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TW201113042A - Tooth polishing compositions and methods of tooth polishing without mechanical abrasion - Google Patents

Tooth polishing compositions and methods of tooth polishing without mechanical abrasion Download PDF

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Publication number
TW201113042A
TW201113042A TW98123960A TW98123960A TW201113042A TW 201113042 A TW201113042 A TW 201113042A TW 98123960 A TW98123960 A TW 98123960A TW 98123960 A TW98123960 A TW 98123960A TW 201113042 A TW201113042 A TW 201113042A
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Taiwan
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composition
tooth
gel
polishing
chlorine dioxide
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TW98123960A
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Chinese (zh)
Inventor
Barry Keven Speronello
Frank S Castellana
Linda Hratko
Steven R Jefferies
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Basf Catalysts Llc
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Publication of TW201113042A publication Critical patent/TW201113042A/en

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Abstract

A method of polishing a tooth surface without mechanical abrasion is provided. Kits and compositions are also provided.

Description

201113042 六、發明說明: 【先前技術】 作為專業牙科工作者之常規牙科 , 〇竹頂防工作之一部分,牙 齒係由包含一或多種軟質研磨劑 貞 J之組合物拋光。拋光可用 來增加牙齒表面之平滑度,從而使 < T回表面裒佳化且使表 面缺陷降至最低程度,用來移降# _ 反用+秒陈表面巧潰(外來污潰),增 加針對表面污染之抵抗力’ 1用來移除牙菌斑及表臈 (pelhcle)’從而防止或降低齒齦疾病之風險'然而,牙齒 研磨可隨時間過去最終磨損琺螂 外’人們在其顯現外來污潰及牙 質、齒質及齒堊質。另 菌斑之傾向方面為不同 的。此外,在存在牙齒表面腐餘(諸如由酸引起之彼腐⑷ 的情況下,對研磨之敏感性增加(Hunter等人,2〇〇2, 7此201113042 VI. Description of the Invention: [Prior Art] As a part of the routine dentistry of professional dentists, the dental system is polished by a composition comprising one or more soft abrasives. Polishing can be used to increase the smoothness of the tooth surface, so that the T back surface is improved and the surface defects are minimized, used to shift # _ anti-use + second surface crack (external fouling), increase Resistance against surface contamination '1 is used to remove plaque and pelhcle' to prevent or reduce the risk of gum disease. 'However, tooth grinding can eventually wear out over time. 'People appear outside of it. Stain and dentin, tooth and gum. The tendency of plaque is different. In addition, the sensitivity to grinding is increased in the presence of tooth surface rot (such as the rot caused by acid (4) (Hunter et al., 2 〇〇 2, 7

Dm·义52: 399-405)。酸選擇性移除牙齒之某些組份,從 而藉由增加表面積及表面粗糙度而腐蝕牙齒表面。已知過 氧化物具有類似效應。因此’需要謹慎選擇拋光材料及技 術以使每一患者之污潰移除與牙齒表面完整性達到平衡。 當前存在三種主要類型之用於拋光牙齒之研磨劑:磷酸 鹽,包括正磷酸鹽、聚偏磷酸鹽及焦磷酸鹽;碳酸鹽;及 二氧化矽。氡化鋁亦用作研磨劑。研磨劑可見於牙膏配方 以及預防糊劑(prophylaxis paste)兩者中。預防糊劑為甴牙 科醫師及/或牙科衛生士專業地用於拋光牙齒之產品。其 他研磨劑包括樹脂研磨材料,諸如尿素及曱醛之微粒墙合 產物’及美國專利第3,070,5 10號揭示之彼等者。 專業抛光包括由低速裝置驅動之機械拋光端部 141702.doc 201113042 (mechanical polishing tip)(例如橡膠皮碗或刷子)及/或空氣 拋光。機械拋光端部可單獨使用或與預防糊劑一起使用。 空氣拋光使用空氣、碳酸氫鈉及喷水以移除污潰且拋光牙 齒。除不當牙齒研磨之風險之外,當前專業拋光技術之某 些其他問題包括預防糊劑之濺潑、由拋光端部之摩擦熱所 引起之不適、經腐#之牙齒表面之敏感性,及軟組織(包 括齒齦、舌及嘴唇)對於空氣拋光之敏感性。另外,對於 齒垦質或齒貝曝疼之患者而言,空氣拋光為不可取的。 二氧化氯(Cl〇2)作為消毒劑以及強氧化劑為吾人所熟 知。二氧化氯之殺細菌、殺藻、殺真菌、漂白及除臭性質 亦為熟知的。 氧化氯(Cl〇2)為呈+IV氧化態之氯之中性化合物 具 藉由氧化來消毒。然而,其不具有氯化作用。其為相對較 小、具有揮發性且高能之分子,且甚至在呈稀水溶液形式 時亦為游離基。歸因於在二氧化氣經還原為亞氯酸根 (Cl〇2·)的情況下其單電子轉移機制,二氧化氯充當高度選 擇性氧化劑。在PH Μ下’亞氣酸根離子/亞氣酸平衡之 PKa值極低。此顯著地不⑽在接近中性的情況下所見到 之次氣酸/次氣酸根驗離子對平衡,且指示亞氯酸根離子 作為主要物質存在於飲用水中。 二氧化氯之最重要的一種物理性質為其於水中、尤1於 冷卻水中之高溶解度。與氯氣在水中水解對比,水中之二 :化氯不會在任何明顯程度上水解’而以溶解氣體形式保 持於溶解狀態中。 141702.doc 201113042 ^ 製備二氧化氯之傳統方法包括使亞氣酸鈉與氣i氯 (Cl2(g))、次氯酸(HOC1)或氬氯酸(HC1)反應。反應為: 2NaC102+Cl2(g)=2C102(g)+2NaCl [la] 2NaC102+H0Cl=2C102(g)+NaCl+Na0H [lb] • 5NaC102+4HCl=4C102(g)+5NaCl+2H20 [lc] ' 反應[la]及[lb]在酸性介質中以更大之速率進行,因比實 質上所有常規二氧化氯生成化學過程產生pH值低於3.5之 酸性產物溶液。又,因為形成二氧化氯之動力學在亞氣酸 根陰離子濃度方面為高階的,所以二氧化氯生成一般在較 高濃度(>1〇〇〇 ppm)下完成,必須將其稀釋至用於應用之 使用濃度。 二氧化氯亦可自氯酸根陰離子藉由酸化或酸化及還原之 組合來製備。該等反應之實例包括: 2NaC103+4HC1^2Cl〇2+Cl2+2H20+2NaCl [2a] 2HCl〇3+H2C2〇4^2Cl〇2+2C〇2+2H2〇 [2b] 2NaC103+H2S04 + S02 今 2C102 + 2NaHS04 [2c] 在周圍條件下,所有反應需要強酸性條件;最常見在7-9 to N之範圍内。將試劑加熱至較高溫度及自產物溶液連續移 除二氧化氯可將所需酸性降低至小於1 N。 原位製備二氧化氣之方法使用稱為「安定化二氧化氤」 之溶液。安定化二氧化氯溶液含有極少或不含有二軋化 氯,而是實質上由中性或弱鹼性pH值下之亞氯酸鈉組成。 141702.doc 201113042 將酸添加至亞氣酸鈉溶液中可活化亞氣酸鈉,且原位在溶 液中生成二氧化氣。所得溶液為酸性的。通常,亞氯酸鈉 轉化為一氧化氣之程度為較低的且大量亞氯酸鈉保留於溶 液中。 美國專利第6,582,682號揭示包含「安定化二氧化氣」之 口腔護理組合物’其在曝露於口腔中之適度酸性pH值後產 生二氧化氣。 美國專利第6,479,037號揭示製備用於牙齒美白之二氧化 氯組合物,其令組合物藉由將二氧化氯前驅體(CDp)部分 與酸化劑(ACD)部分組合來製備。CDp部分為pH值大於7 之金屬亞氯酸鹽溶液。ACD為酸性的,例如具有3 〇至4.5 之PH值。將CDP塗覆於牙齒表面。隨後將acd塗覆於 上以活化金屬亞氯酸鹽且產生二氧化氣。接觸界面處之0 值可小於6且在約3.0至4.5之另一範圍卜目此牙齒表面 上之所得二氧化氣組合物為酸性的。另外,此方法可能會 使:腔黏膜受到與強烈高度酸性試劑(ACD)接觸的影響。 吳國專利第6,432,387號揭*在口巾生成負離子,從而在 研磨劑及侵襲性職之量得以降低的情況下有效淨 之牙齒抛光劑。 之牙齒拋光組合物 然而在此項技術中仍需要降低副作用 及方法。 【發明内容】 以下發明内容並 之關鍵性或決定 以下實施例滿足且著手解決此等需要。 非詳盡概述。其既未用來確定各種實施例 141702.doc 201113042 性要素’亦未描述其範疇。 本文中提供—種拋光牙齒表面之方法。該方法包含使牙 歯表面與有效量之包含非研磨性拋光劑之拋光組合物接 觸,其中非研磨性拋光劑包含二氧化氣。在一實施例卜 組合物為實質上非細胞毒性的。在某些實施例中,拋光組 合物包^少於約0.2毫克氧'氣陰離子/公克組合物。 在一貫施例中’拋光組合物包含約5至約刪啊二氧 化氯。在另-實施例中,拋光組合物包含約3〇至約4〇 p㈣ 一氧化風。在某些實施例中,抛光組合物具有約4.5至約 u之阳值。在其他實施例中,抛光組合物具有約5至射之 PH值,或大於約6且小於約8之{^值。 ::些:施例中’拋光組合物可為包含稠化劑組份之稠 祖、‘且&物。在稍化流體組合物之某些實施例中,稠化 劑組份係選自由天然水勝體、半合成水膠體、合成水膠體 =體έ土二成之群。在—實施例中’稠化劑組份為半 膠體。例示性半合成水穋體為叛甲基纖維 纖維素鈉。 3硬r暴 在該方法之某些實施例中,# 吏牙組合物接觸會降低 度。其表面粗糙度比牙齒表面_ α物接觸之别之表面粗糙度降低至少約。 在某些實施例中,使牙齒與組合物接觸不 牙齒硬組織;不會實質性降㈣«顯微硬度;不合^ 性降低齒質顯微硬度,·及/或不會導致牙齒敏感性。"、貝 在一實施例中’組合物為實質上非刺激性。在某此實施 141702.doc 201113042 例中’組合物接觸口歷軟組織。在某些實施例中,不需要 保護齒齦:在某些實施例中,組合物視情況為漱口水。 在另#樣中,提供一種拋光牙齒表面之方法,其包含 使牙齒表面與有效量之包含非研磨性拋光劑之組合物接 觸,其中非研磨性拋光劑包含二氧化氯且其中接觸牙齒表 面之步驟引起組合物與口腔軟組織之實質性接觸。在一實 施例中’組合物為實f上非細胞毒性。在某些實施例中, 抛光心物包含少於狀2毫克氧·氯陰離子/公克組合物。 在另-實施例中’組合物為實質上非刺激性。 在實細例中,拋光組合物包含約5至約!咖沖⑺二氧 化氣。在另一實施例中,拋光組合物包含約30至約40 ppm 二氧化氯。在某些實施例中,拋光組合物具有約七5至約 U之阳值。在其他實施例中,拋光組合物具有約5至約9之 pH值,或大於約6且小於約8之值。 在某些實施例中,拋光組合物可為包含稠化劑組份之稠 化流體組合物。在㈣流體組合物之某些實施例中,稠化 劑組份係選自由天然水膠體、半合成水膠體、合成水膠體 ^黏土組成之群。在-實施例中,稠化劑組份為半合成水 /體例;丨生半合成水膠體為缓甲基織維素,諸如缓甲基 纖維素鋼。 在該方法之某些實施例中,使牙齒與組合物接觸會降低 -表面之表面粗縫度。與使牙齒表面與拋光組合物接觸 之前之表:粗糙度相比,表面粗糙度可降低至少約5%。 某一貫鈿例中,使牙齒與組合物接觸不會實質性損傷 141702.doc 201113042 牙齒硬組織;不會實質性降低琺螂質顯微硬度;不會實質 性降低齒質顯微硬度丨及/或不會導致牙齒敏感性。3貝 在一實施例中,組合物為實質上非刺激性的。在某些實 施例中,組合物接觸口腔軟組織。在某些實施例中,不需 要保護齒齦。在某些實施例中,組合物視情況為漱口水。 亦提供一種製備牙齒拋光組合物之套組。套組包含第一 施配器,其包含一氧化氯之微粒前驅體;第二施配器,其 包含水性介質中之稠化劑組份;及用於製備包含有效用於 牙齒拋光之量之二氧化氯之實質上非細胞毒性組合物的教 材。在一實施例中,該第一施配器及該第二施配器中之至 少一者為注射器。稠化劑組份可選自由天然水膠體、半合 成水膠體、合成水膠體及黏土組成之群。在一實施例令, 稠化劏組份為半合成水膠體。例示性半合成水勝體為羧甲 基纖維素’諸如羧甲基纖維素鈉。 【實施方式】 出於說叼組合物、套組及方法之目的,在圖式中描述特 夂只%例。然而,組合物、套組及其使用方法不侷限於圖 式中所描述之實施例之精確配置及手段。 本文中描述使用不包含研磨劑之組合物拋光牙齒之方 法。在另一實施例中,組合物為非細胞毒性的且包含二氧 化氣。 定義 除非另作定義,否則本文中所用之所有技術及科學術語 一般具有與一般熟習此項技術者通常所瞭解之含義相同的 141702.doc -9- 201113042 含義。本文中使用之命名法及細胞病變分析、微生物分 析、有機及無機化學及牙科臨床研究中之實驗室程序一般 為在此項技術中熟知且常用之彼等命名法及實驗室程序。 如本文中所用,以下術語中之每一者在此部分中具有與 其相關之含義。 本文中使用冠詞「一」以指代冠詞之文法受詞之一者或 -者以上(亦即至少-者)。舉例而言,「一要素」意謂一個 要素或一個以上要素。 術語「約」由一般熟習此項技術者所理解且取決於其使 用之上下文而在某種程度上變化。一般而言,「約」包涵 為參考值+/_ ιο%之值範圍。例如,「約25%」包涵 27.5%之值。 應瞭解本文中M明之任何範圍之間之全整數或部分整數 包括於其中。 其二水合物。 本文中使用「拋光」以指代處理牙齒表面以達成以下令 之至;一者的方法:降低表面粗糙度(相當於增加表面平 滑度);移除外來污潰;及移除牙菌斑。 槿Π文I所用之「表面粗糙度」係指牙齒表面之微觀結 籌,,、h表面粗糖度可依據在此項技術中已知之若干參數 來量測’該等參數包括 数匕括(但不限於)平均表面粗糙度Ra,· q(亦稱為RMS ;均方根粗縫度) ^^ 0 ’ Kt(忒樣表面上之最大粗 ),叫平均最大峰谷高度);及尺叫最大表面粗_ 141702.doc 201113042 度)。表面粗糖度可依據平均表面粗趟度Ra來量測。⑽ 在取樣長度内所量測之針對中線之粗糙分量不規則之算術 平均回度。k小Ra值指示較平滑表面。表面粗链度可藉由 在此項技術中已知用於晉钏β。4 7 ^ 用於里測Ra之任何方法(諸如表面輪廓 量測術、纟面掃描方法及原子力顯微術)來量測。可在至 少-處理時段之後且在任何隨後實質性曝露於其他作用物 (例如再礦物化溶液(包括唾液))之前量測表面粗链度。 如本文中所用之「研磨」係指由外來材料或作用物磨損 諸如綠瑯質或齒質之物質。如本文中所用之「研磨劑」為 可用於機械研磨牙齒物質之化合物或材料。 如本文中所用,「肩钮」係指由於酸(外源性及/或内源 性)及/或螯合劑作用於牙齒表面所引起之牙齒表面之化學 侵钱0 如本文中所用之「非研磨性拋光劑」係指在無需機械研 磨的情況下可量測地降低牙齒表面祕度之任何化合物, 或化合物之組合。例示性非研磨性拋光劑亦可為非腐钱性 的。 如本文中所用之化學拋光」係指使用非研磨性抛光劑 進行拋光。 如本文中所用’拋光劑之「有效量」用來意謂將導致藉 由-或多次處理而拋光牙齒表面之拋光劑的任何量。有效 量為導致降低牙齒表面粗糙度之量。 如本文中所用,細胞毒性」係指對於哺乳動物細月包結 構或功能造成致死性損傷之性質。#當活性醫藥成份 141702.doc -11 - 201113042 (API)以有效量存在時’組合物滿足USp<87>「活體外生物 反應性」之瓊脂擴散測試(2〇07年批准之現行方案)之美國 藥典(the United States Pharmacopeia; USP)生物反應性限 度,則認為組合物為「實質上非細胞毒性的」或「非實質 性細胞毒性的」。 如本文中所用,「刺激」係指藉由即刻、長期或重複接 觸而造成局部發炎反應(諸如變紅、膨脹、發癢、灼傷或 起/包)之I"生質。若使用έ平定口腔黏膜刺激之任何標準方法 判定組合物為輕微或無刺激性的,則認為組合物為「實質 上非刺激性的」或「非實質性刺激性的」。該等方法之非 限制性實例包括:HET_CAM(雞蛋測試'織毛尿囊膜);蛞 輸黏膜刺激㈣;及使用_卫程口腔黏膜之活體外測 試。 如本文中所用’「牙齒硬組織」係指瑞瑯質及齒質中之 至少一者。 如本文中所用,「牙齒硬組織損傷」係指以下中之至少 -者:琺螂質之顯微硬度降低、齒質之顯微硬度降低。 如本=中所用,若滿足以下中之—或多者,則組合物 不“貝哇知铴牙齒硬組織」:】)琺瑯質顯微硬度減少 量小於约15% ’及/或在5%信賴水準下,降低並非統計上 顯著的;及2)齒質顯微硬度減少量小於約15%,及/或在冰 信賴水準下,降低並非統計上顯著的。 士本文中所用’「氧-氯陰離子」係指亞氯酸根(⑽2·)及/ 或氯酸根(cio3·)離子。 141702.doc 201113042 如本文中所肖,「實質性純二氧化氯溶液」係指具有非 細胞毒性濃度之氧-氯陰離子之二氧化氯之溶液。如本文 中所用實貝性純二氧化氣溶液」亦係指含有一定濃度 之氧-氯陰離子之二氧化氯之濃溶液,其在稀釋至有效量 之二氧化氯後,相關於氧-氯陰離子之漠度而言並非細胞 毒性的。 短語「稍化流體組合物」包涵可在所施加之剪應力下流 動且當流動時具有大於相同濃度之相應二氧化氯水溶液之 黏度之表觀黏度的組合物。此包涵全部範圍之揭化流體組 合物,該等稠化流體組合物包括:展現牛頓流動之流體 (其中剪切速率與剪應力之比率為^的且黏度盘剪岸力 無關)、搖變減黏流體(其需要在流動之前克服最小屈服岸 力,且其亦展現隨著剪切持續 了戶、叩刀切稀化)、假塑性及塑 性流體(其需要在流動之前克服最小屈服應力)、加壓㈣ 流體組合物(其隨著剪料率增Μ表㈣度上旧及可在 所施加之屈服應力下流動之其他材料。 如本文中所用之短語「稠化齊“且份」係指具有使添加盆 之洛液或混合物稠化之性質的組份。「稍化劑組份」用以 製得如上所述之「稠化流體組合物」。 —短表觀黏度」疋義為在引起流動之任何剪切條件設 疋下之剪應力與剪切速率之比率。對料頓流體而言 觀黏度t剪應力無關’且對於非牛頓流體組合物而言,表 觀黏度隨剪切速率而變化。 本文中使用術語「微粒」以指代所有固體材料。作為非 141702.doc •13· 201113042 限制it實例,微粒可彼此散置以在某種方式下彼此接觸。 此等固體材料包括任何大小之顆粒,及不同大小之顆粒的 組合。 描述 本文中描述之组合物、套組及使用方法部分地來源於以 a見使牙齒表面與一氧化氯組合物接觸可在對於牙齒 軟及硬組織之損傷減少至最低程度的情況下降低牙齒表面 粗链度。特定言之,在5%信賴水準下,:氧化氯組合物 在統计上顯著水準上降低琺瑯質之平均表面粗糙度。在某 些貫施例中,二氧化氯組合物可為非細胞毒性的及/或非 刺激性的。在某些態樣中,琺瑯質之表面粗糙度與處理之 前之表面粗糙度相比降低至少約5%,或至少約8%,或甚 至至少約10%。在一實施例巾’琺瑯質平均表面粗糙度與 處理之前之平均表面粗糙度相比降低至少約12%。在其他 實施例中,齒質之平均表面粗糙度不以統計上顯著量增 加另外Μ吳上非細胞毒性及非刺激性之含有二氧化氯 之組合物有利地不在顯著程度上不利地影響接鄉質或齒質 顯微硬度,且因此不會實質性損傷牙齒硬組織。 、 因此,在一態樣中,提供一種化學拋光牙齒之方法。特 定言之,該方法包含使牙齒表面與有效量之實質上非細胞 毒性組合物接觸,其中該組合物包含在無需機械研磨的情 況下拋光所接觸之牙窗表面之拋光劑。有利地,不需要拋 光端部或喷水來實施該方法。因此,當使用本文中描述 組合物、套組及方法時,避免與此等用具相關之不當副 141702.doc -14- 201113042 用。另外,涵盍一種尤其適用於具有經腐蝕之琺瑯質及/ 或tel堊貝且具有曝露之齒質的患者的方法。與琺瑯質相 比,齒質對於研磨更敏感且咸信其構成牙齒敏感性之基 礎。因此,預期非研磨性拋光方法可保持齒質結構完整性 且從而使顯現牙齒敏感性之風險降至最低程度。 I.組合物 用於實施該方法之組合物為包含非研磨性拋光劑之水性 流體,其中該拋光劑為二氧化氯。在其他實施例中,組合 物可為實質上非細胞毒性的,實質上非刺激性的,及其組 合。在某些實施例中,組合物包含使組合物成為稠化水性 流體之稠化劑組份。在其他實施例中,組合物可為可保持 於口中、與牙齒以及軟組織接觸之漱口水。 適用於貫施該方法之組合物包含至少約5 ppm,或至少 約20 ppm ’或甚至至少約3〇 ppm之二氧化氯。通常,二氧 化氯之量可為至多約1〇〇〇 ppm,或至多約7〇〇 ,或至 夕約500 ppm,或至多約2〇〇 ppm。在某些實施例中,二氧 化氣濃度在約5至約700 ppm ’或約20至約5〇〇 ppm,或約 30至約200 ppm二氧化氣之範圍内。在一實施例中,組合 物包含約30至約40 ppm二氧化氯。在一實施例中,組合物 包含約30 PPm。在另一實施例中’組合物包含約40 ppm。 軟組織刺激可由高度反應性氧物質(諸如可見於以過氧 化物為主之組合物中之彼等物質)產生。軟組織刺激亦可 由酸性及鹼性兩者之pH極限值產生。為使含有二氧化氯之 組合物對軟組織之刺激降至最低程度’實質上非細胞毒性 141702.doc -15· 201113042 ^物具有至少約3 5之婦。為使可能的硬表面腐飯降 取低程度’組合物具有至少約4.5之阳值。組合物可具 有至八力5 ’ J'更佳大於約6之PH值。在某些實施例中, PH值在約4.5至約11,更佳約5至約9,且更佳大於約6且小 於約8之範圍内。在-實施例中,PH值為約6.5至約7 5。 咸^刺激並非由氧·氯陰離子之濃度產生。因為組合物可 為實質上非刺激性的,所以不需要在處理之前保護凿銀或 其他口腔軟組織以免刺激。 對於如本文♦所示之包含二氧化氣之組合物而言,細胞 毒性主要由所存在之氧_氣陰離子產生。因此,在不存在 造成細胞毒性之其他組份的情況下,包含〇毫克(mg)氧-氣 陰離子/公克組合物至不超過約〇 25 11^氧_氣陰離子/公克 組合物’較佳0至約〇·24、〇.23、〇·22、〇 21或〇 2〇叫氧· 氣陰離子/公克組合物,更佳0至約0.19、0.18、〇.17、 (M6 〇·15、〇·ΐ4、0.13 ' 0.12、〇·11 或 〇.1〇 „^氧_ 氯陰離 子/公克組合物,且更佳0至約〇 〇9、〇 〇8、〇 〇7、〇 〇6、 0.05或0.04 mg氧-氯陰離子/公克組合物的包含二氧化氯之 組合物為實質上非細胞毒性的。 包含二氧化氣之實質上非細胞毒性組合物可使用具有中 性pH值之實質性純二氧化氣溶液來製備◎較佳,溶液具有 約5至約9 ’約6.5至約7.5之pH值。實質性純二氧化氯溶液 之一來源為使用在共同讓渡之美國專利第US 6,432,322號 及第 US 6,699,404 號中描述之 AESPTROL(BASF Corp.,Dm·Yi 52: 399-405). The acid selectively removes certain components of the tooth, thereby corroding the tooth surface by increasing surface area and surface roughness. Peroxides are known to have similar effects. Therefore, care needs to be taken to select polishing materials and techniques to balance the stain removal of each patient with the integrity of the tooth surface. There are currently three main types of abrasives for polishing teeth: phosphates, including orthophosphates, polymetaphosphates and pyrophosphates; carbonates; and cerium oxide. Aluminum telluride is also used as an abrasive. Abrasives can be found in both toothpaste formulations and prophylaxis pastes. The preventive paste is a product that is professionally used for polishing teeth by dental doctors and/or dental hygienists. Other abrasives include resin abrasive materials such as particulate wall products of urea and furfural, and those disclosed in U.S. Patent No. 3,070,5,10. Professional polishing includes a mechanically polished end 141702.doc 201113042 (mechanical polishing tip) driven by a low speed device (eg rubber cup or brush) and/or air polishing. The mechanically polished ends can be used alone or in combination with a preventive paste. Air polishing uses air, sodium bicarbonate, and water spray to remove stains and polish the teeth. In addition to the risk of improper dental grinding, some of the other problems with current professional polishing techniques include preventing splashing of the paste, discomfort caused by the frictional heat of the polished end, sensitivity of the tooth surface of the rot, and soft tissue. (including gums, tongue and lips) sensitivity to air polishing. In addition, air polishing is not advisable for patients with gingival or gingival pain. Chlorine dioxide (Cl〇2) is well known as a disinfectant and a strong oxidant. The bacteria, algicidal, fungicidal, bleaching and deodorizing properties of chlorine dioxide are also well known. Chlorine oxide (Cl〇2) is a chlorine-neutral compound in the +IV oxidation state and is sterilized by oxidation. However, it does not have chlorination. It is a relatively small, volatile and energetic molecule and is a free radical even in the form of a dilute aqueous solution. Chlorine dioxide acts as a highly selective oxidant due to its single electron transfer mechanism in the case where the dioxide is reduced to chlorite (Cl?2). At the pH ’, the PKa value of the sub-alcoholate ion/sub-acid balance is extremely low. This is not significantly equal to (10) the sub-gas/secondary acid ion pair equilibrium seen in the near-neutral condition, and indicates that the chlorite ion is present as a main substance in drinking water. One of the most important physical properties of chlorine dioxide is its high solubility in water, especially in cooling water. In contrast to the hydrolysis of chlorine in water, the second of the water: the chlorine does not hydrolyze at any significant extent' and remains in a dissolved state in the form of dissolved gases. 141702.doc 201113042 ^ The conventional method of preparing chlorine dioxide involves reacting sodium sulfite with gas i chlorine (Cl2(g)), hypochlorous acid (HOC1) or argonic acid (HC1). The reaction is: 2NaC102+Cl2(g)=2C102(g)+2NaCl [la] 2NaC102+H0Cl=2C102(g)+NaCl+Na0H [lb] • 5NaC102+4HCl=4C102(g)+5NaCl+2H20 [lc] The reactions [la] and [lb] are carried out at a greater rate in the acidic medium, resulting in an acidic product solution having a pH below 3.5 than substantially all conventional chlorine dioxide formation chemistry. Also, since the kinetics of the formation of chlorine dioxide is high in the concentration of the sulphonate anion, the chlorine dioxide formation is generally carried out at a higher concentration (> 1 〇〇〇 ppm), which must be diluted for use in The concentration used for the application. Chlorine dioxide can also be prepared from chlorate anions by a combination of acidification or acidification and reduction. Examples of such reactions include: 2NaC103+4HC1^2Cl〇2+Cl2+2H20+2NaCl [2a] 2HCl〇3+H2C2〇4^2Cl〇2+2C〇2+2H2〇[2b] 2NaC103+H2S04 + S02 2C102 + 2NaHS04 [2c] Under ambient conditions, all reactions require strong acidic conditions; most commonly in the range of 7-9 to N. Heating the reagent to a higher temperature and continuously removing chlorine dioxide from the product solution reduces the desired acidity to less than 1 N. The method of preparing the gas in situ uses a solution called "stabilized cerium oxide". The stabilized chlorine dioxide solution contains little or no di-rolled chlorine, but consists essentially of sodium chlorite at a neutral or weakly alkaline pH. 141702.doc 201113042 Adding acid to the sodium sulfite solution activates sodium sulfite and produces sulphur dioxide in situ in the solution. The resulting solution is acidic. Generally, sodium chlorite is converted to a lower level of oxidizing gas and a large amount of sodium chlorite remains in the solution. U.S. Patent No. 6,582,682 discloses an oral care composition comprising "environmental dioxide gas" which produces a dioxide gas upon exposure to a moderately acidic pH in the oral cavity. U.S. Patent No. 6,479,037 discloses the preparation of a chlorine dioxide composition for tooth whitening which is prepared by combining a chlorine dioxide precursor (CDp) moiety with an acidulant (ACD) moiety. The CDp portion is a metal chlorite solution having a pH greater than 7. ACD is acidic, for example having a pH of from 3 4.5 to 4.5. Apply CDP to the tooth surface. Acd is then applied to activate the metal chlorite and produce a dioxide gas. The value of 0 at the interface of the contact may be less than 6 and in another range of about 3.0 to 4.5 the resulting oxidizing gas composition on the surface of the tooth is acidic. In addition, this method may cause the cavity mucosa to be affected by contact with strongly highly acidic agents (ACD). U.S. Patent No. 6,432,387 discloses the generation of negative ions in the diaper, thereby effectively purifying the dental polishing agent in the case where the amount of abrasives and invasiveness is reduced. Dental Polishing Compositions However, there is still a need in the art to reduce side effects and methods. SUMMARY OF THE INVENTION The following summary of the invention is intended to be critical or to determine the following embodiments. Non-exhaustive overview. It is neither used to determine the various embodiments 141702.doc 201113042 Sexual Elements' does not describe its scope. A method of polishing a tooth surface is provided herein. The method comprises contacting a gingival surface with an effective amount of a polishing composition comprising a non-abrasive polishing agent, wherein the non-abrasive polishing agent comprises a oxidizing gas. In one embodiment, the composition is substantially non-cytotoxic. In certain embodiments, the polishing composition comprises less than about 0.2 mg of oxygen 'gas anion per gram of composition. In a consistent embodiment, the polishing composition comprises from about 5 to about 5% chlorine dioxide. In another embodiment, the polishing composition comprises from about 3 Torr to about 4 〇 p (iv) oxidizing air. In certain embodiments, the polishing composition has a positive value of from about 4.5 to about u. In other embodiments, the polishing composition has a pH of from about 5 to about, or a value of greater than about 6 and less than about 8. Some: In the example, the polishing composition may be a thick ancestor containing the thickener component, 'and & In certain embodiments of the sparse fluid composition, the thickener component is selected from the group consisting of natural water, semi-synthetic hydrocolloids, synthetic hydrocolloids = body bauxite. In the examples, the thickener component is a semi-colloid. An exemplary semisynthetic hydroquinone is methyl cellulose sodium. 3 Hard R Storm In some embodiments of the method, the contact of the #牙牙组合 reduces the degree. The surface roughness of the surface roughness is at least about less than the surface roughness of the tooth surface. In certain embodiments, the teeth are contacted with the composition without the hard tissue of the teeth; there is no substantial reduction (d) "microhardness; non-compliance reduces the microhardness of the dentin, and/or does not cause tooth sensitivity. ", In one embodiment, the composition is substantially non-irritating. In one implementation 141702.doc 201113042 Example 'The composition contacts the soft tissue of the mouth. In some embodiments, there is no need to protect the gums: in certain embodiments, the composition is optionally a mouthwash. In another aspect, a method of polishing a tooth surface is provided, the method comprising contacting a tooth surface with an effective amount of a composition comprising a non-abrasive polishing agent, wherein the non-abrasive polishing agent comprises chlorine dioxide and wherein the tooth surface is contacted The step causes substantial contact of the composition with the oral soft tissue. In one embodiment the composition is non-cytotoxic on the real f. In certain embodiments, the polishing core comprises less than 2 mg of oxygen chloride anion per gram of composition. In another embodiment the composition is substantially non-irritating. In a practical example, the polishing composition comprises from about 5 to about! Coffee Chong (7) Dioxide. In another embodiment, the polishing composition comprises from about 30 to about 40 ppm chlorine dioxide. In certain embodiments, the polishing composition has a positive value of from about seven to five U. In other embodiments, the polishing composition has a pH of from about 5 to about 9, or a value of greater than about 6 and less than about 8. In certain embodiments, the polishing composition can be a thickened fluid composition comprising a thickener component. In certain embodiments of the (iv) fluid composition, the thickener component is selected from the group consisting of natural hydrocolloids, semi-synthetic hydrocolloids, synthetic hydrocolloids. In the embodiment, the thickener component is a semi-synthetic water/body; the twin semi-synthetic hydrocolloid is a slow methyl cellulose, such as a slow methyl cellulose steel. In certain embodiments of the method, contacting the teeth with the composition reduces the surface roughness of the surface. The surface roughness can be reduced by at least about 5% compared to the table: roughness prior to contacting the tooth surface with the polishing composition. In a consistent example, contact between the tooth and the composition does not substantially damage the hard tissue of the tooth; it does not substantially reduce the microhardness of the enamel; it does not substantially reduce the microhardness of the tooth 丨 and / Or does not cause tooth sensitivity. 3 Shell In one embodiment, the composition is substantially non-irritating. In certain embodiments, the composition contacts oral soft tissue. In some embodiments, there is no need to protect the gums. In certain embodiments, the composition is optionally a mouthwash. A kit for preparing a dental polishing composition is also provided. The kit includes a first dispenser comprising a particulate precursor of chlorine monoxide; a second dispenser comprising a thickener component in an aqueous medium; and a preparation for oxidizing comprising an amount effective for tooth polishing A textbook of substantially non-cytotoxic compositions of chlorine. In one embodiment, at least one of the first dispenser and the second dispenser is a syringe. The thickener component can be selected from the group consisting of natural hydrocolloids, semi-synthetic hydrocolloids, synthetic hydrocolloids, and clays. In one embodiment, the thickened rhodium component is a semi-synthetic hydrocolloid. An exemplary semi-synthetic water swell is carboxymethyl cellulose 'such as sodium carboxymethyl cellulose. [Embodiment] For the purposes of the composition, the kit, and the method, only the % example is described in the drawings. However, the compositions, kits, and methods of use thereof are not limited to the precise arrangements and means of the embodiments described in the drawings. A method of polishing a tooth using a composition that does not include an abrasive is described herein. In another embodiment, the composition is non-cytotoxic and comprises a oxidizing gas. DEFINITIONS Unless otherwise defined, all technical and scientific terms used herein have the same meaning as 141702.doc -9- 201113042, which is generally understood by those of ordinary skill in the art. The nomenclature used herein and the laboratory procedures in cytopathic analysis, microbial analysis, organic and inorganic chemistry, and dental clinical studies are generally well-known and commonly used in the art for their nomenclature and laboratory procedures. As used herein, each of the following terms has the meaning associated with it in this section. The article "a" is used herein to refer to one or more of the grammatical terms of the article (ie, at least -). For example, “a factor” means an element or more than one element. The term "about" is to be understood to some extent by those of ordinary skill in the art and depending on the context in which it is used. In general, "about" is included as a range of values for the reference value +/_ ιο%. For example, "about 25%" includes a value of 27.5%. It should be understood that all integers or partial integers between any ranges of M in this document are included. Its dihydrate. As used herein, "polishing" is used to refer to the treatment of a tooth surface to achieve the following: one method: reducing surface roughness (equivalent to increasing surface smoothness); removing foreign soiling; and removing plaque. "Surface roughness" as used in 槿Π文I refers to the microscopic formation of the tooth surface, and the h surface roughness can be measured according to several parameters known in the art. Not limited to) average surface roughness Ra, · q (also known as RMS; root mean square rough seam) ^^ 0 'Kt (the largest rough on the surface of the sample), called the average maximum peak height;) Maximum surface thickness _ 141702.doc 201113042 degrees). The surface roughness can be measured based on the average surface roughness Ra. (10) The arithmetic mean return of the irregularity of the coarse component of the midline measured over the length of the sample. The k small Ra value indicates a smoother surface. The surface thick chain can be used for the promotion of β by the art. 4 7 ^ Any method used to measure Ra (such as surface profile measurement, face scan method, and atomic force microscopy) to measure. The surface roughness can be measured after at least a treatment period and before any subsequent substantial exposure to other substrates, such as remineralization solutions (including saliva). "Grinding" as used herein refers to a substance that is abraded by foreign materials or objects such as green enamel or dentin. As used herein, "abrasive" is a compound or material that can be used to mechanically grind dental materials. As used herein, "shoulder button" refers to the chemical intrusion of the surface of the tooth caused by acid (exogenous and/or endogenous) and/or chelating agents acting on the surface of the tooth. 0 As used herein, "non- An abrasive polishing agent refers to any compound, or combination of compounds, that can quantitatively reduce the surface finish of a tooth without mechanical grinding. Exemplary non-abrasive polishes can also be non-corrosive. "Chemical polishing as used herein" refers to polishing using a non-abrasive polish. As used herein, "effective amount" of a polishing agent is used to mean any amount of polishing agent that will result in polishing the surface of the tooth by one or more treatments. The effective amount is the amount that results in a reduction in the surface roughness of the tooth. As used herein, "cytotoxicity" refers to the property of causing a fatal injury to the structure or function of a mammalian fine monthly package. #当活性医药成分141702.doc -11 - 201113042 (API) When the effective amount is present, the composition meets USp<87> "in vitro bioreactivity" agar diffusion test (currently approved in 2007) The United States Pharmacopeia (USP) bioreactivity limit considers the composition to be "substantially non-cytotoxic" or "non-substantially cytotoxic". As used herein, "irritation" refers to an I" biomass that causes a local inflammatory response (such as redness, swelling, itching, burns, or wraps) by immediate, prolonged or repeated exposure. The composition is considered to be "substantially non-irritating" or "non-substantially irritating" if it is determined to be mild or non-irritating by any standard method of doubling oral mucosal irritation. Non-limiting examples of such methods include: HET_CAM (egg test 'woven chorioallantoic membrane); 输 transmucosal stimulation (4); and in vitro testing using weiwei oral mucosa. As used herein, "dental hard tissue" refers to at least one of sorghum and dentate. As used herein, "dental hard tissue damage" means at least one of the following: a decrease in the microhardness of the enamel and a decrease in the microhardness of the dentine. As used in this =, if the following - or more are satisfied, the composition does not "Bevow knows the hard tissue of the tooth":]) The microhardness reduction of the tannin is less than about 15% ' and / or at 5% At the level, the reduction is not statistically significant; and 2) the reduction in microhardness of the dentin is less than about 15%, and/or at ice trust levels, the reduction is not statistically significant. The term "oxy-chlorine anion" as used herein refers to chlorite ((10)2·) and/or chlorate (cio3·) ions. 141702.doc 201113042 As used herein, "substantially pure chlorine dioxide solution" means a solution of chlorine dioxide having a non-cytotoxic concentration of an oxy-chlorine anion. A solid sulfur dioxide solution as used herein also refers to a concentrated solution of chlorine dioxide containing a concentration of an oxy-chlorine anion which, after dilution to an effective amount of chlorine dioxide, is related to the oxy-chlorine anion. It is not cytotoxic in terms of indifference. The phrase "slightly fluid composition" encompasses compositions which are capable of flowing under the applied shear stress and which, when flowing, have an apparent viscosity greater than the viscosity of the corresponding aqueous chlorine dioxide solution of the same concentration. This includes a full range of expelling fluid compositions comprising: a fluid exhibiting Newtonian flow (wherein the ratio of shear rate to shear stress is ^ and the shearing force of the viscous disk is independent), and the shearing is reduced Viscous fluids (which need to overcome the minimum yielding shore force before flowing, and which also exhibit thinning as the shear continues), pseudoplastic and plastic fluids (which need to overcome the minimum yield stress before flowing), Pressurized (iv) fluid composition (which increases with the trim rate) and other materials that can flow under the applied yield stress. As used herein, the phrase "thickened" and "parts" means A component having the property of thickening the addition of the potting solution or mixture. The "slightening agent component" is used to prepare the "thickening fluid composition" as described above. - The short apparent viscosity is defined as The ratio of the shear stress to the shear rate of any shear condition that causes the flow. The apparent viscosity t shear stress is irrelevant for the material fluid and the apparent viscosity versus shear rate for non-Newtonian fluid compositions. And change. In this article The term "microparticles" is used to refer to all solid materials. As a non-141702.doc •13·201113042 limiting it example, the microparticles may be interspersed with each other to contact each other in some way. These solid materials include particles of any size, and Combinations of Particles of Different Sizes Description The compositions, kits, and methods of use described herein are derived in part from the contact of a tooth surface with a chlorine dioxide composition to minimize damage to soft and hard tissues of the teeth. To a lesser extent, the surface of the tooth is reduced in thickness. In particular, at a 5% confidence level, the oxidized chlorine composition reduces the average surface roughness of the enamel at a statistically significant level. In some embodiments, The chlorine dioxide composition can be non-cytotoxic and/or non-irritating. In some aspects, the surface roughness of the tannin is reduced by at least about 5%, or at least about 8 compared to the surface roughness prior to treatment. %, or even at least about 10%. In one embodiment, the average surface roughness of the enamel is reduced by at least about 12% compared to the average surface roughness prior to treatment. In the meantime, the average surface roughness of the dentate is not increased by a statistically significant amount. The non-cytotoxic and non-irritating chlorine dioxide-containing composition on the sputum is advantageously not adversely affected to a significant extent. Hardness, and therefore does not substantially damage the hard tissue of the teeth. Thus, in one aspect, a method of chemically polishing a tooth is provided. In particular, the method comprises combining a tooth surface with an effective amount of substantially non-cytotoxicity Contact, wherein the composition comprises a polishing agent that polishes the surface of the contact window that is contacted without mechanical grinding. Advantageously, the method is not required to polish the end or spray water. Thus, when using the combinations described herein In the case of objects, kits and methods, avoid the improper use of these appliances 141702.doc -14- 201113042. In addition, one type is particularly suitable for teeth with corroded enamel and / or tel mussels and exposed Quality patient approach. Compared to tannins, the dentin is more sensitive to grinding and is believed to form the basis of tooth sensitivity. Therefore, non-abrasive polishing methods are expected to maintain the structural integrity of the tooth and thereby minimize the risk of developing tooth sensitivity. I. Composition The composition for carrying out the method is an aqueous fluid comprising a non-abrasive polish, wherein the polish is chlorine dioxide. In other embodiments, the compositions can be substantially non-cytotoxic, substantially non-irritating, and combinations thereof. In certain embodiments, the composition comprises a thickener component that renders the composition a thickened aqueous fluid. In other embodiments, the composition can be a mouthwash that can remain in the mouth, in contact with the teeth and soft tissue. Compositions suitable for use in the process comprise at least about 5 ppm, or at least about 20 ppm' or even at least about 3 ppm of chlorine dioxide. Generally, the amount of chlorine dioxide can be up to about 1 〇〇〇 ppm, or up to about 7 〇〇, or up to about 500 ppm, or up to about 2 〇〇 ppm. In certain embodiments, the concentration of dioxin is in the range of from about 5 to about 700 ppm' or from about 20 to about 5 ppm, or from about 30 to about 200 ppm dioxide. In one embodiment, the composition comprises from about 30 to about 40 ppm chlorine dioxide. In one embodiment, the composition comprises about 30 PPm. In another embodiment the composition comprises about 40 ppm. Soft tissue stimuli can be produced by highly reactive oxygen species such as those found in peroxidate-based compositions. Soft tissue stimulation can also result from pH extremes of both acidic and basic. In order to minimize the stimulation of soft tissue by the chlorine dioxide-containing composition, the substance is substantially non-cytotoxic. 141702.doc -15· 201113042 ^The compound has at least about 3 5 women. To reduce the potential for hard surface cooking, the composition has a positive value of at least about 4.5. The composition may have a pH of up to about 5 ′ J' and more preferably greater than about 6. In certain embodiments, the pH is in the range of from about 4.5 to about 11, more preferably from about 5 to about 9, and more preferably greater than about 6 and less than about 8. In an embodiment, the pH is from about 6.5 to about 75. Salty stimulation is not caused by the concentration of oxygen and chloride anions. Because the composition can be substantially non-irritating, there is no need to protect the chiseled silver or other soft tissues from irritation prior to treatment. For a composition comprising a oxidizing gas as shown herein ♦, cytotoxicity is primarily produced by the oxygen-gas anion present. Thus, in the absence of other components which cause cytotoxicity, it comprises from 〇 mg (mg) of oxygen-gas anion per gram of composition to no more than about 11 25 11 ^ oxygen-gas anion / gram of composition 'better 0 To about 〇·24, 〇.23, 〇·22, 〇21 or 〇2 〇 oxygen/gas anion/gram composition, more preferably from 0 to about 0.19, 0.18, 〇.17, (M6 〇·15, 〇 ·ΐ4, 0.13 '0.12, 〇·11 or 〇.1〇„^ oxygen_chlorine anion/gram composition, and more preferably 0 to about 〇〇9, 〇〇8, 〇〇7, 〇〇6, 0.05 or The chlorine dioxide-containing composition of 0.04 mg of the oxygen-chlorine anion per gram of composition is substantially non-cytotoxic. The substantially non-cytotoxic composition comprising the oxidizing gas can be substantially purely oxidized with a neutral pH. Preferably, the solution has a pH of from about 5 to about 9 'about 6.5 to about 7.5. One source of substantially pure chlorine dioxide solution is used in US Patent No. 6,432,322 and US AESTROL (BASF Corp., described in 6,699,404

