TWI513471B - 口腔保健組成物 - Google Patents
口腔保健組成物 Download PDFInfo
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- TWI513471B TWI513471B TW100110884A TW100110884A TWI513471B TW I513471 B TWI513471 B TW I513471B TW 100110884 A TW100110884 A TW 100110884A TW 100110884 A TW100110884 A TW 100110884A TW I513471 B TWI513471 B TW I513471B
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- care composition
- health care
- metal oxide
- cerium oxide
- composition
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- 239000000203 mixture Substances 0.000 title claims description 171
- 239000002245 particle Substances 0.000 claims description 154
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- 229910000420 cerium oxide Inorganic materials 0.000 claims description 67
- BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 claims description 67
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Description
本發明係關於一種口腔保健組成物,例:牙劑組成物,以治療或預防牙齒的過敏性,及關於治療或預防牙齒的過敏性之方法。本發明經由阻塞齒質小管特別應用於治療或預防牙齒的過敏性。
齒質係琺瑯質及齒堊質內的牙齒部分,其由於大量被稱為齒質小管(dentinal tubules)的細管或小管而具有放射條紋外觀,小管由牙髓腔延伸至齒質外圍,且於其基部一般直徑約2微米,而於其外圍稍窄。由於它們通常被琺瑯質或齒堊質包覆,小管通常不暴露於口腔環境中。齒里質從而往往被齒齦包覆。
一般認為部分或完全暴露的小管可導致牙齒敏感(刺激及疼痛的狀況)。於此理論中,齒齦線消退使齒堊質遭受侵蝕。被侵蝕之齒堊質從而暴露出中空齒質小管。因為牙齒內外部的物質及能量傳輸經由該小管被加速,暴露的小管造成牙齒內部神經過度被外部口腔刺激影響。常見環境刺激,如:熱、冷、化學物,及物理與機械性壓力或刺激,如:刷牙,可經由開放的齒質小管刺激神經,並因此產生疼痛,敏感性牙齒的疼痛似乎歸因於這些刺激,其明顯造成齒質小管內液體流動,而觸發牙髓末梢神經。
傳統上採用兩種方式治療或改善牙齒敏感。於一方式中,經由施用各種藥劑改變神經近端化學環境,致使該神經不受刺激或受刺激不大。此化學方式已知有效之藥劑包括鉀鹽(如:硝酸鉀、碳酸氫鉀、氯化鉀),及鍶、鋅鹽、氯化鹽。
第二種方式涉及機械性保護神經,例如:以“小管阻斷劑”完全或部分阻斷齒質小管。先前技術中已揭示之藥劑包括,例如:陽離子氧化鋁、黏土、水溶性或水膨脹性聚電解質、草酸鹽、非結晶型磷酸鈣、羥磷石灰、順丁烯二酸共聚物,及聚乙烯粒子。
以本申請人名義之US-A1-2009/0186090揭示口腔保健組成物的提供,其降低及/或消除牙齒敏感的感受,該組成物包括黏著(adherent)材料,且一部分包括具有2-5微米粒徑的二氧化矽粒子。
然而,即使此一口腔保健組成物提供臨床緩解過敏性,該領域仍需要一種口腔保健組成物,特別是一種牙劑,其經使用而提供增強防護或降低牙齒敏感,且無重大加工或配製缺點。
此發明目的為提供一種口腔保健組成物,特別是一種牙劑,其經使用而提供增強防護或降低牙齒敏感。
本發明因此提供一種口腔保健組成物,其包含口腔可接受載體、具有平均粒徑不大於齒質小管之金屬氧化物粒子,及用於黏附該金屬氧化物粒子於齒質小管中之聚合物黏著材料。
