゴ糖添加時の相対的割合
を第１表に示す。A cell suspension of 5.0XIO" cells/lnQ was added to the royal chamber of the chamber, and various N-acetylated amino sugars and oligosaccharides were added at a rate of 10 to 100 μg/- to the lower chamber, and the mixture was incubated at 37°C.
and incubated for 4 hours. Then, fix the filter and use DifT-Quick.
After staining, the number of cells that migrated to the bottom of the filter was counted under a microscope. As a control, a similar test was conducted without adding the specimen. N- when the coefficient value of the control is taken as 100%
Table 1 shows the relative proportions of acetylated amino sugars and oligosaccharides.
第１表
第１表に示すごとく、
Ｎ−アセチル−Ｄ−グル
コサミンとそのダイマー、
トライマー、
Ｎ−アセ
チルーＤ−ガラクトサミンとそのダイマー、トライマー
、さらにＮ−アセチル−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
、歯肉上皮細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織再生の中心となる
歯根膜線維芽細胞のみをより選択的に病変部位に遁走せ
しめる作用を有する。Table 1 As shown in Table 1, N-acetyl-D-glucosamine and its dimer and trimer, N-acetyl-D-galactosamine and its dimer and trimer, and N-acetyl-D-mannosamine are all found in the periodontal ligament. It had specific chemotactic activity against fibroblasts and had little effect on gingival epithelial cells. As a result, these drugs clearly have the effect of more selectively forcing periodontal ligament fibroblasts, which play a central role in periodontal tissue regeneration, to escape to the lesion site.
Ｃ２＞ｍ根膜線維芽細胞の増殖性に対する作用各種Ｎ−
アセチル化アミノ糖およびオリゴ糖の歯根膜線維芽細胞
の増殖性に対する作用を測定した。C2>mEffects of various N- on proliferation of root membrane fibroblasts
The effects of acetylated amino sugars and oligosaccharides on the proliferation of periodontal ligament fibroblasts were measured.
直径３５ｍｍの組織培養用シャーレに歯根膜線維芽細胞
３．０Ｘ１０’個を播種し、３７°Ｃで１日インキュベ
ート後、各種Ｎ−アセチル化アミノ糖およびオリゴ糖を
ｌＯＯμｇ／ｍ１２の割合で加え、さらに３７°Ｃで２
日インキュベートした。ついで細胞を０．１５％トリプ
シン溶液でシャーレより剥離し、細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。3.0 x 10' periodontal ligament fibroblasts were seeded in a tissue culture dish with a diameter of 35 mm, and after incubating at 37 °C for 1 day, various N-acetylated amino sugars and oligosaccharides were added at a rate of 10 μg/m12. 2 more at 37°C
Incubated for 1 day. The cells were then detached from the petri dish using a 0.15% trypsin solution, and the number of cells was counted using a hemocytometer. As a control, a similar test was conducted without adding the specimen.
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。Table 2 shows the number of cells proliferated in the petri dish for each specimen.
第２表
第２表に示すごとく、Ｎ−アセチル−Ｄ−グルコサミン
とそのダイマー、トライマー、Ｎ−アセチル−Ｄ−ガラ
クトサミンとそのダイマー、トライマー、さらにＮ−ア
セチル−Ｄ−マンノサミンは、いずれもが歯根膜線維非
細胞の増殖性を高めた。Table 2 As shown in Table 2, N-acetyl-D-glucosamine and its dimer and trimer, N-acetyl-D-galactosamine and its dimer and trimer, and N-acetyl-D-mannosamine are all found in tooth roots. Increased proliferation of membrane fiber non-cells.