Florham Park, NJ)製備的二氧化氯》此等專利揭示的固體 141702.doc -16- 201113042 二添加至時可製備高度轉化之二氧化氣溶液。固體包 、 氯馱鹽(諸如亞氣酸鈉)、酸來源(諸如硫酸氫鈉) 及視丨“兄選用之游離齒素來源(諸如二氯異氰尿酸之納鹽 或其水合物)。aspetr〇l材料提供在實質上中性pH值下 有效地生成二氧化氣之方法,因此避免較早以二氧化氣為 主之m 口腔產品所存在之牙齒相容性問題。水性流體中 ^aseptrgl材料具有極高轉化率,產生高濃度之二氧化 氯及低濃度之氧-氯陰離子。 制製備實質性純二氧化氯之另一方法為藉由任何已知方法 衣備一氧化氣源溶液,隨後使空氣鼓泡^ ^ ^ ^ ^ ^ 且進入去離子水之第二容器,從而製備實質性純== 產物/合液僅ci〇2及可能某些水蒸氣自源溶液轉移至產 物溶液。所有鹽成份仍保留於源溶液令。因此,實質性純 產物溶液中不存在氧-氯陰離子。雖然二氧化氯可能會進 行-定程度之分解’但速率相當緩慢。藉由保持溶液加蓋 及避免曝露到紫外線,可使分解速率減慢至7天中二氧化 氯降低約5至約25%之速率。實質性純二氧化氣亦可使用 全瘵發技術(諸如揭示於美國專利第4,683,039號中之彼技 術)製備。另外,金屬亞氯酸鹽及酸來源可在溶液狀態下 反應,獲得轉化成為二氧化氣之較高轉化率且產生大於约 2000 Ppm二氧化氯溶液。可隨後將濃溶液緩衝至中性?11 值。類似地,美國專利第5,399,288號中描述之组合物可製 備一氛化氯溶液’該組合物在酸性pH值下獲得高濃度二氧 化氯溶液。可隨後將濃溶液緩衝至實質上中性pH值,從而 141702.doc 17 201113042 製備實質性純二氧化氯溶液。 可使用熟習此項技術者已知之任何方法量測此等溶液 中之氧-氯陰離子,該等方法包括遵循EPA測試方法300 之一般程序之離子層析法(Pfaff,1993, 「Method 300.0Chlorine dioxide prepared by Florham Park, NJ) Solids 141702.doc -16 - 201113042 disclosed in these patents can be used to prepare highly converted dioxide gas solutions. A solid package, a chlorinated salt (such as sodium sulfite), an acid source (such as sodium bisulfate), and a source of free dentate selected by the brother (such as a sodium salt of dichloroisocyanuric acid or a hydrate thereof). The 〇l material provides a method for efficiently generating oxidizing gas at a substantially neutral pH value, thereby avoiding the problem of tooth compatibility in the earlier oral gas products mainly composed of oxidizing gas. The ^aseptrgl material in the aqueous fluid It has a very high conversion rate, and produces a high concentration of chlorine dioxide and a low concentration of oxygen-chlorine anion. Another method for preparing substantially pure chlorine dioxide is to prepare a solution of a source of oxygen gas by any known method, and then to make Air bubbling ^ ^ ^ ^ ^ ^ and entering the second container of deionized water to prepare substantially pure == product / liquid only ci 〇 2 and possibly some water vapor transferred from the source solution to the product solution. All salts The composition remains in the source solution. Therefore, there is no oxygen-chlorine anion in the substantially pure product solution. Although chlorine dioxide may undergo a certain degree of decomposition, the rate is rather slow. By keeping the solution capped and avoiding exposure Ultraviolet light can slow down the rate of decomposition to a rate of about 5 to about 25% reduction in chlorine dioxide over 7 days. Substantially pure dioxide gas can also be used in full burst technology (such as the technology disclosed in U.S. Patent No. 4,683,039 In addition, the metal chlorite and acid source can be reacted in a solution state to obtain a higher conversion rate of conversion to dioxide gas and produce a chlorine dioxide solution of greater than about 2000 Ppm. The concentrated solution can then be buffered to medium A composition of the composition described in U.S. Patent No. 5,399,288, which is capable of producing a concentrated chlorine solution. The composition obtains a high concentration of chlorine dioxide solution at an acidic pH. The concentrated solution can then be buffered to substantial Upper neutral pH, thus 141702.doc 17 201113042 Preparation of a substantially pure chlorine dioxide solution. Oxygen-chlorine anions in such solutions can be measured using any method known to those skilled in the art, including adherence to EPA testing Method 300 of general procedure for ion chromatography (Pfaff, 1993, "Method 300.0