該金屬氧化物粒子可具有5微米或更低之中值粒徑(median particle size)。
該金屬氧化物通常包含至少一種金屬氧化物,其選自氧化鋅、一氧化錫、氧化鈦、氧化鈣、氧化銅及氧化鐵,或其混合物。
該金屬氧化物較佳包含氧化鋅。
該金屬氧化物粒子可具有3至4微米的粒徑分布、5至7微米的粒徑分布、3至5微米的粒徑分布、2至5微米的粒徑分布、或2至4微米的粒徑分布。
該金屬氧化物粒子可以高達5%重量比之量存在,其以該口腔保健組成物之總重為基準,例:0.5至2%重量比之量,其以該口腔保健組成物之總重為基準。
該金屬氧化物可以至少一種形式被納入該口腔保健組成物中,該形式係選自粉末、奈米粒子溶液或懸浮液,或被封裝於聚合物或珠粒中。
一般而言,該金屬氧化物被封裝於聚合物黏著材料中。於某些具體實例中,該聚合物黏著材料包含至少一種纖維素聚合物。
該至少一種之纖維素聚合物可為一或多種羥烷基纖維素聚合物,其選自:羥丙基甲基纖維素(HPMC)、羥乙基丙基纖維素(HEPC)、羥丁基甲基纖維素(HBMC),及羧甲基纖維素(CMC)。
一般而言,該聚合物黏著材料包含具不同分子量的兩種羥烷基纖維素聚合物之混合物,且該金屬氧化物包含氧化鋅,其被封裝於該兩種羥烷基纖維素聚合物之混合物中。
於其他具體實例中,聚合物黏著材料包含至少一種聚合物,其選自包括:聚(環氧乙烷)聚合物、線狀聚乙烯吡咯啶酮(PVP)及經交聯之聚乙烯吡咯啶酮(PVP)、聚乙二醇(PEG)/聚丙二醇(PPG)共聚物、環氧乙烷(EO)-環氧丙烷(PO)嵌段共聚物、酯膠、蟲膠、感壓性聚矽氧黏著劑、甲基丙烯酸酯或其混合物。
口腔保健組成物較佳進一步包含二氧化矽粒子,其具有不大於齒質小管的平均粒徑。
一般而言,二氧化矽粒子具有8微米或更低之中值粒徑,例:2至5微米。
二氧化矽粒子可以高達10%重量比,例:3至6%重量比之量存在,其以該口腔保健組成物之總重為基準。
該口腔保健組成物較佳係牙劑組成物,如:牙膏或凝膠。
此外,該口腔保健組成物被配製成一形式,其選自漱口水、膠、可溶性錠劑及可溶性薄片。
本發明進一步提供一種降低牙齒敏感性的方法,其包含施用本發明之口腔保健組成物至哺乳動物牙齒表面。
本發明更進一步提供一種保護牙齒表面免於經酸媒介降解(acid-mediated degradation)的方法,其包含施用本發明之口腔保健組成物至哺乳動物牙齒表面。
本發明仍進一步提供一種維持或增進哺乳動物全身健康的方法,其包含於一段時間每日至少一次施用組成物至哺乳動物口腔表面,其中該組成物包含:
a. 本發明之口腔保健組成物,及
b. 藥劑,其選自:三氯沙、三氯沙單磷酸鹽、氯已定(chlorhexidine)、阿來西定(alexidine)、海克西定(hexetidine)、血根鹼、氯化苄烷銨(benzalkonium chloride)、柳醯胺苯、溴化度米芬(domiphen bromide)、氯化鯨蠟吡啶(cetylpyridinium chloride,CPC)、氯化十四基吡啶(tetradecylpyridinium chloride,TPC)、氯化N-十四基-4乙基吡啶(TDEPC)、奧替尼啶(octenidine)、地莫匹醇(delmopinol)、辛哌醇(octapinol)、乳酸鏈球菌素、鋅離子劑、銅離子劑、精油、呋喃酮、細菌素、月桂醯精胺酸乙酯(ethyllauroyl arginate)、木蘭萃取物、金屬離子源、氟化物、亞錫離子、碳酸氫精胺酸、異厚朴醇(honokiol)、厚朴醇(magonol)、熊果酸、植酸(ursic acid)、桑色素、沙棘萃取物、過氧化物、酶、山茶(Camellia)萃取物、類黃酮、黃烷、鹵化二苯基醚、奎瑞替夫(creative),及蜂膠。
本發明亦提供一種阻塞哺乳動物牙齒表面內齒質小管之方法,其包含施用依據本發明的組成物至牙齒表面。
該組成物可含有附加治療性及非治療性成分,且可亦被應用於各種方法之施行,以上所有皆囊括於本發明範疇中,於本發明範疇之該組成物及方法可能有益於,例如:降低或消除哺乳動物之牙齒敏感、增進/維持全身健康,及/或阻塞齒質小管。
本發明係基於本發明人之發現,當該金屬氧化物粒子與黏著性聚合物一起使用時,治療有效量之特定粒徑的金屬氧化物粒子可輕易阻塞齒質小管。此外,當大致與該金屬氧化物粒子粒徑相當的二氧化矽粒子與該金屬氧化物粒子結合,甚至可達到更大齒質阻塞,尤其是當牙齒表面接觸酸性環境時。再更進一步,該金屬氧化物粒子可被選用於對口腔提供附加治療性益處,例:當該金屬氧化物含有氧化鋅的抗牙菌斑/抗結石效果。