（３〉イヌ歯肉剥離掻爬手術後の歯周組織再生過程に対
する作用
イヌ歯肉剥離掻爬手術後の歯周組織再生過程に対する各
種Ｎ−アセチル化アミノ糖およびオリゴ糖の作用を病理
組織学的定量評価法により検討した。ブラッシング等に
より健常な歯周組織を確立した上下顎小臼歯部に、常法
に従って歯肉剥離掻爬手術を施した。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、左側
上下顎の露出した根面上に１部位当り５０Ｒ９を投与し
、対照として右側上下顎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、縫合とパックによ
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、顕微鏡下で
接眼マイクロメーターを用いて各部位間の距離を測定し
、以下の基準で定量化した。(3) Effect on periodontal tissue regeneration process after canine gingival avulsion curettage surgery Histopathological quantitative evaluation of the effects of various N-acetylated amino sugars and oligosaccharides on the periodontal tissue regeneration process after dog gingival abrasion curettage surgery Gingival abrasion curettage was performed according to the conventional method on the upper and lower bicuspids where healthy periodontal tissue had been established by brushing etc. At this time, this was done to serve as a reference point for later histopathological quantification. A reference point called a notch was added to the root surface before and after the removal of the alveolar bone.The specimen was a gel similar to that shown in Example 3, and one site was placed on the exposed root surface of the left upper and lower jaws. 50R9 was administered, and as a control, a gel containing no drug was administered to the right upper and lower jaw.After the surgery, the gingival flap was repositioned and protected with sutures and a pack for 1 week.Evaluation was performed 4 weeks after the surgery. After collecting the test site and preparing a tissue specimen using a conventional method, the distance between each site was measured using an eyepiece micrometer under a microscope, and quantified using the following criteria.
■＝上皮のダウングロース率（％） ２：線維性付着率（％） 線維が垂直および斜走する部分の長さ 結果を表３に示す。■ = Epithelial downgrowth rate (%) 2: Fibrous attachment rate (%) Length of vertical and oblique fibers The results are shown in Table 3.
第３表
第３表に示すごとく、
Ｎ−アセチル
ガラ
クトサミンとそのトライマー、さらにＮ−アセチル−Ｄ
−ゲ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、線維性付着率に対しては明
らかに促進作用を示した。Table 3 As shown in Table 3, N-acetylgalactosamine and its trimer, as well as N-acetyl-D
-Gelcosaminotrimer slightly suppressed epithelial downgrowth and clearly promoted the rate of fibrotic attachment.
以上の結果から明らかなごとく、Ｎ−アセチル化アミノ
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 effects.
発明の効果
本発明によれば、歯周炎の治療に有用な、安全性、安定
性および有効性に優れた歯周組織再生促進剤が得られる
。Effects of the Invention According to the present invention, a periodontal tissue regeneration promoter that is useful in the treatment of periodontitis and has excellent safety, stability, and effectiveness can be obtained.
Claims (1)
−Ｄ−ガラクトサミン、Ｎ−アセチル−Ｄ−マンノサミ
ンおよびこれらがα−またはβ−１，４−結合したオリ
ゴ糖からなる群から選ばれるＮ−アセチル化アミノ糖を
活性成分として含有することを特徴とする歯周組織再生
促進剤。(1) N- selected from the group consisting of N-acetyl-D-glucosamine, N-acetin-D-galactosamine, N-acetyl-D-mannosamine, and oligosaccharides in which these are α- or β-1,4-linked. A periodontal tissue regeneration promoter characterized by containing an acetylated amino sugar as an active ingredient.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1220031A JPH0383927A (en) | 1989-08-25 | 1989-08-25 | Periodontal tissue regeneration promoter |
| PCT/JP1990/001066 WO1991002530A1 (en) | 1989-08-25 | 1990-08-22 | Accelerator for periodontal tissue regeneration |
| CN90107588A CN1052045A (en) | 1989-08-25 | 1990-08-25 | The preparation method of paradenlal tissue regeneration promoter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1220031A JPH0383927A (en) | 1989-08-25 | 1989-08-25 | Periodontal tissue regeneration promoter |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0383927A true JPH0383927A (en) | 1991-04-09 |