Determination of Inorganic Anions by Ion Chromatography」 Rev. 2.1,美國環境保護局(U.S· Environmental Protection Agency)),或基於電流測定方法之滴定法(Eaton等人編 「Standard Methods for the Examination of Water and Wastewater」第1 9版,美國公共衛生協會(American Public Health Association), Washington DC, 1995 中之電流測定方 法II)。或者,氧-氯陰離子可藉由與電流測定方法等效之 滴定技術,但改將碘化物氧化成為碘,且隨後以硫代硫酸 鈉滴定至澱粉終點,代替電流滴定法量測;此方法在本文 中稱為「pH 7緩衝滴定法」。可自一般經假定包含約80重 量%之純亞氣酸鈉之工業級固體亞氯酸鈉製備亞氯酸鹽分 析標準物。 為製備實質上非細胞毒性、非刺激性且不損傷牙齒硬組 織之包含二氧化氣的稠化水性組合物,可隨後使實質性純 二氧化氯溶液與稠化劑組份及水性介質組合。因此,另一 實施例包涵雙組份式拋光系統,其包含包括實質性純二氧 化氯溶液之第一組份及包括水性介質中之稠化劑組份之第 二組份。第一及第二組份之組合獲得包含有效用於牙齒拋 光之量之二氧化氣的非細胞毒性組合物。在溶解狀態下之 二氧化氯隨時間分解。為避免由該分解產生之問題(包括 141702.doc -18- 201113042 功效損失及生成亞氣酸根陰離子),冑質性純二氧化氮溶 液可在其㈣化劑組份及水性介f組合之前即刻製備。另 外’該組合物可在其用於該方法中之前即刻製備。如本文 中所用之「在…之前即刻」係指比引起削弱之功效或細胞 毒性跡象的彼時間短的時間。通常,「在…之前即刻」可 小於約14天’且不大於約24小時,1更佳不大於約2小 柃。實質性純二氧化氯溶液可在製備組合物之約8小時内 製備。亦保持謹慎以避免二氧化氣溶液或所製備之組合物 曝露於強紫外光或高溫(例如大於環境溫度(約25。〇)之温 度)。 製備包含二氧化氯之實質上非細胞毒性稠化組合物之方 法亦揭示於2009年2月6日申請之名為「N〇n_Cyt〇t〇xicDetermination of Inorganic Anions by Ion Chromatography" Rev. 2.1, US Environmental Protection Agency, or titration based on current measurement methods (Eaton et al., "Standard Methods for the Examination of Water and Wastewater" Version 19, American Public Health Association, Washington DC, 1995, Current Measurement Method II). Alternatively, the oxy-chlorine anion can be oxidized to iodine by a titration technique equivalent to the current measurement method, but then titrated to the starch end point with sodium thiosulfate instead of current titration; This is referred to as "pH 7 buffer titration". The chlorite analytical standard can be prepared from industrial grade solid sodium chlorite, which is generally assumed to contain about 80% by weight of pure sodium sulfite. To prepare a thickened aqueous composition comprising a dioxide gas that is substantially non-cytotoxic, non-irritating and does not damage the hard tissue of the teeth, the substantially pure chlorine dioxide solution can then be combined with the thickener component and the aqueous medium. Accordingly, another embodiment encompasses a two-component polishing system comprising a first component comprising a substantially pure chlorine dioxide solution and a second component comprising a thickener component in an aqueous medium. The combination of the first and second components results in a non-cytotoxic composition comprising a quantity of oxidizing gas effective for tooth polishing. The chlorine dioxide in the dissolved state decomposes over time. In order to avoid the problems caused by this decomposition (including 141702.doc -18- 201113042 loss of efficacy and formation of nitrous acid anions), the phthalic pure nitrogen dioxide solution can be prepared immediately before the combination of its (four) chemical component and aqueous media . Further, the composition can be prepared immediately before it is used in the process. As used herein, "immediately before" refers to a period of time that is shorter than the time causing impaired efficacy or signs of cytotoxicity. Generally, "immediately before" may be less than about 14 days' and no more than about 24 hours, and more preferably no more than about 2 hours. Substantially pure chlorine dioxide solution can be prepared within about 8 hours of preparing the composition. Care is also taken to avoid exposure of the dioxide gas solution or the prepared composition to strong ultraviolet light or high temperatures (e.g., temperatures greater than ambient temperature (about 25 Torr)). A method of preparing a substantially non-cytotoxic thickening composition comprising chlorine dioxide is also disclosed as "N〇n_Cyt〇t〇xic" filed on February 6, 2009.

Chlorine Dioxide Fluids」之共同讓渡美國臨時專利申清案 第61/^,685號中,該參考案之全文以引用的方式併入本 文中。 製備包含二氧化氯之稠化組合物之方法亦揭示於(例如) 共同讓渡之美國專利公開案第2〇〇6/〇169949號及第 2007/0172412號中。在實施此等兩個公開案中描述之方法 時,必須採取步驟(如本文中描述)來控制氧_氯濃度以便產 生非細胞毒性組合物。 包含二氧化氯之實質上非細胞毒性組合物亦可使用^… 之微粒前驅體及水性稠化流體組合物來製備。因此,亦涵 盍雙組份式拋光系統,其包含包括二氧化氯之微粒前驅體 之第一組份及包括含於水性介質中之稠化劑組份之第二組 141702.doc -19· 201113042 份。第一及第二組份之組合獲得包含美白牙齒有效量之二 氧化氣的非細胞毒性組合物。C102之前驅體包括金屬亞氯 酸鹽、金屬氯酸鹽、酸來源,及視情況選用之鹵素來源。 微粒前驅體可包含此等前驅體中之一者或此等前驅體之任 何組合。例示性微粒前驅體可為ASEPTROL產品,諸如 ASEPTROL S-Tab2。ASEPTROL S-Tab2 具有以重量計之以 下化學組成(%) : NaC102 (7%) ; NaHS04 (12%) ; NaDCC (1%) ; NaCl (40%) ; MgCl2 (40%)。美國專利第 6,432,322 號之實例4描述S-Tab2之例示性製造方法。隨後藉由粉碎 經壓縮之S-Tab2錠劑或由S-Tab2組份之未經壓縮之粉末乾 式滾轉壓實,接著使所得經壓實之條帶或磚塊分解,且篩 分獲得所需大小,產生顆粒。在曝露於水或水性稠化流體 後,自ASEPTROL顆粒生成二氧化氯。在一實施例中,藉 由將約40篩目顆粒與水性稠化流體組合,製備包含二氧化 氯之實質上非細胞毒性組合物。在一態樣中,稠化流體之 稠化劑組份為羧曱基纖維素。水性稠化流體可在與 ASEPTROL顆粒組合之前充份製備,使稠化劑組份能夠完 全水合。在一實施例中,稠化流體組合物藉由將高黏度 NaCMC粉末添加至蒸餾水來形成。可使NaCMC水合至少 約8小時,且隨後可攪拌混合物,使其均質化。可隨後藉 由使經篩分之ASEPTROL顆粒與NaCMC稠化流體組合物混 合,製備用於牙齒拋光之實質上非細胞毒性組合物。 稠化流體組合物亦可原位形成,其中以唾液作為水性介 質。在一實施例中,可(例如)藉由添加有延展性之堪來使 141702.doc -20- 201113042 ASEPTROL顆粒與稠化劑組份之混合物塑成型,且隨後將 忒形狀訑加於牙齒。唾液活化顆粒,形成二氧化氣及稠化 劑組份水合物,從而於原位形成稠化流體組合物。在另一 貫她例中可將ASEPTR0L顆粒及稠化劑組份之混合物置 放於牙用條帶或牙用薄膜上或置放於牙托中。牙用條帶係 指由具有足夠撓性以附著於牙齒上之塑性骨架製成之實質 上平面物虹。牙用薄膜係指由可實質上配合牙齒表面之可 ¥性、適型忖料製成之實質上平面物體。視情況,牙用條 帶可溶解於水性介質(諸如唾液)中。將條帶、薄膜或牙托 安置於牙齒上,且唾液充當如上所述之水性介質,於原位 產生稠化流體組合物。或者,條帶或牙托上之混合物在安 置於牙齒上之前先與水或水性介質接觸。 不存在直接量測稠化流體組合物中之氧_氯陰離子之極 精確方法。然而,可藉由量測水溶液中之氧_氯陰離子(在 稠化之前)’且基於最終稠化流體之重量來調整最終濃度 而精確地估此值。預期本文中其它地方描述之滴定法適 用於評定稠化流體組合物令之二氧化氯濃度及氧'氯陰離 子濃度兩者。預期可使用如本文中其它地方描述之離子層 析法量測稠化流體組合物中之氧_氯陰離子,其限制條件 為採取步驟以預防水合稠化劑組份污染管柱。—該種步驟 為使用分子量過渡器以在施加於層析管柱之前移除水合稍 化劑組份(諸如水合CMC)。若需要,稍化流體組合物可在 分析之前以水稀釋以降低其黏度或以其他方式使其更易於 測试。熟習此項技術者可易於藉由使用usp<87>2壤脂擴 141702.doc 201113042 散測試之USP生物反應性限度來判定調配物是否具有細胞 毒性而憑經驗判定指定調配物是否具有足夠低之氧-氯濃 度。 用於實施該方法之水性稠化流體組合物可包含水性介質 中之任何稠化劑組份,其中稠化流體組合物對於軟組織 (尤其口腔黏膜)為非細胞毒性及非刺激性的,且對硬組織 (諸如琺螂質及齒質)造成最低程度之損傷。另外,在組合 物製備及用於處理中之時間標度下,稠化劑較佳不受拋光 劑的有害影響。許多稠化劑在此項技術中為已知的,包括 (但不限於)卡波姆(carbomer)(例如CARBOPOL稠化劑, Lubrizol Corp., Wickliffe, OH)、羧曱基纖維素(CMC)、乙 基纖維素、羥乙基纖维素、羥丙基纖維素、天然蒙脫石黏 土(例如 VEEGEM,R.T. Vanderbilt Co.,Norwalk, CT)、合成 黏土(例如 LAPONITE(Southern Clay Products,Gonzales, TX))、甲基纖維素、超級吸附聚合物(諸如聚丙烯酸酯(例 如 LUQUASORB 1010, BASF,Florham Park,NJ))、泊洛沙 姆(poloxamer)(PLURONIC,BASF,Florham Park, NJ)、聚 乙稀醇、海藻酸鈉、黃蓍勝及三仙膠(xanthan gum)。該等 稠化劑可分類為四組:天然水膠體(亦稱為「膠」)、半合 成水膠體、合成水膠體及黏土。天然水膠體之某些實例包 括阿拉伯膠(acacia)、黃蓍膠、海藻酸、角叉菜膠、刺槐 豆膠、瓜爾膠(guar gum)及明膠。半合成水膠體之非限制 性實例包括曱基纖維素及羧甲基纖維素鈉。合成水膠體 (亦稱為「聚合物」’包括聚合物、交聯聚合物及共聚物)之 141702.doc -22- 201113042 某些實例包括聚丙烯酸酯、超級吸附聚合物、高分子量聚 乙二醇及聚丙二醇、聚氧化乙烯及CARBOPOL。黏土(包 括膨脹黏土)之非限制性實例包括LAPONITE、綠坡縷石 (attapulgite)、膨潤土(bentonite)及 VEEGUM。例示性稠化 劑組份可為半合成水膠體。稠化劑組份亦可為高黏度羧甲 基纖維素鈉(NaCMC粉末)。 CMC為羧甲基(-CH2-COOH)與構成纖維素骨架之葡萄哌 喃糖單體之某些經基結合之纖維素衍生物。其藉由纖維素 與氯乙酸之鹼金屬催化反應來合成。極性(有機酸)羧基使 纖維素具有可溶性及化學反應性。CMC之功能性質視纖維 素結構之取代度(亦即已參與取代反應之羥基之數目)及纖 維素骨架結構之鏈長度而定。 可獲得一系列黏度等級且符合USP標準之CMC。在25°c 下、在水中為1%濃度下,高黏度CMC(諸如來自Spectrum Chemical Manufacturing Company之CA194型)具有介於約 1500與3 000 cps之間的黏度。 一種組合物呈流體形式。在某些實施例中,流體可為具 有適合於將流體施加於牙齒表面且在牙齒拋光處理之持續 時間(例如約5至約60分鐘)内將流體保持在適當位置之流動 性質的稠化流體。因此,具有當施加於牙齒時足以保持其 形狀但足夠低以便易於藉由擦拭而移除之屈服點的假塑性 組合物在實施該方法時可為有利的。在使用牙托、條帶或 類似裝置使組合物接觸牙齒的實施例中,組合物應具有足 夠黏著力以將裝置保持在適當位置。例示性黏著劑揭示於 141702.doc -23- 201113042 美國專利公開案第2008/0025925號中。 用於該方法中之組合物可視情況包含其他組份。在某些 實施例中,組合物不包括任何研磨性組份。在其他實施例 中,組合物可含有次有效量之研磨性組份。在此等實施例 中’研磨性組份之量實質上少於有效量。「實質上少於」 意謂至少約25%少於研磨劑之有效量,或至少約5〇%少於 有效量’或至少約75%少於有效量。在此項技術中已知之 研磨劑組伤包括一氧化石夕;硼石夕酸玻璃片晶;碟酸鹽,包 括正碌酸鹽、聚偏磷酸鹽及焦磷酸鹽;碳酸鹽,諸如碳酸 氫納及碳酸鈣(白堊);樹脂研磨材料;及氧化鋁。在其他 實施例中,組合物含有實質上少於在不存在二氧化氯的情 況下用於拋光所需量之有效量的研磨劑組份。亦即,預期 指定量之研磨劑之拋光功效可藉由包含二氧化氯及少於, 且較佳达少於指定量之量之研磨劑組份的組合物達成。雖 然在此等實施例中將發生機械研磨’但是預期歸因於組合 物中之機械研磨劑之量降低,機械研磨處於實質上降低之 水準’同時仍達成牙齒拋光。 可存於組合物中之其他視情況選用組份包括(但不限於) 甜味劑、調味劑、著色劑及芳香劑。甜味劑包括糖醇。例 示性糖醇包括山梨糖醇、木糖醇、乳糖醇、甘露糖醇、麥 芽糖醇、氫化澱粉水解產物、赤藻糖醇、還原巴糖 (reducing paratinose)及其混合物。調味劑包括(例如)天然 或合成精油(essential oil)以及各種調味醛、g旨、醇及其他 材料。精油之實例包括綠薄荷油、胡椒薄荷油、冬青油、 141702.doc •24· 201113042 再樟油、丁香油、鼠尾草油、按樹油、馬郁籣油、肉桂 油' 檸檬油、萊姆(lime)油、葡萄柚油及橙油。著色劑包 括由管理機構批准用於併入食品、藥品或化妝品中之著色 劑’諸如由FDA批准在美國使用之FD&C或D&C顏料及染 料。芳香劑包括薄荷腦、乙酸薄荷酯、乳酸薄荷酯、樟 月尚、桉樹油、桉油醇、大茴香腦、丁香酚、桂皮、二氡雜 %己二嗣(oxanone)、α_紫羅蘭酮、丙烯基癒創木酚、瑞香 草酚、沉香醇、苯甲醛、肉桂醛、Ν_乙基-對-薄荷烷小甲 醯胺、Ν,2,3-二甲基-2-異丙基丁酿胺、3-(1-曱氧基)_丙烧_ 1,2-二醇、肉桂醛甘油縮醛(CGA)、薄荷酮甘油縮醛 (MGA)及其類似物。 組合物之其他視情況選用組份包括:抗細菌劑(除二氧 化氯之外)、酶、惡臭控制劑(除二氧化氯之外)、清潔劑 (諸如磷酸鹽)、抗齒齦炎劑、抗牙菌斑劑、抗齒垢劑、抗 齲齒劑(諸如氟離子來源)、抗牙周炎劑、營養物、抗氡化 劑及其類似物。例示性藥劑在此項技術中為熟知的。例如 參見美國專利公開案第2005/0287084號、第2〇〇6/〇2633〇6 唬、第 2007/0259011 號及第 2008/0044363號。 較佳所有視情況選用之組份具有針對藉由二氧化氣之氧 化的相對抗性,此歸因於組合物組份藉由二氧化氯氧化會 減少可用於拋光牙齒表面之二氧化氯〆 在製備含有二氧化氯之組合物及在方法中使用含 氯之組合物之時間標度中,視情況選用組份之功能不备為 到實質性削弱且組合物保持其拋光功效。組合物亦仍^ 141702.doc -25- 201113042 質上非細胞毒性的、實質上非刺激性的,且不會實質性損 傷牙齒硬組織。 Ι][·使用方法 j中1操作法為由牙齒表面與组合物接觸,該組合物 包含有效量的的拋光劑,在無需機械研磨的情況下即可抛 斤接觸之牙齒表面。該組合物可為且應為實質上非細胞 I生及非刺激性。與牙齒接觸以達成可量測之牙齒抛光程 ^持續時_容易由熟習此項技術者依據本文中之教示 疋。有利地,甚至在長期接觸之後,組合物亦不會實質 性損傷牙齒硬組織。雖然接觸可長達至多16、17、18、19 或分鐘,或另外長達至多約mum 2:、28、29或30分鐘,或另外至多約H 45、50、55 二:刀鐘或在某些情況下更長範圍之時間’但接觸持續時 間一般在數秒至數分鐘之範圍内,至少^5、3()、45_ 秒,至少約1、2、1 /1斗、r、 勺 3、4或5分鐘,約6、7、8、9或10分 * 12 13、14或15分鐘。在某些實施例中,接觸 持、,時間在介於約丨與約6〇分鐘之間的範圍 :至約3〇分鐘,且更佳㈣至㈣分鐘。在另一實施: 用於處理之接觸持續時間可為約15分鐘。處理頻率亦 =易由知悉本揭示案之熟習此項技術者確定。該處理可 包括一次牙齒接觸過程或-次以上。處理次數可為連續、 在間隔時間上(例如幾小時至幾天,幾天至幾週,以及包 括數月至一年或-年以上之更長時間間隔)或兩者。 組合物與牙齒表面之間的接觸可藉由若干在此項技術中 141702.doc -26 · 201113042 热知之方法_之任一者達成。可將組合物刷拭或塗抹於牙 齒表面上。可將組合物噴灑或起泡溢於牙齒表面上。組合 物可存在於撓性條帶或貼片上,該條帶或貼片可施壓於且 模£於牙齒表面。組合物可用作漱口水;因此,可將組合 物保持於口令且使其靜態地,或伴以使用(例如)舌及煩在 口内攪動而接觸牙齒。可將組合物置放於牙托中,隨後可 將牙托以與牙齒接觸之方式置放。該等牙托可定製或非定 製。適用於實施該等方法之許多裝置揭示於此項技術令, 包括(但不限於)美國專利第5,879,691號、第6,55 1,579號、 第 6,682,721 5虎、第 6,848,9〇5 f虎、第 6,896,518 號、第 6,964,571號、第7,Q()4,756號、第7,㈣,897號美國拳利 a 開案第 2006/0223033 號、第 2007/0298380 號及第 2008/00259255虎,及國際專利公開案第pCT/US2〇〇6/〇6i〇9 號。此等參考案中之每一者之全文以引用的方式併入本文 中。 在某些實施例中,可使用牙托實施該方法。在一態樣 中’牙托為定製的。製造定製牙托的方法在此項技射為 熟知的;例如參見美國專利第6,1〇6,284號及第M25,759號 及美國專利公開案第2〇〇6/〇183〇8〇號及第2〇〇_4_ 號。此等參考案中之每一者之全文以引用的方式併入本文 卜簡言之’印模牙托以印模材料(諸如海藻酸鹽)填充。 隨後將印财托安置於患者口巾以便在㈣材料中產主牙 齒之陰性印模。在已形成陰性印模之後,將印模牙托尹產 生之陰性印模以軟鑄造材料(諸如牙科用硬質石膏(d論i 141702.doc -27· 201113042 st〇ne)、石膏或環氧樹脂)填充。隨後將印模牙托翻轉且安 裝於預成也安裝裝置(諸如牙齒鱗造托盤或底座)上。在鎮 &材料有機會硬化之後,將印模牙托移除以使得鑄造材料 在安裝表面上形成陽性牙齒印模。製備定製牙托之另一方 法「利用沸騰及》父合」材料,其由諸如乙烯乙酸乙烯酯 \ y Vlnyl aeetate ’ EVA」)或聚乙婦之可熱成型塑膠 衣成疋衣牙托可藉由在彿水中加熱可熱成型塑膠,使其 在生物學上可接受之、θ Λ 〈舰度下熗融,且隨後直接將其置放於 個體之牙齒上,盆於牙告l、人,、 '、牙齒上冷部且保持其新形狀而產生。 為貫施該方法,將&各非& 3非研磨性拋光劑之實質上非細胞毒 性組合物置放於牙托中。 ψ 隨後將牙托安置於患者口中以便 於處理事件。 亦預期可藉由使軟組織與存在於組合物中之氧-氯陰離 :之接觸降至最低程度或預防軟組織與存在於組合物中之 乳-氯陰離子之接觸而使得二氧化氯組合物之投與實質上 為1Μ田胞毒性的。因此,作為-實例,設想包含可讓二氧 化鼠透過,實質上不讓氧_氯陰離子透過之微孔性障壁的The co-transfer of US Provisional Patent Application No. 61/^, 685, the entire contents of which is incorporated herein by reference. A method of preparing a thickened composition comprising chlorine dioxide is also disclosed in, for example, U.S. Patent Publication No. 2/6/169949 and No. 2007/0172412. In carrying out the methods described in these two publications, steps (as described herein) must be employed to control the oxygen-to-chlorine concentration to produce a non-cytotoxic composition. Substantially non-cytotoxic compositions comprising chlorine dioxide can also be prepared using particulate precursors and aqueous thickening fluid compositions. Accordingly, a two-component polishing system comprising a first component comprising a particulate precursor of chlorine dioxide and a second component comprising a thickener component contained in an aqueous medium 141702.doc -19 201113042 copies. The combination of the first and second components results in a non-cytotoxic composition comprising an effective amount of a whitening tooth dioxide gas. Precursors of C102 include metal chlorites, metal chlorates, acid sources, and, optionally, halogen sources. The particulate precursor can comprise one of these precursors or any combination of such precursors. An exemplary particulate precursor can be an ASEPTROL product, such as ASEPTROL S-Tab2. ASEPTROL S-Tab2 has a chemical composition (%) by weight: NaC102 (7%); NaHS04 (12%); NaDCC (1%); NaCl (40%); MgCl2 (40%). Example 4 of U.S. Patent No. 6,432,322 describes an exemplary manufacturing method of S-Tab2. Subsequent compaction by pulverizing the compressed S-Tab2 tablet or from the uncompressed powder of the S-Tab2 component, followed by decomposing the resulting compacted strip or brick, and obtaining the sieve Need to size, produce particles. Chlorine dioxide is formed from the ASEPTROL particles after exposure to water or an aqueous thickening fluid. In one embodiment, a substantially non-cytotoxic composition comprising chlorine dioxide is prepared by combining about 40 mesh particles with an aqueous thickening fluid. In one aspect, the thickener component of the thickening fluid is carboxymethylcellulose. The aqueous thickening fluid can be prepared sufficiently prior to combination with the ASEPTROL granules to allow the thickener component to be fully hydrated. In one embodiment, the thickened fluid composition is formed by adding a high viscosity NaCMC powder to distilled water. The NaCMC can be allowed to hydrate for at least about 8 hours, and then the mixture can be stirred to homogenize. Substantially non-cytotoxic compositions for tooth polishing can then be prepared by mixing the sieved ASEPTROL particles with a NaCMC thickening fluid composition. The thickened fluid composition can also be formed in situ with saliva as the aqueous medium. In one embodiment, a mixture of 141702.doc -20-201113042 ASEPTROL granules and a thickener component can be molded, for example, by the addition of ductility, and then the enamel shape is applied to the teeth. The saliva activates the granules to form a oxidizing gas and a thickener component hydrate to form a thickened fluid composition in situ. In another example, a mixture of ASEPTROL particles and thickener components can be placed on a dental strip or dental film or placed in a tray. A dental strip refers to a substantially planar rainbow made of a plastic skeleton that is sufficiently flexible to adhere to the teeth. A dental film refers to a substantially planar object made of a commercially available material that can substantially conform to the surface of the tooth. Optionally, the dental strip can be dissolved in an aqueous medium such as saliva. A strip, film or tray is placed over the teeth and the saliva acts as an aqueous medium as described above to produce a thickened fluid composition in situ. Alternatively, the mixture on the strip or tray is contacted with water or an aqueous medium prior to placement on the teeth. There is no extremely accurate method for directly measuring the oxygen-chloride anion in the thickened fluid composition. However, this value can be accurately estimated by measuring the oxygen-chlorine anion in the aqueous solution (before thickening) and adjusting the final concentration based on the weight of the final thickened fluid. It is expected that the titration described elsewhere herein will be useful for assessing both the chlorine dioxide concentration and the oxygen 'chlorine anion concentration' of the thickened fluid composition. It is contemplated that the oxygen-chlorine anion in the thickened fluid composition can be measured using an ion chromatography as described elsewhere herein, with the proviso that steps are taken to prevent the hydrated thickener component from contaminating the column. - This step is to use a molecular weight transitioner to remove the hydration stabilizer component (such as hydrated CMC) prior to application to the chromatography column. If desired, the fluid composition can be diluted with water prior to analysis to reduce its viscosity or otherwise make it easier to test. Those skilled in the art can readily determine whether a given formulation is sufficiently low by using the USP bioreactivity limit of the usp<87>2 loam 141702.doc 201113042 dispersion test to determine if the formulation is cytotoxic. Oxygen-chlorine concentration. The aqueous thickening fluid composition for carrying out the method may comprise any thickening agent component in an aqueous medium, wherein the thickened fluid composition is non-cytotoxic and non-irritating to soft tissues, especially oral mucosa, and Hard tissue, such as enamel and tooth, causes minimal damage. In addition, the thickener is preferably not detrimental to the polishing agent during the time scale of composition preparation and processing. Many thickening agents are known in the art including, but not limited to, carbomers (e.g., CARBOPOL thickener, Lubrizol Corp., Wickliffe, OH), carboxymethyl cellulose (CMC). , ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, natural montmorillonite clay (eg VEEGEM, RT Vanderbilt Co., Norwalk, CT), synthetic clay (eg LAPONITE (Southern Clay Products, Gonzales, TX)), methylcellulose, superabsorbent polymers (such as polyacrylates (eg LUQUASORB 1010, BASF, Florham Park, NJ)), poloxamer (PLURONIC, BASF, Florham Park, NJ), Polyethylene glycol, sodium alginate, xanthine and xanthan gum. These thickeners can be classified into four groups: natural hydrocolloids (also known as "glue"), semi-synthetic hydrocolloids, synthetic hydrocolloids and clays. Some examples of natural hydrocolloids include acacia, tragacanth, alginic acid, carrageenan, locust bean gum, guar gum, and gelatin. Non-limiting examples of semi-synthetic hydrocolloids include mercaptocellulose and sodium carboxymethylcellulose. Synthetic hydrocolloids (also known as "polymers" including polymers, crosslinked polymers and copolymers) 141702.doc -22- 201113042 Some examples include polyacrylates, superabsorbent polymers, high molecular weight polyethylene Alcohol and polypropylene glycol, polyethylene oxide and CARBOPOL. Non-limiting examples of clays (including expanded clay) include LAPONITE, attapulgite, bentonite, and VEEGUM. Exemplary thickener components can be semi-synthetic hydrocolloids. The thickener component can also be a high viscosity sodium carboxymethyl cellulose (NaCMC powder). CMC is a cellulose derivative in which a carboxymethyl group (-CH2-COOH) is bonded to some of the base groups of the grape pentose monomer constituting the cellulose skeleton. It is synthesized by catalytic reaction of cellulose with an alkali metal of chloroacetic acid. The polar (organic acid) carboxyl group makes the cellulose soluble and chemically reactive. The functional properties of CMC depend on the degree of substitution of the cell structure (i.e., the number of hydroxyl groups that have been involved in the substitution reaction) and the chain length of the cellulosic framework structure. A range of CMCs with a viscosity rating and meeting USP standards are available. High viscosity CMC (such as CA194 from Spectrum Chemical Manufacturing Company) has a viscosity of between about 1500 and 3 000 cps at 25 ° C at 1% concentration in water. One composition is in the form of a fluid. In certain embodiments, the fluid can be a thickened fluid having flow properties suitable for applying a fluid to the tooth surface and maintaining the fluid in place during the duration of the tooth polishing process (eg, from about 5 to about 60 minutes). . Thus, a pseudoplastic composition having a yield point sufficient to retain its shape when applied to the teeth but low enough to be easily removed by wiping can be advantageous in practicing the method. In embodiments in which the composition is contacted with a tooth using a tray, strip or similar device, the composition should have sufficient adhesion to hold the device in place. Exemplary adhesives are disclosed in 141, 702. doc -23-201113042, U.S. Patent Publication No. 2008/0025925. The compositions used in the process may optionally contain other components. In certain embodiments, the composition does not include any abrasive components. In other embodiments, the composition may contain a minor effective amount of an abrasive component. In such embodiments the amount of the abrasive component is substantially less than the effective amount. "Substantially less than" means that at least about 25% is less than the effective amount of the abrasive, or at least about 5% is less than the effective amount' or at least about 75% less than the effective amount. Abrasive group injuries known in the art include monoxide eve; borax citrate glass platelets; dish salts, including sulphonate, polymetaphosphate and pyrophosphate; carbonates such as hydrogencarbonate Nano and calcium carbonate (white peony); resin abrasive materials; and alumina. In other embodiments, the composition contains substantially less than an effective amount of the abrasive component used to polish in the absence of chlorine dioxide. That is, it is contemplated that the polishing performance of the specified amount of abrasive can be achieved by a composition comprising chlorine dioxide and less than, and preferably less than, a specified amount of the abrasive component. Although mechanical grinding will occur in such embodiments, it is expected that mechanical milling will be at a substantially reduced level' while still achieving tooth polishing due to a reduction in the amount of mechanical abrasive in the composition. Other optional components which may be present in the composition include, but are not limited to, sweeteners, flavoring agents, coloring agents, and fragrances. Sweeteners include sugar alcohols. Exemplary sugar alcohols include sorbitol, xylitol, lactitol, mannitol, maltitol, hydrogenated starch hydrolysate, erythritol, reducing paratinose, and mixtures thereof. Flavoring agents include, for example, natural or synthetic essential oils as well as various flavoring aldehydes, glycerides, alcohols, and other materials. Examples of essential oils include spearmint oil, peppermint oil, wintergreen oil, 141702.doc •24· 201113042 re-oil, clove oil, sage oil, tree oil, horse simmered oil, cinnamon oil 'lime oil, rai Lime oil, grapefruit oil and orange oil. Colorants include those approved by regulatory agencies for incorporation into foods, pharmaceuticals or cosmetics' such as FD&C or D&C pigments and dyes approved for use in the United States by the FDA. Fragrances include menthol, menthyl acetate, menthyl lactate, eucalyptus, eucalyptus oil, eucalyptol, aniseed brain, eugenol, cinnamon, dioxane, oxanone, alpha-ionone, Propylene-based guaiacol, thymol, linalool, benzaldehyde, cinnamaldehyde, hydrazine-ethyl-p-menthane, small carbamide, hydrazine, 2,3-dimethyl-2-isopropyl Amine, 3-(1-decyloxy)-propanone-1,2-diol, cinnamaldehyde glycerol acetal (CGA), menthone glycerol acetal (MGA) and the like. Other optional components of the composition include: antibacterial agents (other than chlorine dioxide), enzymes, malodor control agents (other than chlorine dioxide), detergents (such as phosphate), anti-gingivitis agents, Antiplaque agents, anticalculus agents, anti-caries agents (such as fluoride ion sources), anti-periodontal agents, nutrients, anti-sputum agents and the like. Exemplary agents are well known in the art. See, for example, U.S. Patent Publication No. 2005/0287084, No. 2-6/〇2633〇6, No. 2007/0259011, and No. 2008/0044363. Preferably, all components selected as appropriate have a relative resistance to oxidation by oxidizing gas, which is attributed to the reduction of chlorine dioxide which can be used to polish the tooth surface by oxidation of the composition component by chlorine dioxide. In the time scale for preparing a composition comprising chlorine dioxide and using a chlorine-containing composition in the process, the function of the component selected as appropriate is not substantially impaired and the composition retains its polishing efficacy. The composition is also 141702.doc -25- 201113042 Qualitatively non-cytotoxic, substantially non-irritating, and does not substantially damage the hard tissues of the teeth. Ι][·Usage Method j The 1 method of operation is to contact the surface of the tooth with the composition. The composition contains an effective amount of a polishing agent which can be thrown into contact with the surface of the tooth without mechanical grinding. The composition can be and should be substantially non-cellular and non-irritating. Contact with the teeth to achieve a measurable period of tooth polishing ^ Continuation _ is readily understood by those skilled in the art in light of the teachings herein. Advantageously, the composition does not substantially damage the hard tissue of the teeth even after prolonged contact. Although the contact may be up to 16, 17, 18, 19 or minutes, or up to a maximum of about 2:, 28, 29 or 30 minutes, or at most about H 45, 50, 55 2: knife or at some In some cases, the longer range of time 'but the duration of contact is generally in the range of seconds to minutes, at least ^ 5, 3 (), 45_ seconds, at least about 1, 2, 1 / 1 bucket, r, spoon 3, 4 or 5 minutes, about 6, 7, 8, 9 or 10 minutes * 12 13, 14 or 15 minutes. In certain embodiments, the contact is in a range between about 丨 and about 6 〇 minutes: to about 3 〇 minutes, and more preferably (four) to (four) minutes. In another implementation: the duration of contact for processing can be about 15 minutes. The frequency of processing is also readily determined by those skilled in the art. This treatment may include one tooth contact process or more than one time. The number of treatments can be continuous, at intervals (e.g., hours to days, days to weeks, and longer intervals including months to years or years) or both. Contact between the composition and the surface of the tooth can be achieved by any of a number of methods known in the art 141702.doc -26 · 201113042. The composition can be brushed or applied to the surface of the tooth. The composition can be sprayed or foamed onto the surface of the tooth. The composition can be present on a flexible strip or patch that can be applied to and molded against the surface of the tooth. The composition can be used as a mouthwash; therefore, the composition can be held in a password and allowed to be static, or accompanied by the use of, for example, a tongue and annoying agitation in the mouth to contact the teeth. The composition can be placed in a tray and the tray can then be placed in contact with the teeth. These trays can be customized or undefined. A number of devices suitable for carrying out such methods are disclosed in this technical order, including but not limited to U.S. Patent Nos. 5,879,691, 6,55 1,579, 6,682,721 5, 6,848,9,5,F, and 6,896,518, 6,964,571, 7th, Q()4,756, 7th, (4), 897, US Boxing, A, 2006/0223033, 2007/0298380, and 2008/00259255, and international patents Publication No. pCT/US2〇〇6/〇6i〇9. The entire text of each of these references is hereby incorporated by reference. In certain embodiments, the method can be performed using a tray. In one aspect, the tray is custom made. A method of making a custom-made tray is well known in the art; for example, see U.S. Patent Nos. 6,1,6,284 and M25,759 and U.S. Patent Publication No. 2/6/183,183. And the second ____. The entire text of each of these references is hereby incorporated by reference in its entirety in its entirety, the <RTIgt;''''' The Yintuo is then placed in the patient's mouthpiece to produce a negative impression of the primary tooth in the (4) material. After the negative impression has been formed, the negative impression produced by the impression tooth is made of a soft cast material (such as dental hard plaster (d 141702.doc -27· 201113042 st〇ne), gypsum or epoxy resin) )filling. The impression tray is then flipped over and mounted on a pre-installed device, such as a dental scale tray or base. After the town & material has a chance to harden, the impression tray is removed to cause the cast material to form a positive dental impression on the mounting surface. Another method of preparing a custom tooth tray is to use a boiling and "female" material, such as ethylene vinyl acetate \ y Vlnyl aeetate 'EVA" or a thermoformed plastic garment of a polystyrene. By heating the thermoformable plastic in the Buddha water, it is biologically acceptable, θ Λ 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰 舰,, ', the cold part of the tooth and maintain its new shape. To achieve this method, a substantially non-cytotoxic composition of & non-abrasive polishing agents is placed in the tray. ψ The tray is then placed in the patient's mouth to handle the event. It is also contemplated that the chlorine dioxide composition can be made by minimizing contact of the soft tissue with the oxygen-chlorine anion present in the composition or by preventing contact of the soft tissue with the milk-chlorine anion present in the composition. The administration is essentially 1 cytotoxic. Therefore, as an example, it is envisaged to include a microporous barrier that allows the oxidized rat to pass through and substantially does not allow the oxygen-chlorine anion to permeate.