當表明本發明之具體實例時,應瞭解詳述及特定實例係僅用於說明的目的,而非意圖限制本發明之範疇。
以下僅定義及非限制性準則必須被視為檢閱此後本發明之敘述。於此使用之標題(如:“發明背景”及“摘述”)及次標題(如:“組成物”)意為僅供概括組織本發明揭示內容內之細目,而非意圖限制本發明揭示內容之範疇或其任何方面。特別是於“發明背景”揭示之標的可包括本發明範疇內的技術方面,且可不構成先前技術之詳述。揭示於“摘述”之標的非本發明整個範疇的詳盡或完全揭示內容或其任何具體實例。於此說明書章節內之材料的分布或論述(例:作為一個“活性”或一個“載體”成分)係為了方便,而非推論當其使用於任何給定之組成物時,該材料必然或完全與此處之分布作用。
此處引用之參考文獻未構成承認那些參考文獻為先前技術,或具有於此之發明可專利性有關。於本發明背景中引用之參考文獻內容的任何論述完全是為了提供該參考文獻作者主張之概括摘述,而未構成承認此參考文獻內容之正確性。因此於此引用之各個及所有參考文獻藉此將其全文納入做為參考。
當表明本發明之具體實例時,敘述及特定實例僅為了說明的目的,而非意圖限制本發明之範疇。再者,具指定特點之多重具體實例的詳述非意圖排除具附加特點之其他具體實例,或結合不同組合之指定特點的其他具體實例。提供特定實例之目的是說明如何製造及使用本發明之組成物及方法,且除非另有明確說明,非意圖表示本發明給定之具體實例已經或未經製造或測試。
當於此使用時,字“優先的”和“較佳的”係指在某些情況下給予必然利益的本發明具體實例,然而,在相同或其他情況下,其他具體實例亦可能為優先的,再者,一個或多個較佳的具體實例之敘述並不意味著其他具體實例為無用的,而非為了由本發明範疇排除其他具體實例。此外,組成物和方法可包括實質上由或由此處所述的要素所構成。
當於此使用時,字“包括”及其變體的意圖為非限制性,因此列表中項目的敘述並非要排除亦可用於此發明的材料、組成物、設備及方法的其他類似項目。
當於此使用時,詞語“約”應用到本發明組成物或方法之參數值時,意指該計算或測量值允許一些輕微的不精確度,而不對該組成物或方法之化學或物理屬性造成重大影響。若因某些原因,由“約”造成之不精確度與本領域常義無歧異,則當於此使用時,“約”意指數值上高達5%之可能變異。
除非另有規定,於此引用之所有成分百分比係該總組分之重量百分比。
此處所述本發明包括一種口腔保健組成物,其含有至少(a)聚合物黏著材料,及(b)金屬氧化物粒子。金屬氧化物粒子可具有不大於齒質小管之平均粒徑,或其可具有5微米或更低之中值粒徑。金屬氧化物粒子可以高達5%重量比,較佳是高達2%重量比,更好是由0.5至2%重量比,更佳是由1至2%重量比之量存在,其以口腔保健組成物之總重為基準。
金屬氧化物可包括一或多種金屬氧化物,其選自氧化鋅、一氧化錫、氧化鈦、氧化鈣、氧化銅及氧化鐵。可使用此金屬氧化物之混合物。然而,最優先考慮氧化鋅。氧化鋅係本領域熟知當使用於口腔保健組成物中作為抗牙菌斑及抗結石劑。因此,當氧化鋅使用於本發明較佳具體實例之口腔保健組成物時,氧化鋅可展現雙重功能,即阻塞齒質小管和提供抗牙菌斑/抗結石效果。
金屬氧化物可以一或多種形式被納入口腔保健組成物中,例如:以粉末,以奈米粒子溶液或懸浮液,例如:於水中,或封裝於聚合物或珠粒。
依據本發明特定具體實例,口腔保健組成物額外包含(c)二氧化矽粒子。二氧化矽粒子可具有不大於齒質小管之平均粒徑,或其可具有8微米或更低之平均粒徑。粒子可以高達10%重量比,較佳由1至7.5%重量分比,更好由3至6%重量百分比,更較佳約5%重量比之量存在,該重量以口腔保健組成物之總重為基準。
因此,本發明具體實例包括金屬氧化物,較佳為特定粒徑之氧化鋅粒子,且較佳亦為特定粒徑之二氧化矽粒子,該粒徑於每一情況中被選為達成齒質粒子的阻塞。
在本說明書中,使用馬爾文(Malvern)粒徑分析儀,型號Mastersizer 2000(或同等型號)(馬爾文儀器公司,Southborough,Mass)測量粒徑分布,其中氦氖氣體雷射光束通過一個透明管,其含有二氧化矽,諸如例如:懸浮於水溶液之二氧化矽凝膠粒子。擊中粒子的光線以對粒徑成反比之角度散射。該光探測器於一些預定的角度測量光量。與測量光通量值成比例的電子信號之後由微電腦系統處理,由該樣本及水性分散劑之折射率限定之理論粒子所預測之散射圖,以測定金屬氧化物或二氧化矽之粒徑分布。未來將瞭解測量粒徑之其他方法為本領域所熟知,並根據於此訂定之揭示內容,技術人士將明白如何計算中值粒徑、平均粒徑,及/或本發明之金屬氧化物及/或二氧化矽粒子的粒徑分布。