Family
ID=16744846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1220031A Pending JPH0383927A (en) | 1989-08-25 | 1989-08-25 | Periodontal tissue regeneration promoter |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPH0383927A (en) |
| CN (1) | CN1052045A (en) |
| WO (1) | WO1991002530A1 (en) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5362480A (en) * | 1991-12-31 | 1994-11-08 | Lever Brothers Company, Division Of Conopco, Inc. | Oral hygiene compositions containing amino sugars as antiplaque agents |
| US5286480A (en) * | 1992-06-29 | 1994-02-15 | The Procter & Gamble Company | Use of N-acetylated amino acid complexes in oral care compositions |
| CN1173706C (en) | 2001-02-28 | 2004-11-03 | 中国人民解放军第三军医大学 | Application of N-acetyl-D-aminoglucose in preparing medicines to treat cervical erosion |
| CN1199645C (en) | 2002-08-13 | 2005-05-04 | 中国人民解放军第三军医大学 | Application of N-acetyl-D-aminoglucose in the preparation of medicine for treating urogenital system infection |
| CN1210038C (en) | 2003-03-27 | 2005-07-13 | 中国人民解放军第三军医大学 | Application of N-acetylglucosamine in the preparation of medicine for treating viscera injure due to toxication from poison and medicine |
| PT1951184E (en) | 2005-11-09 | 2012-04-10 | Klox Technologies Inc | Teeth whitening compositions and methods |
| JP5478631B2 (en) | 2008-11-07 | 2014-04-23 | クロクス テクノロジーズ インコーポレイテッド | Combination of oxidant and photoactivator for wound healing |
| BR112012001016A2 (en) | 2009-07-17 | 2020-10-27 | Klox Technologies Inc. | antibacterial oral composition |
| US20130281913A1 (en) | 2012-04-20 | 2013-10-24 | Klox Technologies Inc. | Biophotonic compositions and methods for providing biophotonic treatment |
| US11116841B2 (en) | 2012-04-20 | 2021-09-14 | Klox Technologies Inc. | Biophotonic compositions, kits and methods |
| US20140105832A1 (en) | 2012-09-14 | 2014-04-17 | Valeant Pharmaceuticals International, Inc. | Compositions and methods for teeth whitening |
| US20140276354A1 (en) | 2013-03-14 | 2014-09-18 | Klox Technologies Inc. | Biophotonic materials and uses thereof |
| MX366292B (en) | 2013-07-03 | 2019-07-04 | Klox Tech Inc | Biophotonic compositions comprising a chromophore and a gelling agent for treating wounds. |
| US10328010B2 (en) * | 2013-12-27 | 2019-06-25 | Colgate-Palmolive Company | Prebiotic oral care methods using a saccharide |
| EP3125963B1 (en) | 2014-04-01 | 2019-11-20 | Klox Technologies Inc. | Tissue filler compositions and methods of use |
| KR20170077153A (en) | 2014-10-31 | 2017-07-05 | 클록스 테크놀로지스 인크. | Photoactivatable fibers and fabric media |
| US11696879B2 (en) * | 2016-05-26 | 2023-07-11 | 3M Innovative Properties Company | Therapeutic dental pastes and related methods and kits |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5811927B2 (en) * | 1978-11-16 | 1983-03-05 | サンスタ−株式会社 | Oral composition |
| JPS60142923A (en) * | 1983-12-28 | 1985-07-29 | Lion Corp | Drug for periodontosis |
| JPS62294607A (en) * | 1986-06-13 | 1987-12-22 | Kanebo Ltd | Oral cavity composition |
-
1989
- 1989-08-25 JP JP1220031A patent/JPH0383927A/en active Pending
-
1990
- 1990-08-22 WO PCT/JP1990/001066 patent/WO1991002530A1/en unknown
- 1990-08-25 CN CN90107588A patent/CN1052045A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO1991002530A1 (en) | 1991-03-07 |
| CN1052045A (en) | 1991-06-12 |
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