裝置。一乳化虱組合物可由該可選擇性透過之障壁完全或 部分地包圍。在草此眚e A 一 m例中,膜為疏水性的;膜之疏水 性貝防止水性反應介質及水 .. J^生接爻介處(recipient medium) 兩者穿過膜。用於該障壁 土之材枓之待考罝之特徵包括:微 孔材料之疏水性、孔种 焊 厚度及對於二氧化氯、氣、亞氯 咬X、氣酸根 '氯離子、酸及驗之侵襲之化學安定性。當 然,對於與軟組織接觸而言, 尤其在裝置之典型使用之時 141702.doc -28- 201113042 間標度下,微孔性障壁應為實質上非刺激性及實質上非細 胞毒性的。設想在該裝置中所利用之二氧化氯組合物不: 為稠化流體,其限制條件為裝置可附著於牙齒表面,且使 得透過膜之二氧化氯能夠接觸牙齒表面。 適用作該等障壁之材料在此項技術中為已知的且包括膨 脹聚四氟乙烯(例如G0RE_TEX)及聚偏二氟乙烯(pvdf)。 例如參見美轉㈣4,683,G39號。形成膨脹聚四氟乙缔之 程序描述於美國專利第3,953,566號卜材料可以與提供使 用所需之結構強度之支撐材料所形成的複合物形式提供。 障壁中之札徑可視二氧化氯穿過障壁之所需流動速率而 有很大變化。孔不應太小以致阻止二氧化氯氣體流通,但 亦不應太大以致容許液體流過。 障·^之孔隙率亦可視二氧化氯穿過障壁之所需流動速率 而有很大變化。障壁強度之考慮因素亦規定所選孔隙率。 一般而言,障壁孔隙率自約50%至約98%而不同。 亦預期使用可形成Cl〇2之反應物,囊封於聚合材料妒, 該聚合材料可讓C102透過但實質上不讓氧-氯陰離子透 過。例如參見美國專利第7,273,567號。 如本文中所示,包含二氧化氯作為拋光劑之實質上非細 胞毒性組合物出乎意料地在不存在機械研磨劑的情況下降 低琺瑯質之平均表面粗糙度。相對於接觸之前之琺瑯質表 面粗糙度,琺瑯質表面粗糙度可降低至少約5%,至少約 8%,或至少約12%。齒質之平均表面粗糙度不以統計上顯 著量增加。 14I702.doc -29- 201113042 此外’包含二氧化氯之實質上非細胞毒性組合物對硬表 面(諸如琺螂質及齒質)造成最低程度之損傷,甚至在牙齒 上/、有效里長期接觸期間亦如此。在某些實施例中, 相對於接觸之前之5法瑯質,與實質上非細胞毒性組合物接 觸之玻鄉質之顯微硬度降低程度小於約15%,小於約 10%,小於約8%,或小於約5%。在某些實施例中,相對 :接觸之如之珠螂質,在約7小時之總處理時間之後,綠 螂質顯微硬度降低程度小於約1%。在某些實施例中,相 2於接觸之前之齒質,與實質上非細胞毒性組合物接觸之 齒質之顯微硬度降低程度小於約15%,或小於約10%,或 小於約8〇/〇。S某些實施例中,相對於接觸之前之齒質, 在力7小時之總處理時間之後,齒質顯微硬度降低程度小 於約8%。 因此,如本文中所示,實質上非細胞毒性之包含二氧化 氯之、,且s物已有利地在不存在機械研磨劑的情況下且在不 會實質性刺激e腔黏膜軟組織且不引起牙齒敏感性的情況 下提供牙齒拋光。因此,組合物與口腔軟組織可之實質性 接觸而不引起刺激或細胞毒性。如本文辛所用之「與口腔 軟組織之實質性接觸」係指多於與鄰近所處理牙齒之齒齦 組織之接觸的接觸。因此,實質性接觸包括(但不限於)與 齒酿、頰黏膜及舌組織之接觸。另外,使用實質上非細胞 毒性及非刺激性的包含二氧化氯之組合物對於琺瑯質及齒 質顯微硬度具有最低程度之反作用。高效牙齒拋光伴隨最 思、的’且在先前技術 低程度之不良副作用之此組合為極合 141702.doc -30· 201113042 嘗試中未達成。 二氧化氯隨時間過去而緩慢衰減。因此,當以包含二氧 化氯之組合物實施該方法時,為最大化組合物之牙齒拋光 效能且確保非細胞毒性,如本文中其它地方所描述可在使 用之前即刻製備組合物或可原位製備組合物。可由名為 「N〇n-Cytotoxic Chlorine Di〇xide戶⑹心」之共同讓渡之 美國臨時專利申請案第61/15〇,685號中描述之方法來製 備。 " 在一實施例中,二氧化氯之微粒前驅體可存在於第一施 配器(諸如注射器)中,且水性介質中之稠化劑組份存在於 第二施配器t。可將第二施配器中之水性稠化流體直接添 加至第一細配态中之微粒混合物,使組合反應產生, 且後混合直至均句。或者,可將水性介f添加至微粒前 驅體以製備實質性純二氧化氯溶液。合適量之此溶液可隨 後與另一施配器中之水性稠化劑混合。此等實施例皆宜使 用注射器作為施配器來實施。在任__實施例中,可將兩個 主射窃彼此連接,且藉由將一個注射器之内容物施配至另 一者中來組合内容物,隨後將混合物施配回至另一注射器 中直至/心合物均勻。在另一實施例中,兩個施配器為雙筒 注射器之兩個筒管。製備及施配組合物之其他裝置描述於 名為 N〇n-Cytotoxic Chlorine Dioxide Fluids」之共同讓 渡之美國臨時專利申請案第61/150,685號中。 ΙΠ.套組及其他製品 本發明另外提供一種套組,其包含本發明之組合物,或 141702.doc •31 - 201113042 其成份,及描述在拋光牙齒表面之方法中使用該組合物之 教材。如本文中所使用,「教材」包括出版物、記錄、圖 或任何其他表達媒介,其可用於傳達套組中之本發明之組 合物及/或化合物在無需機械研磨劑而拋光牙齒之方法中 的適用.性。套組之教材可(例如)附著於含有本發明之化合 物及/或組合物之容器或與含有化合物及/或組合物之容2 -起運送。或者’教材可與容器分開運送,目的在於接收 者以協作方式使用教材及化合物。遞送教材可(例如)藉由 傳達套組^適用性之出版物或其他表達媒介之實物遞送達 成,或可藉由電子傳輸達成,例如藉助於電腦,諸如藉由 電子郵件,或自網站下載。 在-實施例中’套組可包含適用於製備組合物之兩個施 配器。-個施配器包含二氧化氯之微粒前驅體。第二施配 器包含水性介質中之稠化劑組份。 在:一實施例中’套組包含兩隔室式容器。一個隔室包 含二氧化氣之微粒前驅體。第二隔室包含水性介質中之稠 化劑組份。容器視情況包含用於組合兩個其他隔室之某些 或全部内容物之第三隔室。 在套組之某些實施例中,微粒前驅體為ASEPTROL顆 粒’諸如ASEPTR0L S_Tab2難。在套,组之某此實施例 中,稠化齡份為⑽。在套組之―態樣中,微粒前驅體 包含ASEPTROL S-Tab2顆粒且稠化劑組份包含⑽匚。 套組另外視情況包含施料器。術語「施料器」如該術語 在本文中所使用⑤w適合於使牙齒表面與組合物接觸之 141702.doc •32· 201113042 任何裝置,包括(但不限於)牙托、注射器、吸管、刷子 杯子及其類似物。 實例 參考以下實驗實例來進—步詳細描述組合物、套組及其 使用方法。此等實例僅出於說明之目的而提供,且除非另 有指示,否則不意欲具有限制性。因此,組合物、套組及其 使用方法無論如何不應視為限於以下實例,而實際上應視為 包涵由於本文中提供之教示而變得明顯之任何及所有變化。 實驗實例1:細胞毒性分析 為測試二氡化氯對於哺乳動物細胞之效應,執行以下實 驗。製備包含不同量之亞氯酸根陰離子之兩個系列之試 樣。實例1 -4使用超級吸附聚丙烯酸酯凝膠(標為凝膠型 「S」)。實例5-8使用羧曱基纖維素(CMC)凝膠(標為凝膠 型「C」)。 " 在用於此實驗中之凝膠組合物中,使用ASEPTROL S-Tab2顆粒。顆粒之化學組成展示於表1中。 組份 表1 酸鈉 氰尿酸鈉鹽 % (wt/wt) 7%Device. An emulsified enamel composition can be completely or partially surrounded by the selectively permeable barrier. In the case of grass 眚 e A , the membrane is hydrophobic; the hydrophobic shell of the membrane prevents the aqueous reaction medium and water. J. The recipient medium passes through the membrane. The characteristics of the material used for the barrier soil include: the hydrophobicity of the microporous material, the thickness of the pore seeding, and the attack on chlorine dioxide, gas, chlorite bite X, chlorate 'chloride ion, acid and test. Chemical stability. Of course, the microporous barrier should be substantially non-irritating and substantially non-cytotoxic for contact with soft tissue, especially at the time of typical use of the device 141702.doc -28- 201113042. It is envisaged that the chlorine dioxide composition utilized in the apparatus does not: is a thickened fluid, the restriction being that the device can adhere to the tooth surface and the chlorine dioxide permeable to the membrane can contact the tooth surface. Materials suitable for use as such barriers are known in the art and include expanded polytetrafluoroethylene (e.g., G0RE_TEX) and polyvinylidene fluoride (pvdf). See, for example, Mito (4) 4,683, G39. The procedure for forming expanded polytetrafluoroethylene is described in U.S. Patent No. 3,953,566. The material can be provided in the form of a composite formed by a support material that provides the structural strength required for use. The diameter of the barrier can vary greatly depending on the desired flow rate of chlorine dioxide through the barrier. The holes should not be too small to prevent the flow of chlorine dioxide gas, but should not be too large to allow liquid to flow through. The porosity of the barrier can also vary greatly depending on the desired flow rate of chlorine dioxide through the barrier. The barrier strength considerations also dictate the porosity chosen. In general, the barrier porosity varies from about 50% to about 98%. It is also contemplated to use a reactant which forms Cl?2, encapsulated in a polymeric material which allows C102 to pass through but does not substantially allow the oxygen-chlorine anion to pass through. See, for example, U.S. Patent No. 7,273,567. As shown herein, substantially non-cytotoxic compositions comprising chlorine dioxide as a polishing agent unexpectedly reduce the average surface roughness of the low tannin in the absence of mechanical abrasives. The enamel surface roughness can be reduced by at least about 5%, at least about 8%, or at least about 12% relative to the enamel surface roughness prior to contact. The average surface roughness of the tooth quality does not increase by a statistically significant amount. 14I702.doc -29- 201113042 Furthermore 'substantially non-cytotoxic compositions containing chlorine dioxide cause minimal damage to hard surfaces such as tannins and dentin, even during long-term exposure on teeth/effectively The same is true. In certain embodiments, the microhardness of the glassy soil contacted with the substantially non-cytotoxic composition is less than about 15%, less than about 10%, less than about 8% relative to the 5 enamel prior to contact. , or less than about 5%. In certain embodiments, the green enamel microhardness is reduced by less than about 1% relative to the contacted bead enamel after a total processing time of about 7 hours. In certain embodiments, the phase 2 is prior to contact with the dentin, and the microhardness of the dentin in contact with the substantially non-cytotoxic composition is less than about 15%, or less than about 10%, or less than about 8 Å. /〇. In some embodiments, the dentin microhardness reduction is less than about 8% after a total treatment time of 7 hours relative to the densities prior to contact. Thus, as shown herein, substantially non-cytotoxic includes chlorine dioxide, and the s has advantageously been in the absence of mechanical abrasives and does not substantially stimulate the soft tissue of the ecavity mucosa and does not cause Dental polishing is provided in the case of tooth sensitivity. Thus, the composition can be in substantial contact with the oral soft tissue without causing irritation or cytotoxicity. As used herein, "substantial contact with oral soft tissue" refers to contact with more contact with the gingival tissue of a nearby treated tooth. Thus, substantial contact includes, but is not limited to, contact with the teeth, buccal mucosa, and tongue tissue. In addition, the use of substantially non-cytotoxic and non-irritating compositions comprising chlorine dioxide has minimal adverse effects on tannin and dentin microhardness. Efficient tooth polishing is accompanied by the most inconspicuous and the combination of adverse side effects in the prior art is extremely high. 141702.doc -30· 201113042 The attempt was not reached. Chlorine dioxide slowly decays over time. Thus, when the method is practiced in a composition comprising chlorine dioxide, to maximize tooth polishing performance of the composition and to ensure non-cytotoxicity, the composition can be prepared immediately prior to use as described elsewhere herein. A composition is prepared. It can be prepared by the method described in U.S. Provisional Patent Application Serial No. 61/15, No. 685, entitled "N.N.-Cytotoxic Chlorine Di. " In an embodiment, the particulate precursor of chlorine dioxide may be present in a first dispenser, such as a syringe, and the thickener component in the aqueous medium is present in the second dispenser t. The aqueous thickening fluid in the second dispenser can be added directly to the particulate mixture in the first fine mode, resulting in a combined reaction, and then mixed until the same sentence. Alternatively, aqueous medium f can be added to the particulate precursor to prepare a substantially pure chlorine dioxide solution. A suitable amount of this solution can then be mixed with the aqueous thickener in another dispenser. These embodiments are all preferably implemented using a syringe as a dispenser. In any embodiment, the two main thefts can be connected to each other, and the contents are combined by dispensing the contents of one syringe into the other, and then the mixture is dispensed back into another syringe until / The heart is homogeneous. In another embodiment, the two dispensers are two bobbins of a dual barrel syringe. Other devices for the preparation and application of the compositions are described in U.S. Provisional Patent Application Serial No. 61/150,685, the entire disclosure of which is incorporated herein by reference.套. Kits and Other Articles The present invention further provides a kit comprising the composition of the present invention, or the composition of 141702.doc • 31 - 201113042, and a textbook describing the use of the composition in a method of polishing a tooth surface. As used herein, "textbook" includes publications, records, figures, or any other expression medium that can be used to convey a composition and/or compound of the invention in a kit in a method of polishing teeth without the need for mechanical abrasives. Applicability. Sex. The kit may be, for example, attached to a container containing the compound and/or composition of the present invention or shipped in a container containing the compound and/or composition. Alternatively, the textbook can be shipped separately from the container for the recipient to use the textbook and compounds in a collaborative manner. The delivery of the teaching material can be achieved, for example, by physical delivery of a publication or other expression medium that conveys the suitability of the kit, or can be achieved by electronic transmission, such as by means of a computer, such as by e-mail, or downloaded from a website. In an embodiment, the kit can comprise two dispensers suitable for use in preparing the composition. - The dispenser contains a particulate precursor of chlorine dioxide. The second dispenser comprises a thickener component in an aqueous medium. In one embodiment, the kit comprises a two compartment container. One compartment contains a particulate precursor of oxidizing gas. The second compartment contains a thickener component in an aqueous medium. The container optionally includes a third compartment for combining some or all of the contents of the two other compartments. In certain embodiments of the kit, the particulate precursor is ASEPTROL granules such as ASEPTROL S_Tab2. In one embodiment of the set, the thickened age is (10). In the case of the kit, the particulate precursor comprises ASEPTROL S-Tab2 particles and the thickener component comprises (10) ruthenium. The kit also includes an applicator as appropriate. The term "applicator" as used herein by the term 5w is adapted to contact the surface of the tooth with the composition. 141702.doc • 32· 201113042 Any device including, but not limited to, trays, syringes, straws, brush cups And its analogues. EXAMPLES Referring to the following experimental examples, the compositions, kits, and methods of use thereof are described in detail. These examples are provided for illustrative purposes only and are not intended to be limiting unless otherwise indicated. Therefore, the compositions, kits, and methods of use thereof are not to be considered as limited to the following examples, but are to be construed as covering any and all variations that are apparent from the teachings provided herein. Experimental Example 1: Cytotoxicity assay To test the effect of dichlorosilane on mammalian cells, the following experiment was performed. Two series of samples containing different amounts of chlorite anions were prepared. Example 1-4 used a superabsorbent polyacrylate gel (labeled as gel type "S"). Examples 5-8 used a carboxymethyl cellulose (CMC) gel (labeled as gel type "C"). " In the gel composition used in this experiment, ASEPTROL S-Tab2 particles were used. The chemical composition of the particles is shown in Table 1. Component Table 1 Sodium Cyanide sodium salt % (wt/wt) 7%