於一方面,本發明口腔組成物之適當金屬氧化物粒子,諸如:氧化鋅粒子及視情況二氧化矽粒子,具有例如:3至4微米的粒徑分布,或5至7微米的粒徑分布,或者,3至5微米的粒徑分布,或者,2至5微米的粒徑分布,或2至4微米的粒徑分布。金屬氧化物及二氧化矽粒徑範圍可能相同或不同。
本發明範疇內之口腔組成物包括金屬氧化物粒子,諸如:氧化鋅,視情況額外的二氧化矽粒子,其具有不大於哺乳動物齒質小管平均直徑的中值粒徑,因此一或多個粒子可進入該小管內,從而造成減少或消除所察覺的牙齒敏感。適宜之粒子可具有例如:8微米或更低之中值粒徑,或者,3至4微米之中值粒徑,或者,5至7微米之中值粒徑,或者,3至5微米之中值粒徑,或者,2至5微米之中值粒徑,或者,2至4微米之中值粒徑。
於本發明的一方面,該金屬氧化物粒子,諸如:氧化鋅,及視情況額外的二氧化矽粒子具有粒徑,其為中值粒徑;於另一方面,此粒徑係一平均粒徑(均值(mean))。於一具體實例中,平均粒子包括總金屬氧化物和/或二氧化矽粒子的至少5%,至少10%,至少15%,至少20%,至少25%,至少30%,至少35%,或至少40%於本發明之口腔保健組成物中。
於本發明的一個方面,金屬氧化物粒子,諸如:氧化鋅,及視情況額外的二氧化矽粒子具有粒徑,其特徵為約2微米至約4微米的中值粒徑之參數,約0.5微米至約2微米的d10,及約5到10微米的d90。當於此使用時,d10意指一粒子,其具有10%抽樣族群閾值的直徑(亦即該族群10%等於或小於該d10值),而d90意指粒子,其具有90%抽樣族群閾值的直徑(亦即該族群90%等於或小於該d90值)。另一方面,金屬氧化物,諸如:氧化鋅,以及任何任選的二氧化矽,其具有粒徑,特點為約3微米至5微米的平均粒徑,約1.5至約3微米的d10,及約6微米至約11微米的d90。
於本發明的另一方面,含二氧化矽的牙劑中至少一部分的二氧化矽具有3.95微米的d50(亦即二氧化矽粒子族群50%等於或小於d50值)。特別較佳的二氧化矽為索玻矽AC43(Sorbosil AC43),其可由英國威靈頓的英力士二氧化矽(Ineos Silicas)商業性取得。索玻矽AC43二氧化矽具有3.95微米的d50。經由一非限制性實例,使用本文他處設定的粒徑測量技術(例:MALVERN MASTERSIZER)測量該d50。於一個具體實例中,含二氧化矽的牙劑具有一群處於及低於3.95微米的粒子,其由粒徑測量所獲得的曲線下面積(AUC)測定。當於此使用時,術語“AUC3095”意指粒子<=3.95微米之粒子的累計體積分數。經由一個非限制性實例,具有20%其粒子<=3.95微米的組成物據稱具有20%的累積粒徑體積分數(AUC3095)。
於一個具體實例中,本發明的含二氧化矽之牙劑具有AUC 3.95值至少18%,進一步任意至少22%、24%、26%、30%、40%、42%、45%,或50%。
於本發明的一個方面,二氧化矽粒子於600埃或更低的孔洞中具有小於約0.45立方厘米/克的孔隙率。
於一個具體實例中,二氧化矽為英力士(INEOS)(現在的PQ公司)索玻矽AC43二氧化矽。於一個具體實例中,AC43二氧化矽具有的性質,包括但不限於,2.7-4.0微米的平均粒徑(如同MALVERN MASTERSIZER所測定),+45微米的篩殘餘物(sieve residue),於105℃時水分損失最大8.0%,於1000℃時燒失量最大14.0%,而於水性懸浮液中酸鹼值5.5-7.5。
於一個具體實例中,金屬氧化物及/或二氧化矽粒子可最初存在於具有所需粒徑之組成物中,或可最初存在於較大尺寸的組成物中,只要該粒子的結構經施加機械力,如:刷牙時的牙刷,而其斷裂或碎裂成所需的粒徑。或者是,二氧化矽起始原料係小粒子二氧化矽。
可經由任何已知或將於該領域開發的方法製備該金屬氧化物及/或二氧化矽粒子,且若需要的話,並可能被表面修飾,以增加粒子的吸收力而附著於牙齒表面。可於例如:US-A1-2007/0104660找到實例,其內容已納入本文作為參考。
除金屬氧化物及任選二氧化矽齒質小管-阻塞粒子之外,口腔組成物可進一步包括一或多種磨料微粒,可使用任何磨料微粒,並可選自:碳酸氫鈉、磷酸鈣(例:二水合磷酸二鈣)、硫酸鈣、沉澱碳酸鈣、二氧化矽(例如:水合二氧化矽)、氧化鐵、氧化鋁、珍珠岩、塑膠粒子,例:聚乙烯,及其組合物。特別是,磨料可選自磷酸鈣(例:二水合磷酸二鈣)、硫酸鈣、沉澱碳酸鈣、二氧化矽(例:水合二氧化矽)、焦磷酸鈣及組合物。可使用任何類型的二氧化矽,諸如沉澱二氧化矽或二氧化矽凝膠。
於一個具體實例中,口腔保健組成物包括二氧化矽,其具有粒徑和數量,並分佈於口腔保健組成物中,使得該二氧化矽具有雙重功能,且功能不僅作為齒質小管-阻塞微粒,並且亦作為磨料微粒。如此雙重功能可由市售二氧化矽提供,諸如英力士(INEOS)AC43,如本文其他處所述可由英國威靈頓英力士(Ineos silica)二氧化矽商業性獲得。於一具體實例中,此二氧化矽如本文其他處細節所述具有自3微米至5微米的中值粒徑。
依據本發明可使用各種磨料。一類磨料如本文詳細闡述含有二氧化矽粒子。另一種磨料係粉末狀二氧化矽,尤其是定義於US-B-3,538,230之二氧化矽乾凝膠,此外,如同說明於US-B-4358437,於磨料形式之粉末狀碳酸鈣係另一類磨料。
本發明之組成物可進一步包含有益於例如:作為拋光劑之任選磨料。可使用任何口腔可接受之磨料,但應選擇磨料之類型、細度、(粒徑)及數量,使牙齒琺瑯質於正常使用該組成物時不致過度磨損。適宜之任選磨料包括二氧化矽,例如:沉澱二氧化矽之形式,或摻合氧化鋁、不溶性磷酸鹽、碳酸鈣及其混合物。有用於做為磨料之不溶性磷酸鹽係正磷酸鹽、聚偏磷酸鹽及焦磷酸鹽。說明之實例為二水合正磷酸二鈣、焦磷酸鈣、焦磷酸鈣、磷酸三鈣、聚偏磷酸鈣及不溶性聚偏磷酸鈉。
本發明之口腔組成物亦包括聚合物黏著材料。聚合物於唾液流動及接觸到酸性食物和飲料時,幫助保留該金屬氧化物粒子及二氧化矽粒子(當存在時)於齒質小管內。
聚合物黏著材料可為本領域任何已知或待開發之材料,其附著至哺乳動物牙齒表面,及/或至亦可存在於牙齒表面之異種生物膜。可以任何方式產生附著作用,諸如:離子交互作用、凡得瓦力、疏水性-親水性交互作用...等。黏著材料可為,例如:任何同元聚合物或共聚物(以下統稱為“聚合物”),其黏附至牙齒表面。此聚合物可包括纖維素聚合物,例如:一或多種羥烷基纖維素聚合物,諸如:羥丙基甲基纖維素(HPMC)、羥乙基丙基纖維素(HEPC)、羥丁基甲基纖維素(HBMC)、羧甲基纖維素(CMC)。
於一具體實例中,聚合物黏著材料含有纖維素材料之混合物,例如:具有不同分子量的兩個羥烷基纖維素原料之混合物。該混合物通常含有不同分子量的兩個羥丙基甲基纖維素材料之混合物。於一特別較佳具體實例中,該兩個羥丙基甲基纖維素材料含有羥丙基甲基纖維素材料之混合物,可由陶氏化學公司(Dow Chemical Company)購得,商品名為美多秀E5(Methocel E5)及美多秀E50(Methocel E50)。
聚合物可隨意或額外包含聚(環氧乙烷)聚合物(諸如:來自陶氏化學的保益樂(POLYOX))、線狀PVP及經交聯之PVP、PEG/PPG共聚物(諸如:巴斯夫公司(BASF)的布魯雷卡L1220(Pluracare L1220))、環氧乙烷(EO)-環氧丙烷(PO)嵌段共聚物(諸如:巴斯夫公司售出之商品名為布魯若尼可(Pluronic)的聚合物)、酯膠、蟲膠、感壓性聚矽氧黏著劑(諸如:陶氏-康寧公司(Dow-Corning)之BioPSA)、甲基丙烯酸酯或其混合物。於一具體實例中,共聚物含有(PVM/MA)。於一具體實例中,共聚物含有聚(甲基乙烯基醚/順丁烯二酐)。於另一具體實例中,共聚物含有聚(甲基乙烯基醚/順丁烯二酸)。在另一具體實例中,共聚物含有聚(甲基乙烯基醚/順丁烯二酸)半酯。於另一具體實例中,共聚物含有聚(甲基乙烯基醚/順丁烯二酸)混合鹽。
可使用任何分子量之聚合物,包括例如:分子量為50,000至500,000,500,000至2,500,000或2,500,000到10,000,000(由數量平均或重量平均計算)。
於一具體實例中,可使用單體比例由1:4至4:1的甲基乙烯基醚及順丁烯二酐之共聚物。可作為黏著材料的其他聚合物包括那些列舉於US-A1-2006/0024246者,該內容納入本文作為參考。
市售之聚合物可用於本發明。據了解,隨著時間的推移,市售聚合物之確切尺寸、重量及/或組成可能發生變化。依據本文揭示內容,本發明所屬技術領域中具有通常知識者將明瞭如何確定是否該聚合物可用於本發明。