亞氯酸鈉(Aragonesas Energia,Spain)為工業級的,含 有標稱80重量% (0.8) NaC1〇2及20%無機安定劑鹽,諸如 141702.doc -33- 201113042Sodium chlorite (Aragonesas Energia, Spain) is industrial grade containing nominally 80% by weight (0.8) NaC1〇2 and 20% inorganic stabilizer salts, such as 141702.doc -33- 201113042

NaCl、NaOH、Na2C03 及 Na2S〇4。自 Oxychem 獲得稱為 ACL-56 之二氣異氰尿酸鈉鹽(NaCl2(CN0)3.2H20)。 錠劑(可自其製得顆粒)基本上如美國專利第6,432,322號 之實例4中所描述而製備,該參考案以引用的方式併入本 文中。簡言之,將顆粒之每一獨立組份乾燥。將合適數量 之組份一起混合且使用液壓台式壓力機將混合物壓實為錠 劑形式。使用研蛛及研杵將由此形成之鍵劑研磨成顆粒。 使用40篩目美國標準篩來篩分所得顆粒;將-40篩目大小 部分用於實驗中。 ASEPTROL S-Tab2錠劑具有亞氯酸根陰離子轉化為C102 之較高轉化度(參見美國專利第6,432,322號中之實例)。通 常,由該等錠劑製得之溶液含有如殘餘亞氯酸根陰離子約 10倍之多的C102。當與水(液體)接觸時,水被吸收至錠劑 之孔中,其在該等孔中形成組份之飽和水溶液。該等條件 (高濃度之亞氣酸根陰離子及低pH值)宜於藉由以下反應使 亞氣酸根陰離子(C10〇與酸或氯反應來產生二氧化氯 (Cl〇2): 5NaC102+4H+-> 4C102+NaCl+4Na++2H2O 方程式 3 2NaC102+0Cr+H+-> 2C102+NaCl+Na0H 方程式 4 溶解狀態下之殘餘亞氯酸根陰離子可由若干來源產生。 溶解狀態下之殘餘亞氣酸根陰離子之一個來源為亞氯酸 鈉,其自ASEPTROL錠劑(或顆粒)之外表面溶解至本體溶 液中。在本體溶液之極稀及一般中性pH值條件下,亞氯酸 I41702.doc -34- 201113042 根陰離子轉化為⑽之轉化率較低,因此自錠劑或顆粒外 部溶解之任何亞氯酸根陰離子保持實質上未轉化且保持呈 溶解狀態下之亞氯酸根陰離子形式。結果,在亞氯酸納轉 化為⑽2之前增強亞氯酸納之表面溶解之任何事物均將引 起所得溶液或凝膠中之亞氯酸根陰離子濃度增加。 每一基質凝膠(水性稠化流體)對於補償最終試樣中之不 , @活性成份濃度猶有不同。所製備凝膠試樣中之稠化剤組 份之最終濃度在每一系列内為相同的。每一試樣以約川公 克之量製得。藉由將去離子水與膠凝劑(稍化劑組份)組合 來製備基質凝膠。為使膠凝劑變得完全水合,使混合物靜 置數小時至隔夜。隨後攪拌基質凝膠混合物以使基質疑膠 均質化。 藉由在使用之前不久將ASEPTR〇L顆粒與基質凝膠組合 來製備試樣。在使用之前將ASEPTR〇L材料對於環境濕度 或水之曝露降至最低程度以避免效能損失。將ASEpTR〇L 顆粒添加至基質凝膠之後,以不鏽鋼或塑膠抹刀將試樣混 合30秒,加蓋且在室溫下保持靜置5分鐘。隨後第二次將 試樣混合30秒以使試樣均質化。將所製備之試樣緊密地加 蓋直至測s式時間。保護亞氣酸鈉顆粒及所製備之試樣不受 強紫外光照射以限制紫外光誘導之分解。製備試樣之後不 超過2小時開始測試。 使用蛾化鉀(KI)且對於其他試樣使用硫代硫酸鈉,藉由 PH 7緩衝滴定法來評定二氧化氯濃度。試樣丨及5具有零二 氧化氣。試樣2及6具有約3 0 ppm C102。試樣3及7具有約 141702.doc •35- 201113042 40 ppm且試樣4及8具有約580 ppm Cl〇2。 不存在直接量測稠化流體組合物中之亞氯酸根陰離子之 極精確方法。因此,以下提供可能存在於每一所製備試樣 中之亞氣酸根陰離子之最大濃度。因為反應物在水性介質 之存在下活化且生成二氧化氯,由此消耗亞氯酸根陰離 子,所以預期亞氣酸根陰離子之實際量小於最大量。使用 下式計算可能存在於試樣中之亞氣酸根陰離子之最大量: ((S_tab2顆粒之重量X顆粒中之亞氣酸鈉之重量分率X亞氯 酸鈉中之亞氯酸根重量分率X亞氯酸鈉之標稱重量分率)x 1000)/最終試樣之總重量。用於S-Tab2顆粒中之亞氯酸鈉 之重量分率為0.07。亞氯酸鈉中之亞氣酸根之重量分率為 0.74。用於顆粒中之亞氯酸鈉粉末中之實際亞氯酸鈉的標 稱重量分率(亦即亞氯酸鈉之純度)為0.8。因此,例如對於 實例2而言,每公克凝膠之氧-氯陰離子之毫克數經計算 為: ((0.143 gxO.07x0.74x0.8)xl000)/30公克最終試樣。 實例之最終調配物展示於表2及3中。 表2 組份 試樣1 試樣2 試樣3 試樣4 聚丙烯酸鈉1 1.4 1.4 1.4 1.4 NaCl 1 1 1 0 聚氧化乙烯2 1.6 1.6 1.6 1.6 去離子水 26 25.9 25.6 25.6 S-Tab2顆粒(-40篩目) 0 0.143 0.357 1.43 每公克凝膠之亞氯酸鎂最大值 0 0.2 0.5 2.0 1- LUQUASORB 1010, BASF Corp 2- POLYOX WSR N3000, Dow Chemical Corp。 141702.doc -36- 201113042NaCl, NaOH, Na2C03 and Na2S〇4. A sodium diisocyanurate salt (NaCl2(CN0)3.2H20) called ACL-56 was obtained from Oxychem. Lozenges, from which granules can be made, are prepared substantially as described in Example 4 of U.S. Patent No. 6,432,322, the disclosure of which is incorporated herein by reference. Briefly, each individual component of the granules is dried. The appropriate number of ingredients were mixed together and the mixture was compacted into a tablet form using a hydraulic bench press. The bond thus formed was ground into granules using a research spider and a mortar. The resulting granules were sieved using a 40 mesh U.S. standard sieve; the -40 mesh size fraction was used in the experiment. ASEPTROL S-Tab2 tablets have a higher degree of conversion of chlorite anions to C102 (see examples in U.S. Patent No. 6,432,322). Typically, the solution prepared from the tablets contains about 10 times as much C102 as the residual chlorite anion. When contacted with water (liquid), water is absorbed into the pores of the tablet, which forms a saturated aqueous solution of the components in the pores. These conditions (high concentration of sulphonate anion and low pH) are suitable for the production of chlorine dioxide (Cl〇2) by reacting a sulphonate anion (C10 oxime with acid or chlorine) by the following reaction: 5NaC102+4H+- > 4C102+NaCl+4Na++2H2O Equation 3 2NaC102+0Cr+H+-> 2C102+NaCl+Na0H Equation 4 Residual chlorite anion in dissolved state can be produced from several sources. Residual sulphonate anion in dissolved state One source is sodium chlorite, which dissolves from the surface of the ASEPTROL tablet (or granule) into the bulk solution. Under the extremely dilute and generally neutral pH conditions of the bulk solution, chlorous acid I41702.doc -34 - 201113042 The conversion of the root anion to (10) is low, so any chlorite anion dissolved from the outside of the tablet or granule remains substantially unconverted and remains in the form of a chlorite anion in a dissolved state. Anything that enhances the surface dissolution of sodium chlorite before the conversion of sodium to (10) 2 will cause an increase in the concentration of chlorite anion in the resulting solution or gel. Each matrix gel (aqueous thickening fluid) pair To compensate for the difference in the final sample, @active ingredient concentration is different. The final concentration of the thickened bismuth component in the prepared gel sample is the same in each series. The matrix gel was prepared by combining deionized water with a gelling agent (dimudge component). To allow the gelling agent to become fully hydrated, the mixture was allowed to stand for several hours to overnight. Gel mixture to homogenize the base challenge gel. Prepare the sample by combining the ASEPTR 〇L granules with the matrix gel shortly before use. Minimize the exposure of the ASEPTR 〇L material to ambient humidity or water prior to use. To avoid loss of performance. After adding ASEpTR〇L particles to the matrix gel, mix the samples with stainless steel or plastic spatula for 30 seconds, cap and keep at room temperature for 5 minutes. Then test for the second time. The sample was mixed for 30 seconds to homogenize the sample. The prepared sample was tightly capped until the s time was measured. The sodium sulfite particles and the prepared sample were protected from strong ultraviolet light to limit ultraviolet light induction. Decomposition The test was started no more than 2 hours after the sample. The concentration of chlorine dioxide was evaluated by pH 7 buffer titration using potassium molybdate (KI) and sodium thiosulfate for other samples. Samples 5 and 5 have zero oxidization. Samples 2 and 6 have approximately 30 ppm C102. Samples 3 and 7 have approximately 141702.doc • 35-201113042 40 ppm and Samples 4 and 8 have approximately 580 ppm Cl〇2. An extremely precise method of chlorite anion in a fluid composition. Thus, the maximum concentration of nitrousate anion that may be present in each prepared sample is provided below. Since the reactant is activated in the presence of an aqueous medium and produces chlorine dioxide, thereby consuming a chlorite anion, the actual amount of the sulphonate anion is expected to be less than the maximum amount. Calculate the maximum amount of nitrous acid anion that may be present in the sample using the following formula: ((S_tab2 weight of the particles X weight fraction of sodium sulfite in the particles X chlorite weight fraction in sodium chlorite) The nominal weight fraction of X sodium chlorite) x 1000) / total weight of the final sample. The weight fraction of sodium chlorite used in the S-Tab2 particles was 0.07. The weight fraction of the sub-alcoholate in sodium chlorite was 0.74. The nominal weight fraction (i.e., the purity of sodium chlorite) of the actual sodium chlorite used in the sodium chlorite powder in the granules is 0.8. Thus, for example, for Example 2, the number of milligrams of oxygen-chlorine anion per gram of gel is calculated as: ((0.143 gxO.07x0.74x0.8)xl000) / 30 grams of final sample. The final formulations of the examples are shown in Tables 2 and 3. Table 2 Component Sample 1 Sample 2 Sample 3 Sample 4 Sodium Polyacrylate 1 1.4 1.4 1.4 1.4 NaCl 1 1 1 0 Polyethylene oxide 2 1.6 1.6 1.6 1.6 Deionized water 26 25.9 25.6 25.6 S-Tab2 granules (- 40 mesh) 0 0.143 0.357 1.43 Magnesium chlorite per gram of gel Max 0 0.2 0.5 2.0 1- LUQUASORB 1010, BASF Corp 2- POLYOX WSR N3000, Dow Chemical Corp. 141702.doc -36- 201113042

根據USP<87>來測試每一所製備之試樣。該方法包括使 用瓊脂擴散測試來測定哺乳動物細胞培養物與局部凝谬產 物接觸之後的生物反應性。此測財之細胞為在補充有血 清之MEM(最低必需培養基)中培養之[929鳴乳動物㈠、鼠) 纖維母細胞》將大於80%匯合度之細胞單層在”它下、在 濕润恆溫箱令生長至少24小時’且隨後以瓊脂覆蓋。遭脂 層充當保護細胞使之免於機械損傷之「緩衝物」,同時容 許可浸出之化學品自測試樣本擴散。將待測試之材料施加 於一張濾紙,隨後將其置放於瓊脂上。 特定言之,將紙錠(paper disk)浸泡於無菌鹽水中以使紙 錠飽和。測定所吸收之鹽水量(潤濕前後將紙錠稱重)。將 一些測試樣本施配於调濕紙錠之表面上。將樣本等分誠樣 保持於紙錠之邊界内但不散布於整個紙錠上。再次將具有 樣本等分試樣之紙錠稱重以評定紙錠上之試樣之量。隨後 將紙旋置放於緩脂覆層頂部上。隨時間定期評估培養物之 細胞毒性之跡象且依據如概述於表4中之〇(無細胞毒性之 症狀)至4(重度細胞毒性)的量表來評級。若測試48彳、時 後,曝露於試樣之細胞培養物中無一者展示大於輕度細胞Each of the prepared samples was tested according to USP <87>. The method involves the use of an agar diffusion test to determine the bioreactivity of a mammalian cell culture after contact with a localized clotting product. The cell for this test is a [929 beetle animal (1), mouse) fibroblast cultured in serum supplemented with MEM (Minimum Essential Medium). A cell monolayer with a confluence of more than 80% is under it, in the wet The incubator is allowed to grow for at least 24 hours' and is then covered with agar. The lipid layer acts as a "buffer" that protects the cells from mechanical damage while allowing the leachable chemicals to diffuse from the test sample. Apply the material to be tested to a piece of filter paper and place it on agar. Specifically, a paper disk is immersed in sterile saline to saturate the paper. The amount of brine absorbed was determined (weigh the paper ingots before and after wetting). Some test samples were applied to the surface of the conditioning paper. Keep the sample aliquoted within the boundaries of the paper spindle but not on the entire paper spindle. The paper ingot with the sample aliquot was again weighed to assess the amount of sample on the ingot. The paper is then placed on top of the slow-fat coating. The signs of cytotoxicity of the cultures were periodically assessed over time and were ranked according to a scale as outlined in Table 4 (symptoms of no cytotoxicity) to 4 (severe cytotoxicity). If tested for 48 彳, afterwards, none of the cell cultures exposed to the sample exhibited greater than mild cells.