於本發明之一方面,含金屬氧化物粒子之口腔保健組成物(其可視情況含有二氧化矽粒子)可降低牙齒敏感。於另一方面,本發明之該組成物提供牙齒減敏作用,其優於傳統減敏牙劑。於一個非限定實例中,本發明之含金屬氧化物粒子的牙劑經由提供較傳統牙劑或習用減敏牙劑更佳減敏作用,經由提供較傳統牙劑或習用減敏牙劑更快速減敏作用,或經由結合其他作用中更佳減敏作用及更快速減敏作用,而提供牙齒減敏作用。於一具體實例中,本發明的含金屬氧化物粒子之組成物於沒有任何其他減敏劑的情況下,提供減敏作用及/或更佳減敏作用。於另一具體實例中,本發明的含金屬氧化物粒子之組成物提供減敏作用及/或更佳減敏作用,並可包含一或多種額外減敏劑,諸如:本文他處所述之二氧化矽粒子。
本發明亦囊括含金屬氧化物粒子之減敏組成物的使用方法及/或應用,該組成物可視情況含有二氧化矽粒子。於一具體實例中,此含金屬氧化物粒子之組成物可經由習知刷牙方式塗敷於牙齒(例:使用牙刷)。於另一具體實例中,此含金屬氧化物粒子之組成物經由習知刷牙方式以外的方法塗敷於牙齒,其他塗敷方法包括:徒手塗敷(例:使用一或多隻手指塗敷組成物至牙齒,塗擦至牙齒表面,摩擦圓周運動...等),或使用任何已知牙科設備或設施塗敷。依據本文說明,將瞭解塗抹組成物至牙齒,視情況使用不同程度之物理性壓力的任何方法皆囊括於本發明中。
可經由本文說明之任何技術,或本發明所屬技術領域中具有通常知識者已知之任何技術測量依據本發明之牙齒減敏作用。
塗敷該組成物於牙齒表面,導致引進該組成物進入一或多個齒質小管,該組成物經由本文說明或該領域已知之任何方法塗敷至牙齒。
口腔保健組成物可包括任何其他治療的、化妝用的及/或可能所需之美容材料。例子包括:非二氧化矽減敏劑(例:硝酸鹽、精胺酸酯、碳酸氫鹽、硝酸鉀、精胺酸-碳酸氫鹽-植酸鹽複合物、檸檬酸鉀及精胺酸,等等),化學美白劑(諸如:過氧化物釋放化合物),不透明美白劑(諸如:羥磷石灰)和抗結石劑。列入本發明之口腔保健組成物的其他選項包括:三氯沙、亞錫離子劑、氯己定、阿來西定、海克西定、血根鹼、氯化芐烷銨、柳醯胺苯、溴化度米芬、氯化鯨蠟吡啶(CPC)、氯化鯨蠟吡啶氯化十四基吡啶(TPC)、氯化N-十四基-4乙基吡啶(TDEPC)、奧替尼啶、地莫匹醇、辛哌醇、乳酸鏈球菌素、鋅離子劑、銅離子劑、精油、呋喃酮、細菌素、月桂醯精胺酸乙酯、木蘭萃取物、金屬離子源、碳酸氫精胺酸、異厚朴醇、厚朴醇、熊果酸、植酸、桑色素、沙棘萃取物、酶、山茶萃取物、類黃酮、黃烷、鹵化二苯基醚、肌酸及蜂膠。
口腔保健組成物可能特別為牙劑組成物,其可為牙膏或凝膠。
依據本發明之組成物可包含抗微生物劑,其可選自:鹵化二苯基醚(三氯沙)、草藥萃取物或精油(例如:迷迭香萃取物、茴香油、薄荷醇、桉油醇、柳酸甲酯)、雙胍防腐劑(例:氯己定、阿來西定或奧替尼啶)、酚系防腐劑、海克西定、聚維酮碘、地莫匹醇、5-正辛醯-3'-三氟甲基苯基水楊醯胺(salifluor)、血根鹼、蜂膠、充氧劑(例:過氧化氫、緩衝性過氧硼酸鈉或過氧碳酸鈉)、氯化鯨蠟吡啶、木蘭萃取物、厚朴醇、異厚朴醇、丁基厚朴醇、丙基異厚朴醇及其混合物。抗附著劑,諸如:索羅(Solrol)亦可包括在內,以及牙菌斑分散劑,諸如:酶(木瓜酶、葡萄糖澱粉酶...等)。
依據本發明之組成物亦可包含一或多種其他的藥劑,通常選自:抗牙菌斑劑、美白劑、抗菌劑、清洗劑、調味劑、甜味劑、黏著劑、界面活性劑、發泡調節劑、磨料、酸鹼值改良劑、保濕劑、口感劑、著色劑,磨料,牙石控制(抗結石)劑、氟化物離子源、唾液刺激劑、營養及其組合物。可添加至該組成物的各種成分包括,例如:甜味劑,諸如:糖精或糖精鈉,醇類,諸如:乙醇,氟化物離子源,諸如:氟化鈉,以及甘油、山梨糖醇、丙二醇、聚乙二醇、聚合膠(Poloxomer)聚合物,諸如:POLOXOMER 407、PLURONIC F108(兩者皆可由巴斯夫公司購得)、烷基多醣苷(APG)、聚山梨醇酯、聚乙二醇40、蓖麻油、薄荷醇...等。
本文中可用的那些調味劑包括任何可用來提升組成物風味的材料或材料之混合物。可使用任何口腔可接受之天然或合成的調味劑,諸如:調味油、調味醛類、酯類、醇類、類似材料及其組合。調味劑包括:香草、鼠尾草、馬鬱蘭、香芹油、綠薄荷油、肉桂油、冬青油(甲基柳酸酯)、薄荷油、丁香油、月桂油、大茴香油、桉樹油、柑橘油、果油及香精,包括那些來自檸檬、柑橙、萊姆、葡萄柚、杏、香蕉、葡萄、蘋果、草莓、櫻桃、鳳梨...等,豆類及堅果衍生口味,諸如:咖啡、可可、可樂、花生、杏仁...等,吸附和封裝調味劑及其混合物。本文之調味劑亦囊括可於口中提供香味及/或其他感官作用,包括冷卻或升溫作用之成分,這些成分包括薄荷醇、乙酸薄荷酯、乳酸薄荷酯、樟腦、桉樹油、桉油醇、茴香腦、丁香酚、桂皮、覆盆子酮、[α]-紫羅蘭酮、丙烯基鄰乙氧基苯酚(propenyl guaiethol)、茴香油、沈香醇、苯甲醛、桂皮醛、N-乙基-對-薄荷烷-3-碳沙敏(N-ethyl-p-menthan-3-carboxamine)、N,2,3-三甲基-2-異丙基丁醯胺、3-1-薄荷氧基丙烷-1,2-二醇、肉桂醛甘油縮醛(CGA)、薄荷酮甘油縮醛(MGA)及其混合物。一或多種調味劑視情況以總量約0.01%至約5%,於不同具體實例中,視情況由約0.05%至約2%,由約0.1%至約2.5%,由約0.1%至約0.5%存在。
本文中可用的那些甜味劑包括:右旋糖、聚右旋糖、蔗糖、麥芽糖、糊精、乾轉化糖、甘露糖、木糖、核糖、果糖、左旋糖、半乳糖、玉米糖漿、部分水解澱粉、氫化澱粉水解物、山梨糖醇、甘露醇、木糖醇、麥芽糖醇、異麥芽酮糖醇、阿斯巴甜、紐甜、糖精及其鹽類、蔗糖素、二肽為基礎的高甜度甜味劑、賽克拉美、苯基苯乙基酮(dihydrochalcones)及其混合物。
口感劑包括當使用組成物時,給予所欲質地或其他感受之材料。
本文中可用的那些著色劑包括色料、染料、沉澱染料及給予特定光澤或反射率之藥劑,諸如:珍珠劑,於各種具體實例中,著色劑被用為提供牙齒表面白色或淺色塗層,以作為牙齒表面與該組成物有效接觸位置之指示物,及/或修飾外觀,特別係組成物之顏色及/或不透明度,以加強對對消費者的吸引力。可使用任何口腔可接受之著色劑,包括FD & C染料和色料、滑石、雲母、碳酸鎂、碳酸鈣、矽酸鎂、矽酸鎂鋁、二氧化矽、二氧化鈦、氧化鋅、紅、黃、棕及黑色氧化鐵、亞鐵氰化鐵銨、錳紫、群青、雲母鈦、氧氯化鉍及其混合物。一或多種著色劑視情況可以總量的約0.001%至約20%,例如:約0.01%至約10%,或約0.1%至約5%存在。
本發明之組成物視情況包含牙石控制(抗結石)劑,本文中可用的那些牙石控制劑包括任何這些藥劑之鹽類,例如:它們的鹼金屬及銨鹽:磷酸鹽及聚磷酸鹽(例如:焦磷酸鹽)、聚胺基丙磺酸(AMPS)、聚烯烴磺酸鹽、聚烯烴磷酸鹽、二磷酸鹽類,諸如:氮雜環烷-2,2-二磷酸鹽(例如:吖環庚烷-2,2-二磷酸)、N-甲基吖環戊烷-2,3-二磷酸、乙烷-1-羥基二膦酸(EHDP)及乙烷-1-胺基-1,1-二磷酸鹽類及磷烷羧酸。可用的無機磷酸鹽及聚磷酸鹽包括磷酸二氫鈉、磷酸氫二鈉、磷酸三鈉(monobasic,dibasic and tribasic sodium phosphates)、三聚磷酸鈉、四聚磷酸鹽、單、雙、三及四鈉焦磷酸鹽、三偏磷酸鈉、六偏磷酸鈉及其混合物。
本發明之組成物視情況包括氟化物離子源,並可用於,例如:作為防齲劑。可使用任何口腔可接受之微粒狀氟化物離子源,包括:鉀、鈉、銨的氟化物及單氟磷酸鹽類、二氟化錫、氟化銦、胺氟化物,諸如:奧拉氟(olaflur)(N'-十八基三甲基二胺-N,N,N'-參(2-乙醇)-二氫氟化物)及其混合物。一或多種氟化物離子源係以提供口腔組成物臨床有效量的可溶性氟化物離子之量存在。
本發明之組成物視情況包含唾液刺激劑,可用於,例如:改善口腔乾燥。可使用任何口腔可接受之唾液刺激劑,包括但不限於食品酸,諸如:檸檬酸、乳酸、蘋果酸、琥珀酸、抗壞血酸、己二酸、延胡索酸及酒石酸,及其混合物。一或多種唾液刺激劑視情況以唾液刺激有效總量存在。
本發明之組成物視情況包含營養素。適宜之營養素包括:維生素、礦物質、胺基酸及其混合物。維生素包括維生素C及D、硫胺素、核黃素、泛酸鈣、菸鹼酸、葉酸、菸鹼醯胺、吡哆醇(pyridoxine)、氰鈷銨素(cyanocobalamin)、對胺基苯甲酸、生物類黃酮及其混合物。營養補充品包括:胺基酸(諸如:L-色胺酸、L-離胺酸、甲硫胺酸、絲胺酸、左卡尼汀(levocarnitine)及L-肉鹼),親脂物(諸如:膽鹼、肌醇、甜菜鹼、亞麻油酸)及其混合物。
依據本發明之牙劑組成物於產物,諸如:牙膏或凝膠中包含口腔可接受之載體。當於此使用時,“口腔可接受之載體”係意指材料或材料之組合,其以一相應的合理利益/風險比例,安全地使用於本發明之組成物中。
較佳用於本發明之特定材料及組成物因此係醫藥或美容上可接受的,臨床有效及/或臨床靈驗的。當於此使用時,這樣“醫藥上可接受”或“美容上可接受的”、“臨床有效的”及/或“臨床靈驗的”成分為適合人類及/或動物使用之部份,並提供一適當量(臨床有效量),其以一相應的合理利益/風險比例提供所欲之治療、預防、感官、修飾或美容益處,而無過度不良副作用(諸如:毒性、刺激性及過敏反應)。