LSI 141702.doc •37· 201113042 毒性(2級),則試樣視為滿足測試之要求。在48小時期間展 示3或4級反應性之試樣視為具有細胞毒性。 表4 等級 反應性 反應性區域之描述 0 無 樣本周圍或下方無可偵測區域 1 輕微 樣本下方某些畸形或退化之細胞. 2 輕度 限於樣本下方面積之區域 3 中度 區域延伸至超過樣本0.5至1.0 cm 4 重度 區域延伸超過樣本1.0 cm以上 在此實驗實例中,每一所製備實例之測試體積為約0.1 cc。結果展示於表5中。 表5 試樣編號 凝膠類型 每公克凝膠之亞氣酸鎂最大值 測試結果 1 S 0 合格 2 0.2 合格 3 0.5 不合格 4 2.0 不合格 5 C 0 合格 6 0.2 合格 7 0.5 不合格 8 2.0 不合格 陽性對照 不合格 陰性對照 合格 試樣1、2、5及6滿足USP活體外生物反應性之標準,指 示生物相容性。試樣3、4、7及8不滿足USP活體外生物測 試之要求。因此,在此實驗中,亞氯酸根陰離子之最大濃 度大於約0.2 mg亞氣酸根陰離子/公克凝膠之凝膠產生細胞 毒性效應。此等數據表明細胞毒性以劑量依賴性方式與二 氧化氣、氧-氣陰離子或S-TAB2顆粒中之某些其他組份之 存在相關。 141702.doc -38- 201113042 實驗實例2 :細胞毒性分析 為證實細胞毒性由氧-氯陰離子而非其他可能有毒成份 所誘導,執行以下實驗。 製備一系列試樣以測試各種成份或條件在誘導細胞毒性 中之作用。ASEPTROL S-TablO錠劑用以製備此實驗中之 某些試樣。錠劑之化學組成展示於表6中。ASEPTROL S-TablO錠劑基本上如美國專利第6,432,322號之實例5中所描 述而製備。 表6 組份 % (wt/wt) 亞氯酸鈉 26% 二氯異氰尿酸鈉鹽 7% 硫酸氫鈉 26% 氯化鈉 20% 氯化鎂 21% 所有試樣均包含NaCMC作為稠化劑組份。試樣9、16及 17係使用自ASEPTROL S-Tab 10錠劑製備之-40篩目部分顆 粒製備。試樣10、19及20係使用呈非粒化形式之 ASEPTROL S-TablO錠劑之成份製備。特定言之,將五種 成份乾,燥及混合以形成具有展示於表5中之組成的粉末; 粉末未經壓實及粒化。因此,試樣9及10具有相同化學組 成但以呈不同實體形式之固體組份製成。類似地,如同試 樣17及20,試樣16及19具有相同組成,且試樣17及20具有 相同化學組成。試樣11-14係使用具有ASEPTROL錠劑中之 成份之子集的粉末製備,其中一或多種成份經置換(細節 參見表7之第二行)。試樣15含有實質性純C102。試樣18僅 141702.doc -39· 201113042 含有NaCMC。 試樣9-14及16-20如實驗實例丨中描述來製備。簡言之, 藉由在使用之前不久將固體部分(例如ASEpTR〇L顆粒)與 基質凝膠組合來製備試樣。基質凝膠為容許水合之 NaCMC。將固體部分添加至基質凝膠之後,以不鏽鋼或塑 膠抹刀將試樣混合30秒,加蓋且在室溫下保持靜置5分 鐘。隨後第二次將試樣混合3〇秒以使試樣均質化。將所製 備之試樣緊密地加蓋直至測試時間^保護亞氣酸鈉顆粒及 包含亞氣酸鈉之其他固體混合物,及所製備之試樣不受強 紫外光照射以限制紫外光誘導之分解。製備試樣之後不超 過2小時開始測試。 使用水合NaCMC之基質凝膠及實質性純二氧化氯溶液來 製備試樣15,該二氧化氯溶液在製備該試樣之同一天製 備,且開始測試。藉甴將〇.75公克羧甲基纖維素納粉末 (Sigma-Aldrich,700,00〇莫耳重量(典型))添加至19 2公克去 離子水,使混合物在有蓋罐中靜置隔夜,且混合以使基質 ’邊膠均質化來製備基質凝膠。實質性純二氧化氯溶液如下 製備:將I2個ASEPTROL S-TablO鍵劑(各I.5公克)置放於1 公升飲用自來水中,產生>1000 ppm二氧化氯之深黃色源 >谷液。將空氣以約1公升/分鐘之速率鼓泡通入源溶液底部 以自源溶液將二氧化氯汽提至空氣中。隨後將所得充滿二 氧化氣之空氣鼓泡通入1公升去離子水底部以形成純二氧 化氣之溶液。僅Cl〇2及可能某些水蒸氣自源溶液轉移至產 物溶液。所有鹽成份仍保留於源溶液中。結果,產物溶液 141702.doc •40- 201113042 為C102之實質性純溶液。當源溶液之黃色幾乎消失時,結 束鼓泡。使用Hach 2010型UV/可見光分光光度計分析實質 性純二氧化氯溶液試樣之二氧化氯濃度;發現實質性純溶 液含有以重量計700 ppm二氧化氯。將10公克700 ppm純二 氧化氣溶液添加至基質凝膠且混合以產生含有約233 ppm 二氧化氯且實質上無氧-氯陰離子的凝膠。如同上述,保 護含有NaC102之組份及所製備試樣不受強光照射以限制紫 外光誘導之分解。亦保護所有無水固體成份以免曝露於水 (例如環境濕度)。 除試樣1 7及20以0.04 cc劑量,而非0.1 cc劑量測試之 外,如實驗實例1中所描述測試試樣。製備試樣之後不超 過2小時開始測試。 結果展示於表7中。 表7 試樣 編號 每公克最終凝膠之 亞氯酸錯最大值 USP<87>之結果 9 以ASEPTROL S-TablO顆粒製備 0.5 不合格 10 以ASEPTROL S-TablO之非粒化 成份製備 0.5 不合格 11 NaDCCA經三聚氰酸置換 0.5 不合格 12 NaC102 經 NaCl 置換 0 合格 13 移除NaDCCA 0.5 不合格 14 NaC102經NaCl置換,且 NaDCCA經三聚氰酸置換 0 合格 15 以純C102(無其他鹽)製備 0.5 合格 16 以3倍水製備之試樣9 0.17 不合格 17 試樣9,紙錠上之0.04 cc劑量 0.5 不合格 18 無顆粒、鹽或C102之單獨 NaCMC 0 合格 19 以3倍水製備之試樣10 0.17 不合格 20 試樣10,紙鍵上之0.04 cc劑量 0.5 不合格 陽性對照 0 不合格 陰性對照 0 合格 141702.doc -41 - 201113042 試樣9-11、13、16、17、19及20全部未能滿足usp活體 外生物反應性之彳示準。因此’模擬U S P < 8 7 >之溶離型測試 並未改變結果(比較試樣1〇與19,及試樣9與16) 降低劑量 並未改變結果(比較試樣9與17,及試樣1〇與20)。此等數據 指示用於測試中之劑量或使用具有3倍水之凝膠皆未在所 觀察到之細胞毒性中起作用。 5式樣9及10之結果指示ASEPTROL組份之實體形式不顯 著地影響細胞毒性。試樣i i及13之結果指示產氣劑 NaDCC A之存在不顯著地影響細胞毒性。此結果至少表明 所觀察到之細胞毒性並非由氣產生。 試樣12、14、15及18滿足USP活體外生物反應性之標 準,指示生物相容性。此等數據指示細胞毒性並非由單獨 膠凝劑(試樣1 8)所引起。含有純ci〇2且不含其他鹽之試樣 1 5未導致細胞病變效應的觀察結果指示二氧化氣本身並非 在包含ASEPTROL S-Tabl〇顆粒之試樣中所觀察到之細胞 毒性的原因。 試樣12、14、15及18之共同特徵為無一者含有亞氯酸根 陰離子。因此,試樣12、14及18中無一者含有氧-氯陰離 子。歸因於Cl〇2之分解,包含純口…之試樣15可能會含有 某些氧-氣陰離子在形式上為可能的,然而該量為無足輕 重的。 蜜於此等結果’推斷氧-氣陰離子為構成在此等實驗中 所觀察到之細胞毒性之基礎的成因。 實驗實例3:細胞毒性分析 141702.doc •42- 201113042 實驗實例1中之數據指示氧-氯陰離子之細胞毒性為劑量 依賴性的。特定言之’在具有最多〇·2 „^亞氯酸根陰離子/ 公克凝膠之凝膠中未觀察到細胞毒性,而在具有最多〇.5 ^^亞氯酸根陰離子/公克之凝膠中觀察到細胞毒性。設計 此貫驗以使用亞氯酸鈉溶液來進一步檢查亞氣酸根陰離子 之細胞毒性’其容許更精確估計所測試稠化流體组合物中 之亞氯酸根陰離子濃度。另外,亦評定含有i 〇%過氧化氫 作為漂白劑之市售商品的以過氧化物為主之牙齒美白產品 之細胞毒性。 藉由在使用之前不久將亞氣酸鈉水溶液與基質凝膠組合 來製備試樣22-24。因此,試樣22-25中無一者含有二氧化 氣。此等試樣亦不含有酸來源或游離鹵素來源。藉由將亞 氣酸鈉水溶液與基質凝膠混合30秒,將試樣加蓋且在室溫 下使其靜置5分鐘’再混合30秒來製備試樣22-24。類似地 但使用水代替亞氯酸鈉溶液來製備試樣25。試樣22-25中 無一者含有酸來源或游離鹵素來源。 試樣26為市售(OTC)產品,其為含有10%過氧化氫之凝 膝,凝勝材料以提供於羯包裹條帶上之形式使用。 使用藉由使ASEPTROL S-TablO錠劑於水中反應所製備 之實質性純二氧化氯溶液來製備試樣21。特定言之,使一 個1.5 mg錠劑在200 ml HA中反應。不在所得二氧化氯溶 液中通氣。如使用Hach 2010型iiv-vis分光光度計所評定, /谷液之二氧化氯濃度為約733 ppm。因此,在以2份凝膠稀 釋1份溶液之後,試樣21具有約244 ppm C102。 141702.doc •43· 201113042 細胞毒性結果展示於表8中。 表8 試樣編號 凝膠 每凝膠之亞氯酸鎂 USP<87>之結果 21 CMC 0 (以約7〇0 ppm C102溶液製成) 合格 22 0.04 合格 23 1.0 不合格 24 2.0 不合格 25 0 合格 26 未知 具有10%過氧化氫之OTC產品 不合格 陽性對照 不合格 陰性對照 合格 試樣22-24之結果指示高濃度下之亞氣酸根陰離子對人 類細胞具有細胞毒性,從而證實實驗實例2之結論。試樣 21之結果指示可使用利用ASEPTROL S-TablO錠劑製備之 實質性純二氧化氣溶液來製備非細胞毒性之高二氧化氯濃 度稠化流體組合物。 此數據亦展示1 〇% H2〇2對哺乳動物細胞具有細胞毒性 (試樣26)。實際上,反應性區域延伸超過凝膠樣本1 cm以 上,表明重度細胞毒性。 實驗實例4 :其他細胞毒性研究 為進一步檢查細胞毒性與稠化流體組合物中之氧-氯陰 離子濃度之間的關係,執行以下實驗。 藉由在使用之前不久將亞氯酸鈉水溶液(10 ml)與20 g基 質凝膠(水合高黏度NaCMC)組合來製備試樣27-31。 NaCMC 為自 Spectrum Chemical 獲得之 USP 級 CMC(物料編 號CA194) ; 1%水溶液具有約1500-3000 cp之黏度。每30 g 最終組合物使用0.85 g之NaCMC來製備基質凝膠以便達成 141702.doc • 44· 201113042 與自Sigma Aldrich獲得之CMC之彼流變能力等效之流變能 力。試樣27-30中無一者含有二氧化氣。類似地但使用水 代替亞氣酸鈉溶液來製備試樣27。藉由將亞氣酸鈉水溶液 (或水)與基質凝膠混合直至均質來製備試樣26-30。 使用兩注射器式混合方法來製備具有與試樣6相同之相 對組成及約40 ppm二氧化氯之試樣3 1。一個注射器含有-40篩目ASEPTROL S-Tab2顆粒(p.048 g)。第二注射器含有 基質凝膠(10公克)。兩個注射器之内容物如下組合。含有 顆粒之注射器保持端部朝上。移除出口插塞且連接耐綸連 接器。將耐綸連接器之另一端連接至含有基質凝膠之注射 器之出口。將凝膠注射器之柱塞缓慢壓下,將凝膠排出至 顆粒中。隨後容許凝膠及顆粒混合物擱置5分鐘以活化顆 粒,從而生成二氧化氯;在此期間,注射器保持連接。在 5分鐘之後,將注射器柱塞以迅捷速率交替地壓下以在兩 個注射器筒體之間往返移動混合物至少15次,或直至試樣顏 色均勻為止。隨後凝膠準備用於USP<87>之瓊脂擴散測試。 細胞毒性測試之結果展示於表9中。 表9 試樣編號 凝膠 每凝膠之亞氯酸鎂 USP<87>之結果 27 CMC 0 合格 28 0.1 合格 29 0.2 不合格 30 0.4 不合格 31 0.2* 合格 陽性對照 不合格 陰性對照 合格 *可能存在之最大量之亞氯酸根陰離子;如實驗實例1中所描述計算 141702.doc -45- 201113042 此專數據進一步支持亞氣酸根陰離子以劑量依賴性關係 對人類細胞具有細胞毒性的發現。每公克最終組合物含有 0.2 mg亞氯酸根之試樣29測試不合格,而每公克含有〇」 mg亞氯酸根陰離子之試樣2 8合格。此表明每公克組合物具 有小於0.2 mg亞氯酸根陰離子之二氧化氣組合物對人類細 胞為非細胞毒性的。此結果亦支持存在於以ASEpTR〇L顆 粒或粉末製成之凝膠中之亞氯酸根陰離子在二氧化氯之生 成中消耗的預期。特定言之,發現使用ASEpTR〇L顆粒或 粉末所製備且每公克最終組合物具有〇.2 mg最大可能量之 亞氯酸根陰離子的凝膠為非細胞毒性的。因此,此等凝膠 中之亞氣酸根陰離子之表觀濃度估計為小於〇 2 mg亞氯酸 根/公克。 實驗實例5:牙齒美白 在以下貫驗中評定含有二氧化氣之CMC凝膠之牙齒美白 功效。凝膠之組成實質上與表3中之試樣6之彼組成相同, 具有約0.2毫克/公克最終凝膠組合物之最大可能亞氣酸根 陰離子濃度及約40 PPm Cl〇2。實驗實例!中之結果揭示此 組合物為實質上非細胞毒性的。 現在描述用於此實驗中之材料及方法。 顏色評定:用以評定牙齒色調之兩種方法:U藉由viu 傳統比色板之目視評定;及2)分光光度測定法。亦執行數 位成像及數位影像分析以量測牙齒影像之顏色。 藉由Vita傳統比色板之目視評定:藉由與標準Vha比色 板直接比較來評定初始基線色調及隨後色調變化。Vita比 141702.doc -46- 201113042 色板按以下順序(如製造商所推薦)排列以便進行值評定: B1^A1*B2*D2*A2*C1^C2*D4*A3*D3*B3*A3.5WC3*A4 ,其"1為最亮且以為最暗。兩個調查者藉由在受 控、標準化勞光條件下,相對於標準化黑色背景目測個體 牙齒來判定最接近之色輕配。在所選美白實驗中,在距 測試樣本之以距離處使用掌上型LED照明設備來使背景 光條件標準化。操作者之間在色調選擇方面之—致程度大 於80%色調選擇之不_致決不大於1個色調值單位⑽ value unit,SVU) ° 分光光度測定法:臨床分光光度計Vha EasyShade⑧ ('dent,Brea, CA)用以基於ciELAB L*a*b*色空間獲得關 於色調量測及特定顏色量測參數之電子、定量數據。在此 3d色空間系、统巾,「L」為物體之亮度(範圍介於黑色至白 色)且為可單獨存在之唯一色維度;「a」為紅色或綠色之 畺度,且「b」為黃色或藍色之量度。裝置使用具有65〇〇 度色溫(以克耳文(Kelvin)為單位)之D65光源。在任何美白 處理結束時,測定且記錄△[、△&及Ab值。 數位影像.使用SLR數位相機/顯微鏡(具有〇ptjva變焦 1〇〇透鏡附件之Olympus DPII數位相機/顯微鏡)拍攝牙齒之 數位影像。所有影像以標準手動輸入之設定來獲得β閃光 器之近似固定照明經組態以提供最佳、標準化成像條件。 試樣以固定位向重複地轉換角度或定向以確保可重現之影 像對準。 天然污染之牙齒:具有D4或更低(亦即D4至C4)之内在 141702.doc -47· 201113042 内部污染之人類牙齒用作天然污染之牙齒。將牙齒切開, 隨後如下所述製備。 茶葉污染之牙齒:如下使具有大於D4(亦即81至〇2)之内 在色調值之人類牙齒進行以茶葉為主之人工染液。切開牙 齒之後,將曝露之齒質表面以碳化矽紙拋光。隨後將齒質 表面以37%磷酸蝕刻凝膠蝕刻2〇_25秒,以水沖洗3〇秒,且 吸乾至濕潤齒質條件。隨後使牙齒進行連續污染循環(藉 由浸泡於濃茶葉染液中)直至污潰強度(stain intensit幻在目 視檢查下顯得未變化(通常在C4_A42 vita色調範圍中)為 止。 … 如下製備余葉污染及天然污染之牙齒以便處理。牙齒之 曝露齒質表面以透明指曱油之三層獨立塗層塗布;在塗覆 下一塗層之岫使每一塗層乾燥至少一小時。隨後在測試之 前將牙齒置放於自來水中至少24小時。在開始處理之前, 藉由定性及定量顏色評定來評定基線牙段色調。將牙齒以 近遂心位向安裝於玻璃顯微鏡載片中。在處理期間以及在 處理之間,將牙齒在100%濕度下儲存於塑膠袋中。在美 白檢定期間,將牙齒自塑膠袋移除,徹底地沖洗以移除處 理或對,日,?、美白劑,且隨後進行定性及定量顏色評定。 非細胞毒性Cl〇2凝膠:實質上如對於試樣6所描述來製 備所測試之非細胞毒性Cl〇2水性凝膠材料。簡言之,藉由 將0.85公克高黏度羧甲基纖維素鈉粉末添加至2915公克蒸 德水來製備3 0公克之水性凝膠基質。容許混合物水合至少 約8小時’隨後混合以使基質凝膠均質化。向容器中之約 141702.doc -48- 201113042 30公克水性NaCMC基質凝膠中添加〇_143公克ASEpTR〇L S-Tab2顆粒(-40篩目)且徐緩地混合3〇秒。隨後將容器緊密 地加蓋且容許混合物在室溫下靜置約5分鐘。隨後將其短 暫地再混合且隨後Cl〇2凝膠準備使用。 最終凝膠之大多數組份之濃度可自質量平衡計算或已經 量測。組份概述於表10中。剩餘組份為:藉由pH 7滴定法 之約40 PPm Cl〇2及小於約110卯爪未反應之亞氣酸根陰離 子(C102)。 表10 化學物質 NaCMC 水 Na+ Mg+2 Cl- S04_2 =聚氰酸 濃度,重量% 2.8% 96.7% 0.10% 0.048% 0.26% 0.047% 0.002% 所製備Cl〇2凝膠為透明至半透明之淡黃色的黏性假塑性 流體。其具有足以當以1 -2 mm層形式塗覆於牙齒時保持其 形狀,但足夠低以藉由擦拭實質上自牙齒表面及口腔軟組 織移除之屈服點。凝膠可溶於額外水中且可經由沖洗戋灌 溉而自口移除。雖然α〇2不安定且隨時間過去緩慢分解, 但是在適當儲存條件(保持於密閉容器中,緊密地加蓋或 密封,且最小程度曝露於紫外光輻射)下經8小時之濃度損 失小於20%。 處理:混合之後,將Cl〇2凝膠抽取至60 ml塑膠注射器 中。60 ml注射器用以在檢定期間固持凝膠,且用於將凝 膠施配至10 ml塑膠注射器中。隨後如下將1〇 ml注射器中 之凝膠直接施配於牙段琺瑯質表面上。在零時,將約i至 1.5 ml凝膠施配於附著於玻璃顯微鏡載片之每一牙段之琺 141702.doc -49- 201113042 鄉貪表面上°所得凝膠層之厚度為約1.5至3.0 111111深。將 凝膠施配於牙段上之後,將玻璃載片置放於15 mmx8 mm 塑膠Ziplock®袋(sc Johnson Co” Racine,WI)中,在袋内含 有濕紙巾之小條帶以維持袋中之1〇〇c/。濕度。將紙巾條帶 定位以消除塑膠袋與牙齒及凝膠表面之任何接觸。 在測試間隔(通常15分鐘)結束後,將玻璃载片自塑膠袋 取出,且以特軟鬃牙刷及輕微流動之自來水流謹慎地移除 凝膠。隨後分析载片上之牙段之色調及顏色,纟此期間定 期將玻璃載片維持於1〇〇%濕度下之塑膠袋中以避免由脫 水產生之不當橋作顏色。 按設計重複凝膠施加程序直至實驗結束。在100%濕度 下,將所測試牙段儲存於玻璃顯微鏡載片上用於稍後參考 觀察。 將天然 >可染及茶葉污染之人類牙齒以C102凝膠處理總共 1小時(4-15分鐘連續處理)。將單一批料之α〇2凝膠用:: 等連續處理。為進行對比,將其他茶葉污染之牙齒以含有 10%氫之市售美白產品處理。根據製造商說明書,以OTC 產品處理由30分鐘處理組成。在處理結束時,取出條帶之 後留在牙齒上之殘餘0TC產品使用軟鬃牙刷及輕微流動之 水流自牙齒移除。對於使用OTC產品之多天處理(例如7、 1〇及I4天)而言,通常一個3〇分鐘處理發生於早晨且第二 個30分鐘處理發生於晚上。 個別牙齒在基線下以及以C1〇2凝膠處理4><15分鐘(總共 60分鐘)之後的Vita色調值列入表丨丨及^中。由於以凝 141702.doc •50· 201113042 膠處理,六個茶葉污染之牙齒中之一者及六個天然污染之 牙齒中之一者各自達成B1。 表11茶葉污染之牙齒 樣本 基線色調 處理後色調 SVU Γ1 A4 C1 9n 12 T3 C2 C4 — B1 6.0 A3 _ 7.0 T4 A3 ~~ A2 Q Λ T5 D3 A2 V.U T6 5.0 A4 D2 11.0 表12天然污染之牙齒 樣本 基線色調 處理後色調 SVTT Nl A3-D3 D2-A2 > 4 η N2 - A3.5-B4 B2 L ^ H.U >9.0 XT/t A3 B2-A1 >6.0 JN4 N5 A3 A3 B2-A1 R1 >6.0 N6 B4 A2 8.0 8.0 如圖1中所示,非細胞毒性之含有cl〇2之凝膠對茶葉污 染之牙齒(n=6)處理30分鐘(2x15分鐘)之後,總色調變化大 大咼於5個色調值單位_Vita(svu)。對於天然污染之牙齒 (n=6)而言,總色調變化超過6 svu。處理45分鐘(3X15分 鐘)之後’天然污染之牙齒之總色調變化為約7 svu。以 ASEPTROL凝膠處理茶葉污染之牙齒1小時(4><15分鐘)之 後,平均總色調變化為7.83 SVU。以非細胞毒性ci〇2疑膠 處理之天然污染之牙齒之總色調變化大約相同。 非細胞毒性之含有Cl〇2的凝膠在前丨5分鐘處理之後顯著 7C白天然污染之牙齒,且隨著處理持續,亮白亦持續。相 比之下,以含有1 〇%過氧化氫之〇TC組合物處理天然污染 之牙齒展示低得多的亮白程度。在前3〇分鐘處理之後,觀 141702.doc -51 · 201113042 察到適度改良(1 SVU)且在第二個30分鐘處理之後無統計 上顯著的變化。遵循0TC產品製造商推薦之歷時7天每天2χ 30分鐘處理(總處理時間為7小時)引起顯著的改良(總色調 變化為4.9 SVU);然而,與Cl〇2組合物連續處理4χΐ5分鐘 (總處理時間為i小時)之後相比,牙齒美白之改良明顯較 少。以OTC產品處理10天(每天2><3〇分鐘;總處理時間為 1〇小時)獲得6.1 SVU之總色調變化。需要以含有1〇%過氧 化氫之otc組合物處理14天(總處理時間為14小時)以產生 可與藉由非細胞毒性C1〇2凝膠在一小時處理中所達成之總 色調變化相當的總色調變化。因此,與過氧化氫為主之組 合物相比,含有C1〇2之凝膠在顯著較短時間中提供更大亮 白程度。此外,含有Cl〇2之凝膠調配物為非細胞毒性的, 而10%過氧化氫調配物為細胞毒性的(參見實驗實例3)。 以含有C1 〇2之凝膠處理總共!小時之茶葉污染之牙齒的 平均AL值為9.3 ; 6個樣本之值範圍為〇 8至22AL單位。以 含有Cl〇2之凝膠處理總共i小時之天然污染之牙齒的平均 AL值為8_〇7。以含有1〇%過氧化氫之〇TC組合物處理總共7 小時總處理時間之牙齒的平均亮度變化為6.32 AL單位。 因此,非細胞毒性之含有cl〇2之凝膠在漂白茶葉污染之 牙齒及天然污染之牙齒中極為有效。在前15分鐘處理之 後,偵測到顯著亮白改良。在僅以含有Cl〇2之凝膠處理兩 個15刀鐘之後所達成之亮白程度需要以含有10%過氧化氫 之OTC美白產品每天2)<3〇分鐘處理7天來達成。在以含有 ci〇2之凝膠處理四個15分鐘之後所達成之亮白程度需要以 141702.doc •52· 201113042 含有10%過氧化氫之〇TC組合物處理1〇天以上來達成。 實驗實例6 :含有C丨ο:之凝膠相對於36%過氧化氫之功效 α又计此K 以比較非細胞毒性含有cl。〗之凝膠與含有 36%過氧化氫之專業診療椅邊美白凝膠之牙齒美白功效。 此為當前用於專業診療椅邊產品中之過氧化氫之最高濃 度。如實例5中所述製備含有〇1〇2之凝膠且處理程序與實 例5中相同。 結果概述於圖2争。45分鐘處理之後,非細胞毒性含有 Cl〇2之凝膠(約40 ppm ο%)之美白功效接近專業凝膠之彼 美白功效。如在此項技術中所熟知,含有36%過氧化氮之 凝膠對於口腔中之軟組織為高度刺激性的。因此,在不存 在軟組織刺激的情況下達成相當牙齒美白功效為高度合意 的且對於先前技術產品而言為不可能的。 在市昜上存在夕種由牙科專業人員使用之專業牙齒美白 產品。如同市售產品’專業產品以過氧化物為主。此等產品 之功效數據可在文獻中獲得(例如參見〇{^心Denti_, ,4· 322 327)。文獻值表明比過氧化物輕微得多的 你白齊J gp非細胞毋性的含有ci〇2之凝膠接近許多以過氧 化物為主之專業產品的功效,且在某些情況下可超過以過 氧化物為主之專業產品的功效。 實驗實例7 ··琺螂質及齒質之顯微硬度 已知過氧化氫會不利地影響牙齒硬組織。牙齒敏感性為 專業牙齒美白產品之當目5丨丨从^ 卜 之吊見W作用且咸信起源於由高濃度過 氧化物誘導之琺螂質及產曹 M貝的形態變化。許多專業產品推 141702.doc •53· 201113042 薦使用氟化納使牙齒再礦物化且使用硝酸鉀以降低牙齒敏 感性。為特徵化非細胞毒性含有Cl〇2之凝膠對於J法鄉質及 齒質之效應’在與含有二氧化氯之凝膠接觸前後評定珠鄉 質及齒質之顯微硬度及粗糙度。 含有Cl〇2之凝膠之組成與實驗5中之組成相同。對於使 用含有Cl〇2之凝膠及含有10% H2〇2之市售產品(〇TC)之琺 瑯質及齒質實驗而言,總處理時間為7小時,由14χ3〇分鐘 處理組成》製備多個批料之含有cl〇2之凝膠且將其用於此 貫驗中。含有Cl〇2之凝膠批料使用不超過2小時。7小時總 處理時間與OTC產品推薦處理時間相同。然而,此總處: 時間極大地超過非細胞毒性二氧化氯組合物達成與0TC或 專業以過氧化物為主之產品相當之牙齒美白所需要之時間 γ參見實例5及6) ^對於包含36%過氧化氫之專業牙齒美白 凝膠而言’接觸限於-小時。在處理之前、期間及之後, 牙齒樣本儲存於自來水中。 便用CSM動態顯微硬度測試 士“ 丁 T只月秋、 载/30秒卸載下評定顯微硬廑。 ^ β式五個i法瑯質樣本及 個嵩質樣本之顯微硬度變化。每—樣本充當其自身對照 (處理前與處理後相比Ρ對於链螂質硬度而言,每一樣 ^處理前及處理後進行十次量測。ϋ此,存在50個處理 1測值及50個處理後量測值。 丄上 m 對於齒質硬度而言,每一 本在處理前及處理後進行 n 人里測,獲得25個處理前量 值及25個處理後量測值。 硬度數據以維氏(Vick㈣ 度值來计异。統計分析由 仗用ϋ.〇5 α水準之ANOVA(單 141702.doc •54. 201113042 子)組成。 琺瑯質硬度(以維氏硬度值計)之結果展示於表13中。 表13 組合物 處理前 處理後 P值 統計顯著性 (p<0.05) C102-凝膠 498.89 ±70.64 507.40 ± 69.92 0.5090 否 OTC產品 711.57 士 114.56 722.84 ± 14L85 0.8474 否 36% H2〇2 538.56 ± 109.30 455.72 ±36.62 0.000768 是 含有C102之凝膠或10% H202產品皆未誘導琺瑯質硬度之 統計上顯著變化。相比之下,專業產品誘導琺瑯質硬度之 統計上顯著降低(> 15°/。降低)。因此,非細胞毒性含有C102 之凝膠以與甴專業過氧化物凝膠誘導之彼功效相當之功效 美白牙齒,但不會不利地影響琺瑯質硬度。 齒質顯微硬度(以維氏硬度值計)之結果展示於表14中。 表14 組合物 處理前 處理後 P值 統計顯著性 (ρ<0·05) C102-凝膠 94.96 ±9.63 87.65 ±6.69 0.0031 是 OTC產品 98.35 ± 15.14 88.71 ±6.02 0.0118 是 36% H2〇2 101.50±21.48 83.45 ± 11.97 0.002212 是 關於齒質顯微硬度,含有cio2之凝膠誘導齒質顯微硬度 之較小(7.7%)降低,其為統計上顯著的。市售(OTC)產品 (10%過氧化物)顯示齒質顯微硬度之類似較小(9.8%)降 低,其亦為統計上顯著的。值得注意地是,專業凝膠在僅 一小時之總接觸時間後誘導齒質之驚人(約18%)降低。 因此,包含有效用於牙齒美白之量之二氧化氣之非細胞 毒性組合物對於琺瑯質顯微硬度不具有統計上顯著效應且 141702.doc -55- 201113042 對於齒質顯微硬度僅具有較小效應。對於齒質顯微硬声之 效應與由市售牙齒美白產品誘導之彼效應相當。 實驗實例8:琺瑯質及齒質之表面粗糙度 已表明粗糙度增加會導致表面積增加,從而造成美白牙 齒之反彈。為研究非細胞毒性之含有二氧化氯之組合物對 於表面粗链度之效應’使用Surftest 1700表面輪靡儀來^平 定以各種美白組合物處理前後琺瑯質及齒質之表面粗糙 度。 ^ 測試四個珠瑯質樣本及四個齒質樣本。每一樣本充备其 自身對照。每一樣本在處理前進行12次量測且每一樣本在 處理後再進行12次量測。含有C1〇2之凝膠之接觸時間為總 共2.5小時,由4_15分鐘處理及3_3〇分鐘處理組成。再以含 有Cl〇2之凝膠處理3〇分鐘直至達成7小時之總處理時間。 在處理之前、期間及之後,將樣本儲存於自來水中。非細 胞毋性之含有二氧化氯之組合物與用於實驗實例8中之彼 組。物相同。亦在14_3〇分鐘連續處理中測試含有過氧 化氫之市售(0TC)美白產品。亦測試含有娜過氧化。^ 專業牙齒美白凝膠。對於專業牙齒美白凝膠而* 热一 ί ΐ 〇 钱觸限 / 。統計分析由使用0.05 α水準之AN〇Va(單因子) 產 :卜細胞毒性二氧化氯組合物及含有1 〇 %過氧化氯之〇 T c ασ之表面輪廓測定數據展示於表1 5中。 141702.doc •56_ 201113042 表15 Ra值 ANOVA Ρ值 處理月ϋ 處理後 2.5小時 7小時 2.5小時 7小時 琺瑯質 OTC 0.037692 ± 0.00914 N/D 0.048742 ±0.0157 N/D 0.04674* Cl〇2 0.024975 士 0.002445 0.021508 ± 0.000888 0.02295 士 0.000666 0.005799* 0.048636* 齒質 OTC 0.032053 ± 0.007332 N/D 0.051742 ±0.00882 N/D 0.0000053* Cl〇2 0.03998 ± 0.005542 0.03775 ± 0.00466 0.044608 土 0.00392 0.296884 0.027545* N/D=未測定。 *統計上顯著的 链瑯質之平均表面粗糙度Ra在以非細胞毒性二氧化氡組 合物處理之前為約0.025且在處理2.5小時之後為0.021,且 在處理7小時之後為約0.023。因此,未偵測到含有C102之 凝膠對於琺瑯質平均表面粗糙度之反效應,甚至不論是否 長期接觸持續時間亦如此。實際上,在此實驗中,在以含 有C102之凝膠處理2· 5小時之後,琺瑯質平均表面粗糙度 事實上更平滑約13-14%,指示在不存在研磨劑的情況下出 乎意外之琺瑯質拋光效應。此外,2.5小時處理之後對於 齒質平均表面粗糙度之效應為非統計上顯著的。處理7小 時之後,齒質平均表面粗糙度僅增加約8°/。。如先前提 及,7小時之處理超過以此組合物達成與OTC或專業以過 氧化物為主之產品相當的牙齒美白所需要之時間(參見實 例5及6)。因此,非細胞毒性二氧化氯組合物可產1與 OTC或專業產品相當之牙齒美白而不會實質性損傷琺郫質 或齒質表面粗綠度。 相比之下,在所推薦之7小時接觸時間之後,OTC產品 141702.doc -57- 201113042 王爱 CL. _ 比— ,回展示琺瑯質表面粗糙度增加大於約29〇/0。7小 時之:,齒質表面粗糙度增加大於6〇%。僅處理】小時之 ^ 有36/°過氧化氫之專業過氧化物產品使琺螂質及齒 貝兩者之表面粗糙度增加約203 %。 關於對於珠瑯質之效應,與未經處理之對照牙齒(圖3a) 相比,在以非細胞毒性之含有cl〇2之凝膠處理7小時之樣 本(圖3B)中觀察到極少表面形態變化跡象。實際上,精細 處理到痕(牙齒樣本製備之結果)仍為明顯的。相比之下, 以36%過氧化物凝膠處理一小時之樣本(圖3c)之像片顯示 琺瑯質變化且可能腐蝕之相當大的區域。 圖4 A中所示,對照(未經處理)牙齒之齒質表面形態具 有曝露或顯示之某些齒質小管,且其他齒質小管由齒質塗 抹層(smear layer)遮蓋。某些塗抹插塞(81^^ plug)明顯處 於曝露小管内。與未經處理之對照齒質表面相比,以含有 ίο/。H2〇2之OTC產品處理之代表性樣本之表面(圖4B)顯示 更大數目之曝露齒質小管。與對照表面相比,曝露小管在 某種程度上顯得放大,且在不存在封閉塗抹插塞的情況下 許多小管顯得敞開。與對照表面相比,以非細胞毒性之含 有Cl〇2之凝膠處理之代表性牙齒樣本(圖4C)具有所曝露或 顯示之更大數目之齒質小管;但與存在於〇TC處理樣本令 之小管相比,數目較少’且尺寸較小。曝露小管以具有有 限開口之較窄「缝隙(slit)」形式存在;某些齒質小管由明 顯塗抹層遮蓋;某些塗抹插塞明顯處於曝露小管内。因 此’以非細胞毒性之含有Cl〇2之凝膠處理之牙齒表面更接 H1702.doc -58- 201113042 近地類似於對照牙齒表面β 雖然不希望受理論約束,但是咸㈣㈣過氧化氫凝膠 所誘導,且因此預期可見於較高濃度專業產品之齒質表面 變化可至少部分地構成市售商品及專業過氧化物美白產品 中之常見牙齒敏感性問題的基礎。 實驗實例9:臨床試驗 此人類個體可行性研究之目的為評估珍療椅邊、】小時 ㈣獨立15分鐘處理)、珍療所内施用包含約4。ppm二氧 化氣及高黏㈣甲基纖維素納作相化劑組份的非細胞毒 性牙齒美白組合物之功效。組合物包含不超過約〇 2叫氧_ 氣陰離子/公克組合物。評估色調變化及對於牙齒增白劑 之牙齒敏感性以及患者對於處理之反應。15名個體參與臨 床試驗。在此試探性、單臂、非對照、前瞻性、病例對照 研九中個體接文貫驗性牙齒增白劑之1小時(4次獨立! 5 分鐘處理)、診療所内處理。所有個體在基線時、診療所 内處理之施用後即刻、施用後72小時,及診療所内處理之 施用後一週受到監測。受訓檢查者使用vha(vita Zahnfabrik)比色板及彩色透明片監測顏色變化^ 匕色 板為一種包括於ADA準則中之可接受之評估方法。透明片 用作顏色後:化之記錄。在基線時、診療所内處理後即刻、 «乡療所内處理後72小時及診療所内處理後一週使用供患者 作標記之標準化量表來監測牙齒敏感性。 如藉由與值導向之Vita比色板進行比較所判定,基於具 有為A3或更暗之Vita色調之上頜前牙來選擇個體。個體必 141702.doc •59· 201113042 須為18-65歲’具有良好一般健康狀態,且具有良好牙齒 保健及口腔衛生。研究中不包括具有進行中的齲齒、牙周 病、前齒冠較大或修補、先前經漂白或四環素污染之牙齒 的患者。 在參與到研究中後’每一患者由一個臨床醫師檢查。基 線Vita色調由兩個評估器測定;六個測試上頜前牙及六個 對照下頜牙之一致色調由牙科醫師記錄。以1:丨放大率製 得數位彩色透明片(Ph〇tomed si Pro數位臨床相機_Fuji Body; Sigma Lens; Nikon Flash)。對應之viu比色條(3}ι_ tab)包括於像片中。 製得上頜弓之海藻酸鹽印模且注入牙科用硬質石膏中。 使用製造商推薦之材料及設計來製造每一患者之定製美白 牙托。在開始處理之前,所有個體接受預防且要求其對標 準化量表作標記以評價基線敏感性。 已開始臨床試驗,且已獲得初步數據。 貫施方式中引述之每—專利、專利中請案及公開案之揭 示内容據此以全文引用的方式併入本文中。 雖然已參考特定實施例揭示組合物、套組及其使用方 法,但疋顯然熟習此項技術者可在不背離組合物、套組及 使用方法之真實精神及範_的情況下設計出其他實施例及 變化。意欲將附加巾請專利範圍解釋為包括所有該等實施 例及等效變化。 【圖式簡單說明】 圖1為描述非細胞毒性之含有cl〇2之組合物及具有肌 141702.doc 201113042 過氧化氫之商業市售(OTC)產品與總處理時間關係曲線之 牙齒美白數據的直方圖。cio2=非細胞毒性之含有C102之 組合物之數據。〇TC=具有10%過氧化氫之商業產品之數 據; 圖2為描述非細胞毒性之含有C102之組合物與包含36% 過氧化氫作為漂白劑之專業美白凝膠相比之牙齒美白敫據 的圖; 圖3A-3C為琺瑯質表面在2500X放大率下之一系列代表性 掃描電子顯微術(SEM)顯微照相顯微鏡照相術影像 (microphotograph photomicrography image)。圖 3A為未經 處理牙齒的琺瑯質。圖3B為經非細胞毒性之含有C102之組 合物處理之後的琺瑯質表面。圖3C為經含有36%過氧化氫 之專業美白凝膠處理之後的琺瑯質表面;及 圖4A-4C為齒質表面在5000x放大率下之一系列代表性 SEM顯微照相影像。圖4A為未經處理牙齒的齒質。圖4B 為經含有10%過氧化氫之OTC美白凝膠處理之後的齒質表 面。圖4C為經非細胞毒性之含有C102之組合物處理之後的 齒質表面。 141702.doc •61 -LSI 141702.doc •37· 201113042 Toxicity (Level 2), the sample is considered to meet the test requirements. Samples exhibiting 3 or 4 reactivity during 48 hours were considered to be cytotoxic. Table 4 Description of Grade Reactive Reactivity Zones 0 No detectable area around or below the sample 1 Some malformed or degraded cells below the slight sample. 2 Mildly limited to the area under the sample area 3 Moderate area extends beyond the sample 0.5 to 1.0 cm 4 The severe region extends over 1.0 cm above the sample. In this experimental example, the test volume for each of the prepared examples was about 0.1 cc. The results are shown in Table 5. Table 5 Sample No. Gel Type Magnesium sulfite maximal test result per gram of gel 1 S 0 Qualified 2 0.2 Qualified 3 0.5 Unqualified 4 2.0 Unqualified 5 C 0 Qualified 6 0.2 Qualified 7 0.5 Unqualified 8 2.0 No Qualified Positive Controls Unqualified Negative Controls Qualified samples 1, 2, 5, and 6 met the USP in vitro bioreactivity criteria, indicating biocompatibility. Samples 3, 4, 7 and 8 did not meet the requirements of the USP in vitro bioassay. Thus, in this experiment, the maximum concentration of chlorite anion greater than about 0.2 mg of the sulphonate anion per gram of gel produced a cytotoxic effect. These data indicate that cytotoxicity is associated with the presence of certain other components of the dioxide gas, oxy-aerobic anion or S-TAB2 particles in a dose dependent manner. 141702.doc -38- 201113042 Experimental Example 2: Cytotoxicity assay To confirm that cytotoxicity is induced by oxy-chlorine anions rather than other potentially toxic components, the following experiment was performed. A series of samples were prepared to test the effects of various ingredients or conditions in inducing cytotoxicity. ASEPTROL S-TablO tablets were used to prepare certain samples in this experiment. The chemical composition of the tablet is shown in Table 6. ASEPTROL S-TablO tablets are prepared substantially as described in Example 5 of U.S. Patent No. 6,432,322. Table 6 Component % (wt/wt) Sodium chlorite 26% Sodium dichloroisocyanurate 7% Sodium hydrogen sulphate 26% Sodium chloride 20% Magnesium chloride 21% All samples contain NaCMC as the thickener component . Samples 9, 16, and 17 were prepared using a 40-mesh portion of the pellet prepared from the ASEPTROL S-Tab 10 tablet. Samples 10, 19 and 20 were prepared using the ingredients of the ASEPTROL S-TablO tablet in a non-granulated form. Specifically, the five components were dried, dried and mixed to form a powder having the composition shown in Table 5; the powder was not compacted and granulated. Thus, Samples 9 and 10 have the same chemical composition but are made of solid components in different physical forms. Similarly, Samples 16 and 19 have the same composition as Samples 17 and 20, and Samples 17 and 20 have the same chemical composition. Samples 11-14 were prepared using a powder having a subset of the ingredients in the ASEPTROL tablet, with one or more of the ingredients being replaced (see the second row of Table 7 for details). Sample 15 contained substantially pure C102. Sample 18 contained only 141702.doc -39· 201113042 containing NaCMC. Samples 9-14 and 16-20 were prepared as described in Experimental Examples. Briefly, samples were prepared by combining a solid portion (e.g., ASEpTR® L particles) with a matrix gel shortly before use. The matrix gel is NaCMC that is allowed to hydrate. After the solid portion was added to the matrix gel, the sample was mixed with a stainless steel or plastic spatula for 30 seconds, capped and allowed to stand at room temperature for 5 minutes. The sample was then mixed a second time for 3 seconds to homogenize the sample. The prepared sample was tightly capped until the test time ^protected sodium sulfite particles and other solid mixture containing sodium sulfite, and the prepared sample was not irradiated with strong ultraviolet light to limit ultraviolet light-induced decomposition. . The test was started no more than 2 hours after the preparation of the sample. Sample 15 was prepared using a hydrated NaCMC matrix gel and a substantially pure chlorine dioxide solution prepared on the same day that the sample was prepared and the test was started. 〇.75 g of carboxymethylcellulose nanopowder (Sigma-Aldrich, 700,00 mol weight (typical)) was added to 19 2 g of deionized water, and the mixture was allowed to stand overnight in a canned jar, and The matrix gel was prepared by mixing to homogenize the matrix 'gel. Substantially pure chlorine dioxide solution was prepared as follows: I2 ASEPTROL S-TablO linkages (1.5 g each) were placed in 1 liter of drinking tap water to produce a deep yellow source of >1000 ppm chlorine dioxide> . Air is bubbled through the bottom of the source solution at a rate of about 1 liter per minute to strip the chlorine dioxide from the source solution into the air. The resulting air filled with oxidizing gas was then bubbled through the bottom of 1 liter of deionized water to form a solution of pure oxidizing gas. Only Cl〇2 and possibly some water vapor are transferred from the source solution to the product solution. All salt components remain in the source solution. As a result, the product solution 141702.doc •40-201113042 is a substantially pure solution of C102. When the yellow color of the source solution almost disappeared, the bubbling was completed. The concentration of chlorine dioxide in a sample of substantially pure chlorine dioxide solution was analyzed using a Hach 2010 UV/Vis spectrophotometer; the substantially pure solution was found to contain 700 ppm chlorine dioxide by weight. Ten grams of 700 ppm pure dioxane solution was added to the matrix gel and mixed to produce a gel containing about 233 ppm chlorine dioxide and substantially oxy-chlorine anion. As described above, the component containing NaC102 and the prepared sample were protected from intense light to limit the ultraviolet light-induced decomposition. It also protects all anhydrous solids from exposure to water (eg ambient humidity). Test specimens were tested as described in Experimental Example 1, except that Samples 1 7 and 20 were tested at a dose of 0.04 cc instead of a dose of 0.1 cc. The test was started no more than 2 hours after the preparation of the sample. The results are shown in Table 7. Table 7 Sample No. The maximum value of chlorous acid per gram of final gel USP <87> Results 9 Prepared with ASEPTROL S-TablO particles 0.5 Unsatisfied 10 Prepared with non-granulated components of ASEPTROL S-TablO 0.5 Unqualified 11 NaDCCA replaced by cyanuric acid 0.5 Unqualified 12 NaC102 Qualified by NaCl replacement 0 13 Removal of NaDCCA 0.5 Unqualified 14 NaC102 is replaced by NaCl, and NaDCCA is replaced by cyanuric acid. 0 Qualified 15 Pure C102 (no other salt) is prepared 0.5 Qualified 16 Sample prepared with 3 times water 9 0.17 Unqualified 17 Sample 9, 0.04 cc dose on paper ingot 0.5 Failed 18 No NaCIC of particles, salt or C102 0 Qualified 19 Sample 10 prepared with 3 times water 0.17 Unqualified 20 Sample 10, 0.04 cc dose on paper key 0.5 Unqualified positive control 0 Unqualified negative control 0 Qualified 141702.doc -41 - 201113042 Samples 9-11, 13, 16, 17, 19 and 20 failed to meet the in vitro bioreactivity of usp. So 'simulated U S P < 8 7 > The dissolution test did not change the results (compare samples 1 and 19, and samples 9 and 16). The dose reduction did not change the results (compare samples 9 and 17, and sample 1) 20). These data indicate that the dose used in the test or the use of a gel with 3 times water did not play a role in the observed cytotoxicity. 5 The results of Forms 9 and 10 indicate that the physical form of the ASEPTROL component does not significantly affect cytotoxicity. The results of samples i i and 13 indicate that the presence of the gas generant NaDCC A does not significantly affect cytotoxicity. This result at least indicates that the observed cytotoxicity is not produced by gas. Samples 12, 14, 15 and 18 met the USP in vitro bioreactivity standard and indicated biocompatibility. These data indicate that cytotoxicity is not caused by a separate gelling agent (sample 18). The observation that the sample containing pure ci〇2 and no other salt 15 did not cause a cytopathic effect indicates that the gas itself is not the cause of the cytotoxicity observed in the sample containing the ASEPTROL S-Tabl(R) particles. The common feature of Samples 12, 14, 15 and 18 was that none of them contained a chlorite anion. Therefore, none of the samples 12, 14 and 18 contained an oxygen-chlorine anion. Due to the decomposition of Cl?2, sample 15 containing a pure port may contain some oxygen-gas anions which are formally possible, however this amount is insignificant. The result of this honey's inference is that the oxygen-gas anion is the cause of the cytotoxicity observed in these experiments. Experimental Example 3: Cytotoxicity analysis 141702.doc • 42- 201113042 The data in Experimental Example 1 indicates that the cytotoxicity of the oxygen-chlorine anion is dose-dependent. Specifically, no cytotoxicity was observed in the gel with the highest 〇·2 „ chlorite anion/gram gel, but observed in a gel with a maximum of 〇.5 ^^ chlorite anion per gram. To cytotoxicity. This test was designed to use a sodium chlorite solution to further examine the cytotoxicity of the sulphonate anion' which allows for a more accurate estimation of the chlorite anion concentration in the thickened fluid composition tested. Cytotoxicity of a peroxide-based tooth whitening product containing commercially available merchandise containing i〇% hydrogen peroxide as a bleaching agent. Preparation of a sample by combining an aqueous solution of sodium sulfite with a matrix gel shortly before use. 22-24. Therefore, none of the samples 22-25 contained sulfur dioxide. These samples also did not contain an acid source or a source of free halogen. By mixing the aqueous sodium sulfite solution with the matrix gel for 30 seconds, Samples 22-24 were prepared by capping the samples and allowing them to stand for 5 minutes at room temperature for a further 30 seconds. Similarly, sample 25 was prepared using water instead of sodium chlorite solution. Sample 22- None of the 25 contains an acid source or Free halogen source. Sample 26 is a commercially available (OTC) product which is a knee containing 10% hydrogen peroxide, and the gel material is used in the form provided on the crucible wrapping strip. Use by making ASEPTROL S-TablO The tablet was prepared by reacting the tablet with a substantially pure chlorine dioxide solution prepared in water. Specifically, a 1.5 mg tablet was reacted in 200 ml of HA. No ventilation was achieved in the resulting chlorine dioxide solution. For example, using Hach 2010 The concentration of chlorine dioxide in the /liquid solution was estimated to be about 733 ppm by the iiv-vis spectrophotometer. Therefore, after diluting 1 part of the solution with 2 parts of gel, the sample 21 had about 244 ppm C102. 141702.doc • 43· 201113042 The cytotoxicity results are shown in Table 8. Table 8 Sample number gel per gel magnesium perchlorate USP <87> Result 21 CMC 0 (made with approximately 7 〇 0 ppm C102 solution) Qualified 22 0.04 Qualified 23 1.0 Qualified 24 2.0 Unqualified 25 0 Qualified 26 Unknown OTC product with 10% hydrogen peroxide is unqualified The results of the control of the non-conforming negative control qualified samples 22-24 indicate that the sulphonate anion at a high concentration is cytotoxic to human cells, thereby confirming the conclusion of Experimental Example 2. The results of Sample 21 indicate that a substantially pure chlorine dioxide concentration thickened fluid composition can be prepared using a substantially pure gas dioxide solution prepared using an ASEPTROL S-TablO tablet. This data also shows that 1 〇% H2〇2 is cytotoxic to mammalian cells (sample 26). In fact, the reactive region extends more than 1 cm above the gel sample, indicating severe cytotoxicity. Experimental Example 4: Other Cytotoxicity Study To further examine the relationship between cytotoxicity and the concentration of oxygen-chlorine anion in the thickened fluid composition, the following experiment was performed. Samples 27-31 were prepared by combining an aqueous solution of sodium chlorite (10 ml) with 20 g of a base gel (hydrated high viscosity NaCMC) shortly before use. NaCMC is a USP grade CMC (Material No. CA194) available from Spectrum Chemical; a 1% aqueous solution has a viscosity of about 1500-3000 cp. The matrix gel was prepared using 0.85 g of NaCMC per 30 g of the final composition to achieve the rheological ability equivalent to the rheology of the CMC obtained from Sigma Aldrich. None of the samples 27-30 contained sulfur dioxide. Sample 27 was prepared similarly but using water instead of sodium sulfite solution. Samples 26-30 were prepared by mixing an aqueous solution of sodium sulfite (or water) with a matrix gel until homogeneous. A sample 3 1 having the same relative composition as that of Sample 6 and about 40 ppm of chlorine dioxide was prepared using a two-syringe mixing method. One syringe contained -40 mesh ASEPTROL S-Tab2 particles (p. 048 g). The second syringe contained a matrix gel (10 grams). The contents of the two syringes were combined as follows. The syringe containing the particles holds the end up. Remove the outlet plug and connect the nylon connector. Connect the other end of the nylon connector to the outlet of the syringe containing the matrix gel. The plunger of the gel syringe is slowly depressed and the gel is discharged into the granules. The gel and granule mixture is then allowed to rest for 5 minutes to activate the granules to form chlorine dioxide; during this time, the syringe remains attached. After 5 minutes, the syringe plunger was alternately depressed at a rapid rate to reciprocate the mixture between the two syringe barrels at least 15 times, or until the sample color was uniform. The gel is then ready for USP <87> agar diffusion test. The results of the cytotoxicity test are shown in Table 9. Table 9 Sample No. Gel Magnesium Chlorite per gel USP <87> Result 27 CMC 0 Qualified 28 0.1 Qualified 29 0.2 Unsatisfied 30 0.4 Unsatisfied 31 0.2* Qualified positive control failed Negative control qualified * Maximum possible amount of chlorite anion; as in Experimental Example 1 Description Calculation 141702.doc -45- 201113042 This data further supports the discovery that nitrous acid anions are cytotoxic to human cells in a dose-dependent manner. Sample 29 containing 0.2 mg of chlorite per gram of final composition failed the test, and a sample of 28 gram of chlorite anion per gram was qualified. This indicates that a gas dioxide composition having less than 0.2 mg of chlorite anion per gram of composition is non-cytotoxic to human cells. This result also supports the expectation that the chlorite anion present in the gel made of ASEpTR 〇 L particles or powder is consumed in the production of chlorine dioxide. In particular, it has been found that a gel prepared using ASEpTR® L particles or powder and having a maximum possible amount of chlorite anion per gram of final composition is non-cytotoxic. Therefore, the apparent concentration of the sulphonate anion in these gels is estimated to be less than 〇 2 mg chlorite per gram. Experimental Example 5: Teeth Whitening The tooth whitening effect of a CMC gel containing a oxidizing gas was evaluated in the following tests. The composition of the gel was substantially the same as the composition of Sample 6 in Table 3, with a maximum possible argonate anion concentration of about 0.2 mg/g final gel composition and about 40 PPm Cl 〇2. Experimental example! The results in this reveal that the composition is substantially non-cytotoxic. The materials and methods used in this experiment are now described. Color Rating: Two methods for assessing tooth color: U by visual inspection of viu traditional colorimetric plates; and 2) Spectrophotometry. Digital imaging and digital image analysis are also performed to measure the color of the tooth image. Visual assessment by Vita conventional colorimetric panels: initial baseline hue and subsequent hue changes were assessed by direct comparison to a standard Vha colorimetric plate. Vita ratio 141702.doc -46- 201113042 Swatches are arranged in the following order (as recommended by the manufacturer) for value evaluation: B1^A1*B2*D2*A2*C1^C2*D4*A3*D3*B3*A3 .5WC3*A4 , whose "1 is the brightest and the darkest. Two investigators determined the closest color match by visually measuring individual teeth against a standardized black background under controlled, standardized light conditions. In the selected whitening experiment, handheld LED lighting was used at a distance from the test sample to normalize the background light conditions. Between the operators, the degree of color selection is greater than 80%. The color tone is not selected. _ No more than 1 tone value unit (10) value unit, SVU) ° Spectrophotometry: Clinical spectrophotometer Vha EasyShade8 ('dent , Brea, CA) is used to obtain electronic and quantitative data on tone measurement and specific color measurement parameters based on the ciELAB L*a*b* color space. In this 3d color space system, the "L" is the brightness of the object (range from black to white) and is the only color dimension that can exist alone; "a" is the red or green width, and "b" It is a measure of yellow or blue. The device uses a D65 source with a 65 degree color temperature (in Kelvin). At the end of any whitening treatment, Δ[, △ & and Ab values were measured and recorded. Digital image. Digital image of the tooth was taken using an SLR digital camera/microscope (Olympus DPII digital camera/microscope with 〇ptjva zoom 1〇〇 lens attachment). All images are set with standard manual input settings to obtain an approximate fixed illumination of the beta flasher configured to provide optimal, standardized imaging conditions. The sample is repeatedly angled or oriented in a fixed position to ensure reproducible image alignment. Naturally contaminated teeth: with D4 or lower (ie D4 to C4) intrinsic 141702.doc -47· 201113042 Internally contaminated human teeth are used as naturally contaminated teeth. The teeth were cut open and then prepared as described below. Tea-contaminated teeth: Artificial teeth containing tea-based artificial dyes having a tonal value greater than D4 (i.e., 81 to 〇2) are subjected to the following. After the teeth are cut, the exposed dent surface is polished with carbonized paper. The dentate surface was then etched with a 37% phosphoric acid gel for 2 〇 25 seconds, rinsed with water for 3 sec seconds, and blotted dry to wet densit conditions. The teeth are then subjected to a continuous contamination cycle (by immersion in concentrated tea liquor dyes) until the stain strength (stain intensit illusion does not appear to change under visual inspection (usually in the C4_A42 vita tonal range). And naturally contaminated teeth for treatment. The exposed tooth surface of the teeth is coated with three separate layers of transparent finger oil; each coating is dried for at least one hour after application of the next coating. The teeth were placed in tap water for at least 24 hours. The baseline segmental tones were assessed by qualitative and quantitative color assessment prior to the start of treatment. The teeth were mounted in a near-central position on a glass microscope slide. During processing and during processing Between the teeth, the teeth are stored in a plastic bag at 100% humidity. During the whitening test, the teeth are removed from the plastic bag and thoroughly rinsed to remove the treatment or the right, the day, the whitening agent, and then qualitative And quantitative color assessment. Non-cytotoxic Cl〇2 gel: The non-cytotoxic Cl〇2 aqueous coagulation tested was prepared essentially as described for sample 6. Glue material. Briefly, 30 grams of aqueous gel matrix was prepared by adding 0.85 grams of high viscosity sodium carboxymethylcellulose powder to 2915 grams of distilled water. The mixture was allowed to hydrate for at least about 8 hours' followed by mixing Homogenize the matrix gel. Add about 143,130 grams of ASEpTR〇L S-Tab2 particles (-40 mesh) to about 141702.doc -48- 201113042 30 grams of aqueous NaCMC matrix gel in the container and slowly mix 3 Leap seconds. The container is then tightly capped and the mixture allowed to stand at room temperature for about 5 minutes. It is then briefly remixed and then the Cl〇2 gel is ready for use. The concentration of most components of the final gel can be Calculated from mass balance or measured. The components are summarized in Table 10. The remaining components are: about 40 PPm Cl〇2 by pH 7 titration and less than about 110 paws unreacted sulphonate anion (C102) Table 10 Chemicals NaCMC Water Na+ Mg+2 Cl-S04_2 = Polycyanate concentration, wt% 2.8% 96.7% 0.10% 0.048% 0.26% 0.047% 0.002% The prepared Cl〇2 gel is transparent to translucent Light yellow viscous pseudoplastic fluid. It is sufficient The shape is maintained when applied to the teeth in the form of a 1-2 mm layer, but low enough to wipe the yield point substantially removed from the tooth surface and the soft tissue of the mouth. The gel is soluble in additional water and can be irrigated via irrigation And removed from the mouth. Although α〇2 is unstable and slowly decomposes over time, under proper storage conditions (maintained in a closed container, tightly capped or sealed, and minimally exposed to ultraviolet radiation) The concentration loss in hours is less than 20%. Treatment: After mixing, the Cl〇2 gel is drawn into a 60 ml plastic syringe. A 60 ml syringe is used to hold the gel during the assay and is used to dispense the gel into a 10 ml plastic syringe. The gel in the 1 〇 ml syringe was then applied directly to the enamel surface as follows. At time zero, about i to 1.5 ml of gel is applied to each segment of the glass microscope slide. 141702.doc -49- 201113042 The thickness of the gel layer obtained is about 1.5 to 3.0 111111 deep. After the gel was applied to the segment, the glass slide was placed in a 15 mm x 8 mm plastic Ziplock® bag (sc Johnson Co" Racine, WI) containing a small strip of wet tissue in the bag to maintain the bag. 1〇〇c/. Humidity. Position the paper towel strip to remove any contact between the plastic bag and the tooth and gel surface. After the test interval (usually 15 minutes), remove the glass slide from the plastic bag and The soft toothbrush and the slightly flowing tap water flow carefully remove the gel. The color and color of the segments on the slide are then analyzed, and the glass slides are periodically maintained in a plastic bag at 1% humidity during this period. Avoid improper bridging caused by dehydration. Repeat the gel application procedure as designed until the end of the experiment. Store the tested segments on a glass microscope slide at 100% humidity for later reference. Human teeth stained with tea contaminated with C102 gel for a total of 1 hour (4-15 minutes of continuous treatment). A single batch of α〇2 gel was treated continuously with:: etc. For comparison, other teas were contaminated Teeth with 10% hydrogen commercially available whitening product treatment. According to the manufacturer's instructions, the OTC product treatment consists of 30 minutes of treatment. At the end of the treatment, the residual 0TC product left on the teeth after taking out the strip uses a soft toothbrush and a slight flow. The water flow is removed from the teeth. For multi-day treatments using OTC products (eg 7, 1 and 1 day), usually a 3 minute treatment occurs in the morning and a second 30 minute treatment occurs in the evening. Baseline and C1〇2 gel treatment 4><Vita tone values after 15 minutes (60 minutes total) are listed in Tables and Tables. One of the six tea-contaminated teeth and one of the six naturally contaminated teeth each achieved B1 due to gel treatment with 141702.doc •50·201113042. Table 11 Tooth samples contaminated with tea leaves Baseline toned color tone SVU Γ1 A4 C1 9n 12 T3 C2 C4 — B1 6.0 A3 _ 7.0 T4 A3 ~~ A2 Q Λ T5 D3 A2 VU T6 5.0 A4 D2 11.0 Table 12 Table of naturally contaminated teeth Base tone toned color tone SVTT Nl A3-D3 D2-A2 > 4 η N2 - A3.5-B4 B2 L ^ HU > 9.0 XT/t A3 B2-A1 > 6.0 JN4 N5 A3 A3 B2-A1 R1 &gt ;6.0 N6 B4 A2 8.0 8.0 As shown in Figure 1, the non-cytotoxic gel containing cl〇2 treated the tea-contaminated teeth (n=6) for 30 minutes (2x15 minutes), the total color change was greatly reduced 5 tone value units _Vita (svu). For naturally contaminated teeth (n=6), the total tonal variation exceeds 6 svu. After 45 minutes of treatment (3 x 15 minutes), the total color change of the 'naturally contaminated teeth' was about 7 svu. Treating tea contaminated teeth with ASEPTROL gel for 1 hour (4> After <15 minutes), the average total color tone change was 7.83 SVU. The total color change of the naturally contaminated teeth treated with non-cytotoxic ci〇2 suspected gel is about the same. The non-cytotoxic gel containing Cl〇2 showed significant 7C white naturally contaminated teeth after 5 minutes of treatment, and the whitening continued as the treatment continued. In contrast, treatment of naturally contaminated teeth with a 〇TC composition containing 1% hydrogen peroxide exhibited a much lower degree of whiteness. After the first 3 minutes of treatment, 141702.doc -51 · 201113042 observed moderate improvement (1 SVU) and there was no statistically significant change after the second 30 minute treatment. Followed by the 0TC product manufacturer's recommended 7-day, 2, 30-minute treatment (total processing time of 7 hours) caused significant improvement (total color change was 4.9 SVU); however, continuous treatment with Cl〇2 composition for 4 to 5 minutes (total After the treatment time was i hours), the improvement of tooth whitening was significantly less. Treated with OTC products for 10 days (2 per day) <3 minutes; total processing time was 1 hour) A total color change of 6.1 SVU was obtained. It is necessary to treat the oTC composition containing 1% hydrogen peroxide for 14 days (total treatment time is 14 hours) to produce a comparable overall color change that can be achieved with the non-cytotoxic C1〇2 gel in one hour of treatment. The total color change. Thus, a gel containing C1〇2 provides a greater degree of brightness over a significantly shorter period of time than a hydrogen peroxide-based composition. In addition, the gel formulation containing Cl〇2 was non-cytotoxic, while the 10% hydrogen peroxide formulation was cytotoxic (see Experimental Example 3). Treat a total of gels containing C1 〇2! The average AL value of teeth contaminated with tea in hours is 9.3; the value of 6 samples ranges from 〇 8 to 22AL units. The average AL value of teeth treated with a gel containing Cl〇2 for a total of i hours was 8_〇7. The average brightness change of the teeth treated with a 〇TC composition containing 1% by weight of hydrogen peroxide for a total of 7 hours was 6.32 AL units. Therefore, non-cytotoxic gels containing cl〇2 are extremely effective in bleaching tea-contaminated teeth and naturally contaminated teeth. Significant brightening improvements were detected after the first 15 minutes of treatment. The degree of whitening achieved after treating only 15 knives with a gel containing Cl〇2 requires an OTC whitening product containing 10% hydrogen peroxide per day 2) <3 minutes to 7 days to achieve. The degree of whitening achieved after four minutes of treatment with a gel containing ci〇2 was achieved by treating 141702.doc •52·201113042 containing 10% hydrogen peroxide in a TC composition for 1 day or more. Experimental Example 6: Efficacy of a gel containing C丨ο: with respect to 36% hydrogen peroxide. This K is further compared to a non-cytotoxic containing cl. 〗 The gel and the professional treatment chair with 36% hydrogen peroxide whitening gel teeth whitening effect. This is the highest concentration of hydrogen peroxide currently used in professional chairside products. A gel containing 〇1〇2 was prepared as described in Example 5 and the treatment procedure was the same as in Example 5. The results are summarized in Figure 2. After 45 minutes of treatment, the non-cytotoxic gel containing Cl〇2 (about 40 ppm ο%) has a whitening effect close to that of a professional gel. As is well known in the art, gels containing 36% nitric oxide are highly irritating to soft tissues in the mouth. Therefore, achieving comparable tooth whitening efficacy without the presence of soft tissue irritation is highly desirable and not possible with prior art products. There are special dental whitening products used by dental professionals in the market. Like commercial products, 'professional products are based on peroxides. Efficacy data for these products is available in the literature (see, for example, ^{^心Denti_, , 4·322 327). The literature values indicate that your Baiqi J gp non-cell 的 gel containing ci〇2 is much closer to the efficacy of many peroxide-based specialty products, and in some cases may exceed The efficacy of specialty products based on peroxides. Experimental Example 7 · Microhardness of tannin and dentin It is known that hydrogen peroxide adversely affects hard tissues of teeth. The sensitivity of teeth is the main cause of professional tooth whitening products. The effect of sputum from the sag of the sputum and the origin of the sputum induced by the high concentration of peroxide and the morphological changes of the Cao M. Many professional products push 141702.doc •53· 201113042 It is recommended to use fluoride fluoride to remineralize teeth and use potassium nitrate to reduce tooth sensitivity. To characterize the effect of a non-cytotoxic gel containing Cl〇2 on the J-grain and the dentin, the microhardness and roughness of the bead and dentin were assessed before and after contact with the chlorine dioxide-containing gel. The composition of the gel containing Cl〇2 was the same as that of Experiment 5. For the tannin and dentine experiments using a gel containing Cl〇2 and a commercial product (〇TC) containing 10% H2〇2, the total treatment time was 7 hours, consisting of 14χ3〇 minutes. The batch contains a gel of cl〇2 and is used in this test. The gel batch containing Cl〇2 was used for no more than 2 hours. The 7-hour total processing time is the same as the recommended processing time for OTC products. However, this total: time greatly exceeds the time required for non-cytotoxic chlorine dioxide compositions to achieve tooth whitening comparable to 0TC or professional peroxide-based products γ see examples 5 and 6) ^ for inclusion 36 In the case of professional tooth whitening gels of % hydrogen peroxide, 'contact is limited to - hour. The dental samples were stored in tap water before, during and after treatment. The CSM dynamic microhardness tester was used to evaluate the microhardness of the micro-hardness of the β-type five-method enamel sample and the enamel sample. - The sample serves as its own control (pre-treatment and post-treatment Ρ For the chain enamel hardness, each measurement is performed ten times before and after treatment. Thus, there are 50 treatments 1 and 50 After the treatment, the measured value is 丄m. For the hardness of the tooth, each sample is measured before and after the treatment, and 25 pre-processed values and 25 post-processed measured values are obtained. The Vickers (Vick) value is used to calculate the difference. The statistical analysis consists of ANOVA (single 141702.doc • 54. 201113042) using ϋ.5α level. The results of tannin hardness (in Vickers hardness) are shown in Table 13. Table 13 Statistical significance of P values after pretreatment of the composition (p <0.05) C102-gel 498.89 ±70.64 507.40 ± 69.92 0.5090 No OTC product 711.57 ± 114.56 722.84 ± 14L85 0.8474 No 36% H2〇2 538.56 ± 109.30 455.72 ±36.62 0.000768 is a gel containing C102 or 10% H202 A statistically significant change in the hardness of the tannin was not induced. In contrast, specialty products induced a statistically significant decrease in tannin hardness (> 15°/. reduction). Therefore, the non-cytotoxic gel containing C102 is equivalent to the effect of the professional peroxide gel-inducing effect, whitening the teeth, but does not adversely affect the hardness of the tannin. The results of the microhardness of the dentin (based on the Vickers hardness value) are shown in Table 14. Table 14 Composition before treatment P value after treatment Statistical significance (ρ <0·05) C102-gel 94.96 ±9.63 87.65 ±6.69 0.0031 is OTC product 98.35 ± 15.14 88.71 ±6.02 0.0118 is 36% H2〇2 101.50±21.48 83.45 ± 11.97 0.002212 is about the microhardness of the tooth, containing cio2 The gel induced a small (7.7%) reduction in microhardness of the dentin, which was statistically significant. Commercially available (OTC) products (10% peroxide) showed a similarly small (9.8%) decrease in the microhardness of the dentin, which was also statistically significant. Notably, the professional gel induced a surprising (about 18%) reduction in tooth quality after only one hour of total contact time. Thus, a non-cytotoxic composition comprising a quantity of dioxide effective for the whitening of teeth does not have a statistically significant effect on the microhardness of tannins and 141702.doc -55-201113042 has only a minor effect on the microhardness of the dentin. . The effect of microhard sound on the dentine is comparable to that induced by commercially available tooth whitening products. Experimental Example 8: Surface roughness of tannins and dentins It has been shown that an increase in roughness leads to an increase in surface area, which causes a rebound of whitening teeth. To study the effect of non-cytotoxic chlorine dioxide-containing compositions on surface roughness, the Surftest 1700 surface rim was used to determine the surface roughness of the enamel and dentate before and after treatment with various whitening compositions. ^ Test four bead samples and four tooth samples. Each sample is filled with its own control. Each sample was subjected to 12 measurements before treatment and each sample was subjected to 12 measurements after treatment. The contact time of the gel containing C1〇2 was 2.5 hours in total, and it consisted of 4-15 minutes of treatment and 3_3 minutes of treatment. The gel containing Cl 2 was then treated for 3 minutes until a total treatment time of 7 hours was reached. Samples were stored in tap water before, during, and after treatment. Non-cylindrical chlorine dioxide-containing compositions were used in the same set as in Experimental Example 8. The same thing. Commercially available (0TC) whitening products containing hydrogen peroxide were also tested in 14_3 minute continuous processing. Also tested to contain Na peroxide. ^ Professional tooth whitening gel. For professional teeth whitening gel and * hot one ί ΐ 钱 money limit / . Statistical analysis was performed by using AN 〇 Va (single factor) of 0.05 α level: surface characterization data of cytotoxic chlorine dioxide composition and c T c α σ containing 1 〇 % of chlorine peroxide are shown in Table 15. 141702.doc •56_ 201113042 Table 15 Ra value ANOVA Ρ value treatment month 2.5 2.5 hours after treatment, 2.5 hours, 7 hours, 7 hours, enamel OTC 0.037692 ± 0.00914 N/D 0.048742 ±0.0157 N/D 0.04674* Cl〇2 0.024975 ± 0.002445 0.021508 ± 0.000888 0.02295 0.000666 0.005799* 0.048636* Tooth quality OTC 0.032053 ± 0.007332 N/D 0.051742 ±0.00882 N/D 0.0000053* Cl〇2 0.03998 ± 0.005542 0.03775 ± 0.00466 0.044608 Soil 0.00392 0.296884 0.027545* N/D=Not determined. * The statistically significant average surface roughness Ra of the chain enamel was about 0.025 before treatment with the non-cytotoxic ceria composition and 0.021 after 2.5 hours of treatment, and about 0.023 after 7 hours of treatment. Therefore, the inverse effect of the gel containing C102 on the average surface roughness of the tannin was not detected, even regardless of the duration of long-term exposure. In fact, in this experiment, after treatment for 2.5 hours with a gel containing C102, the average surface roughness of the tannin was virtually smoother by about 13-14%, indicating an unexpected accident in the absence of abrasive. Tantalum polishing effect. Furthermore, the effect on the average surface roughness of the tooth after 2.5 hours of treatment was not statistically significant. After 7 hours of treatment, the average tooth surface roughness increased by only about 8°/. . As previously mentioned, the 7 hour treatment exceeded the time required for this composition to achieve tooth whitening comparable to OTC or professional peroxide based products (see Examples 5 and 6). Thus, the non-cytotoxic chlorine dioxide composition produces a whitening of teeth equivalent to OTC or specialty products without substantial damage to the enamel or coarse greenness of the dentate surface. In contrast, after the recommended 7-hour contact time, the OTC product 141702.doc -57-201113042 Wang Ai CL. _ ratio-, shows that the surface roughness of the enamel increases by more than about 29 〇 / 0. 7 hours: The tooth surface roughness increased by more than 6〇%. Handling only hrs ^ The professional peroxide product with 36/° hydrogen peroxide increases the surface roughness of both tannins and dents by approximately 203%. Regarding the effect on the bead enamel, very little surface morphology was observed in the non-cytotoxic gel containing c〇2 for 7 hours (Fig. 3B) compared to the untreated control teeth (Fig. 3a). Signs of change. In fact, fine processing to the mark (the result of tooth sample preparation) is still evident. In contrast, a sample treated with a 36% peroxide gel for one hour (Fig. 3c) showed a considerable area of enamel change and possibly corrosion. As shown in Figure 4A, the dentate surface morphology of the control (untreated) teeth has some of the dentate tubules exposed or shown, and the other dentate tubules are covered by a smear layer. Some smear plugs (81^^ plug) are clearly inside the exposed tubules. Contains ίο/ compared to the untreated control dentate surface. The surface of a representative sample of the H2® 2 OTC product treatment (Fig. 4B) shows a larger number of exposed dentinal tubules. The exposed tubules appear to be somewhat enlarged compared to the control surface, and many tubules appear open in the absence of a closed applicator plug. Representative tooth samples treated with a non-cytotoxic gel containing Cl〇2 (Fig. 4C) had a greater number of dentition tubules exposed or displayed compared to the control surface; however, the sample was treated with 〇TC Compared with the small tube, the number is smaller and the size is smaller. The exposed tubules are in the form of narrower "slits" with limited openings; some of the dentinal tubules are covered by a clear smear; some of the smear plugs are clearly within the exposed tubules. Therefore, the surface of the tooth treated with a non-cytotoxic gel containing Cl〇2 is further connected to H1702.doc -58- 201113042. Similar to the surface of the control tooth, although it is not desired to be bound by theory, but salty (tetra) (iv) hydrogen peroxide gel The changes in the tooth surface that are induced, and thus expected to be seen in higher concentration specialty products, may at least partially form the basis of common dental sensitivity problems in commercial products and specialty peroxide whitening products. Experimental Example 9: Clinical Trial The purpose of this human individual feasibility study was to evaluate the edge of the chair, the hour (4) independent 15 minutes of treatment, and the application within the clinic contained about 4. The efficacy of a non-cytotoxic tooth whitening composition of ppm dioxide and high viscosity (tetra)methylcellulose as a phaseing agent component. The composition comprises no more than about 〇 2 oxy-gas anion per gram of composition. Tonal variations and tooth sensitivity to tooth whiteners and patient response to treatment were assessed. Fifteen individuals participated in the clinical trial. In this exploratory, one-arm, uncontrolled, prospective, case-control study, the individual received a textual tooth whitening agent for 1 hour (4 independent! 5 minutes treatment), treatment within the clinic. All individuals were monitored at baseline, immediately after administration in the clinic, 72 hours after administration, and one week after administration within the clinic. Trained inspectors use vha (vita Zahnfabrik) colorimetric plates and color transparency to monitor color changes. The color plate is an acceptable method of evaluation included in the ADA guidelines. The transparency is used as a color after the recording. Tooth sensitivity was monitored at baseline, immediately after treatment in the clinic, «72 hours after treatment in the clinic, and one week after treatment within the clinic. The individual is selected based on the superior anterior teeth with Vita tones of A3 or darker, as judged by comparison with a value-oriented Vita colorimetric plate. Individuals must be 141702.doc •59· 201113042 must be 18-65 years old with good general health and good dental care and oral hygiene. Patients with ongoing dental caries, periodontal disease, large anterior crown or repair, previously bleached or tetracycline-contaminated teeth were not included in the study. After participating in the study, each patient was examined by a clinician. The baseline Vita hue was determined by two evaluators; the uniform tones of the six tested maxillary anterior teeth and the six control mandibular teeth were recorded by the dentist. Digital color transparency (Ph〇tomed si Pro digital camera _Fuji Body; Sigma Lens; Nikon Flash) was prepared at a magnification of 1:丨. The corresponding viu color bar (3}ι_tab) is included in the photo. An alginate impression of the maxillary arch was made and injected into dental hard plaster. Use the materials and designs recommended by the manufacturer to create a custom whitening tray for each patient. All individuals received prophylaxis and were asked to label the standardization scale to assess baseline sensitivity before starting treatment. Clinical trials have begun and preliminary data have been obtained. The disclosures of each of the patents, patents, and publications cited in the Applicables are hereby incorporated by reference in their entirety. Although the compositions, kits, and methods of use thereof have been disclosed with reference to specific embodiments, it will be apparent to those skilled in the art that other embodiments can be devised without departing from the true spirit and scope of the compositions, kits, and methods of use. Examples and changes. It is intended that the scope of the appended claims be interpreted as including all such embodiments and equivalents. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a diagram showing the tooth whitening data of a non-cytotoxic composition containing cl〇2 and a commercially available (OTC) product having muscle 141702.doc 201113042 hydrogen peroxide and total treatment time. Histogram. Cio2 = data for a non-cytotoxic composition containing C102. 〇TC=data for commercial products with 10% hydrogen peroxide; Figure 2 is a diagram showing the non-cytotoxic C102-containing composition compared to a professional whitening gel containing 36% hydrogen peroxide as a bleaching agent. Figure 3A-3C is a series of representative scanning electron microscopy (SEM) microphotograph photomicrography images of the enamel surface at 2500X magnification. Figure 3A shows the enamel of untreated teeth. Figure 3B shows the surface of the enamel after treatment with a non-cytotoxic C102 containing composition. Figure 3C is the enamel surface after treatment with a professional whitening gel containing 36% hydrogen peroxide; and Figures 4A-4C are representative SEM photomicrographs of a series of dent surface at 5000x magnification. Figure 4A shows the dentin of an untreated tooth. Figure 4B shows the dentonic surface after treatment with an OTC whitening gel containing 10% hydrogen peroxide. Figure 4C is the dentonic surface after treatment with a non-cytotoxic C102 containing composition. 141702.doc •61 -

Claims (1)

201113042 七、申請專利範圍: 丄.一種^牙齒表面之方法,該方法包括使該牙録面與 有效里之包含非研磨性拋光劑之拋光組合物接觸,其中 該非研磨性拋光劑包含二氧化氯。 2. 如請求们之方法,其中該組合物為實質上非細跑毒 性。 3. 如凊求項1之方法,其中該拋光組合物包含約5至約丨_ PPm二氧化氣。 4. 如π求項2之方法,其中該拋光組合物包含少於約〇 2毫 克氧-氣陰離子/公克組合物。 月托項1之方法,其中該拋光組合物具有約4.5至約11 之pH值。 求項1之方法,其中該拋光組合物為包含稠化劑組 份之稠化流體組合物。 7. 如請求項6之方法,其中該稠化劑組份係選自由天然水 膠體、半合成水膠體、合成水膠體及黏土組成之群。 8. 如叫求項丨之方法,其中使該牙齒與該組合物接觸會 降低該牙齒表面之表面粗糙度。 9. 如請求項8之方法,其中該表面粗糙度比該牙齒表面與 °玄拋光組合物接觸之前之表面粗糙度降低至少約5〇/〇。 10. 如叫求項丨之方法,其中該牙齒與該組合物接觸時不 會貫質損傷牙齒硬組織。 11. 如叫求項10之方法,其中該牙齒與該組合物接觸時,不 會實質降低琺瑯質顯微硬度。 14I702.doc 201113042 12如明求項丨〇之方法,其中該牙齒與該組合物接觸時不 會實質降低齒質顯微硬度。 13·如請求項12之方法,其中該牙齒與該組合物接觸時,不 會導致牙齒敏感性。 14.如請求項丨之方法,其中該組合物為實質上非刺激性。 15·如請求項!之方法,其中接觸該牙齒表面之步驟引起該 組合物與口腔軟組織之實質性接觸。 16·如請求項丨之方法,其中該組合物為漱口水。 17. 18. 如請求項1之方法,其中不需要保護齒齦。 一種製備牙齒拋光組合物之套組,該套組包含:第一施 配态’其包含二氧化氣之微粒前驅體;第二施配器,其 包含在水性介質中之稠化劑組份;及指示製備包:牙齒 拋光有效量之二氧化氣之實質上非細胞毒性組合物的說 19.如請求項18之套組,其中該第 中之至少一者為注射器。 施配器及該第二施配器 2 0 ·如请求項1 8之套組, 膠體、半合成水膠體 其中該稠化劑組份係選自由天然水 、合成水膠體及黏土組成之群。 141702.doc201113042 VII. Scope of Application: 方法 A method of controlling the surface of a tooth, the method comprising contacting the dent surface with an effective polishing composition comprising a non-abrasive polishing agent, wherein the non-abrasive polishing agent comprises chlorine dioxide . 2. The method of claimant, wherein the composition is substantially non-smooth. 3. The method of claim 1, wherein the polishing composition comprises from about 5 to about 丨 PPm dioxide. 4. The method of claim 2, wherein the polishing composition comprises less than about 2 milligrams of oxygen-gas anion per gram of composition. The method of item 1, wherein the polishing composition has a pH of from about 4.5 to about 11. The method of claim 1, wherein the polishing composition is a thickened fluid composition comprising a thickener component. 7. The method of claim 6, wherein the thickener component is selected from the group consisting of natural hydrocolloids, semi-synthetic hydrocolloids, synthetic hydrocolloids, and clay. 8. The method of claim </ RTI> wherein contacting the tooth with the composition reduces surface roughness of the tooth surface. 9. The method of claim 8, wherein the surface roughness is reduced by at least about 5 〇/〇 prior to contact of the tooth surface with the koji polishing composition. 10. The method of claim </ RTI> wherein the tooth does not mechanically damage the hard tissue of the tooth upon contact with the composition. 11. The method of claim 10, wherein the tooth does not substantially reduce the microhardness of the enamel when contacted with the composition. 14I702.doc 201113042 12 The method of claim 1, wherein the tooth does not substantially reduce the microhardness of the tooth when contacted with the composition. 13. The method of claim 12, wherein the tooth does not cause tooth sensitivity when contacted with the composition. 14. The method of claim 1, wherein the composition is substantially non-irritating. 15·If requested! The method wherein contacting the surface of the tooth causes substantial contact of the composition with the soft tissue of the mouth. 16. The method of claim 1, wherein the composition is a mouthwash. 17. 18. The method of claim 1 wherein there is no need to protect the gums. A kit for preparing a dental polishing composition, the kit comprising: a first dosing state comprising a particulate precursor comprising a dioxide gas; and a second dispenser comprising a thickener component in an aqueous medium; Indicating a preparation package: a substantially non-cytotoxic composition of a tooth-polished effective amount of a oxidizing gas. The kit of claim 18, wherein at least one of the plurality is a syringe. The dispenser and the second dispenser 2 0. The kit of claim 18, colloidal, semi-synthetic hydrocolloid wherein the thickener component is selected from the group consisting of natural water, synthetic hydrocolloids, and clay. 141702.doc
TW98123960A 2008-07-14 2009-07-15 Tooth polishing compositions and methods of tooth polishing without mechanical abrasion TW201113042A (en)

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