本文所述之口腔保健組成物可配製成任何輸送形式,其使得該黏著材料及粒子接觸牙齒表面。例如:組成物可配製成漱口水、糊劑、凝膠、錠劑(可溶性或可咀嚼)、噴劑、膠及薄片(完全或部分可溶性,或不可溶性)。組成物可含有任何習知賦形劑或載體,雖然這些將取決於劑量型式或所選劑量之方式。賦形劑或載體可包括,例如:保濕劑、著色劑、調味劑、甘油、山梨糖醇、木糖醇及/或丙二醇、水或其他溶劑、膠主劑(gum bases)、增稠劑、界面活性劑、卡拉膠(豐富苔蘚)、三仙膠及羧甲基纖維素鈉、澱粉、聚乙烯吡咯啶酮、羥乙基丙基纖維素、羥甲基纖維素、羥丙基甲基纖維素、羥乙基纖維素及非結晶型二氧化矽。
若需要,界面活性劑可包括在內。適宜之界面活性劑的例子包括:高級(higher)脂肪酸單甘油酯單硫酸酯之水溶性鹽,諸如:氫化椰子油脂肪酸的單硫酸酯化單甘油酯鈉鹽;高級烷基硫酸鹽,諸如:十二基硫酸鈉;烷基芳香基磺酸鹽,諸如:十二基苯磺酸鈉;高級烷基磺基乙酸鹽,諸如:十二基磺基乙酸鈉;1,2-二羥基丙烷磺酸鹽的高級脂肪酸酯;以及低級(lower)脂肪族胺基羧酸化合物的實質上飽和高級脂肪族醯基醯胺,諸如:那些在脂肪酸、烷基或醯基具有12-16個碳者...等。最後提及之醯胺的例子包括:N-十二基肌胺酸,及N-十二基、N-十四醯基或N-棕櫚醯肌胺酸的鈉、鉀及乙醇胺鹽。其他包括例如:非陰離子性聚氧乙烯界面活性劑,諸如:聚合膠(Polyoxamer)407、硬脂醇聚醚(Steareth)30、聚山梨酯(Polysorbate)20及蓖麻油;以及兩性界面活性劑,諸如:椰油醯胺丙基甜菜鹼(泰構拜(tegobaine))、椰油醯胺丙基甜菜鹼十二基葡萄糖苷;環氧乙烷與各種與其有反應性且具有長烴鏈(例:12至20個碳原子的脂肪族鏈)的含氫化合物之縮合產物,其中縮合產物(艾縮體(ethoxamers))含有親水性聚氧乙烯基團,諸如:聚(環氧乙烷)與脂肪酸、脂肪、醇、脂肪醯胺及其他脂肪基團,以及與環氧丙烷和聚環氧丙烷的縮合產物。
於一具體實例中,口腔組成物包括界面活性劑系統,其為十二基硫酸鈉(SLS)及椰油醯胺丙基甜菜鹼。
可經由該領域任何已知方式製備本發明之口腔保健組成物。例如:牙劑的製備方法眾所周知,例如:如US-B-3966863、US-B-3980767、US-B-4328205及US-B-4358437所述,其內容已納入本文作為參考。一般而言,任何保濕劑(例:甘油、山梨糖醇、丙二醇及/或聚乙二醇)於習用攪拌器中攪拌後,分散於水中,添加增稠劑至該分散體中,諸如:羧甲基纖維素(CMC)、卡拉膠或三仙膠,任何陰離子聚羧酸鹽,任何鹽類,諸如:氟化鈉防齲劑,以及任何甜味劑。
攪拌產生的混合物,直到形成均勻凝膠相。於凝膠相中添加任何可使用的色料,諸如:二氧化鈦,以及任何調節組成物酸鹼值所需之額外酸或鹼。混合這些成分,直到獲得均勻相。
混合物之後移至高速/真空混合機中,其中加入界面活性劑成分至混合物。依序加入金屬氧化物粒子及任何可使用的二氧化矽粒子。任何不溶於水的藥劑,諸如:三氯沙,溶解在包含於牙劑的調味油中,並與界面活性劑一同將該溶液加入混合物中,之後於真空20至50毫米汞柱下,高速混合5至30分鐘。所得產物為均質半固體,可擠壓之糊劑或凝膠產品。
依據本發明之口腔保健組成物,例如:牙劑,可給予或施用至人類或其他動物個體。組合物適用於給予或施用至人或動物個體之口腔。
本發明於其範圍內亦包括數種相關方法。例如:本發明於其範圍內包括減少的方法,及阻塞哺乳動物牙齒齒質小管的方法,保護齒質免於經酸媒介降解的方法,及降低牙齒敏感性的方法。
這些方法各個包括施用上述任何組成物於牙齒表面之步驟。只要該黏著材料及粒子被置放於可接觸到牙齒表面,可用任何方法進行施用。經由刷洗、使用牙線、預防、沖洗、擦拭、漂洗(灌洗口腔)、泡沫/凝膠及淺盤施用、咀嚼、噴塗、塗抹...等,完成施用,或由薄片或條帶施用。
依據本發明之方法,經由施用本發明組成物至牙齒表面,可降低牙齒敏感性。可使用如同本文它處詳述之傳統方法,或以任何設備或設施施用一組成物,不論其是否通常與牙科使用相關。於一具體實例中,一或多個人手指被用於施用牙齒減敏組成物至一或多個牙齒。手指可被用以塗抹該組成物至牙齒表面,或以其他方式施用組成物至牙齒表面。
此外,本發明包括經由施用組成物至口腔表面(口腔之硬及軟組織),以增加或保持哺乳動物全身健康之方法。於此方法中使用之組成物可為任何上文所述之組成物,只要其含有至少:三氯沙、三氯沙單磷酸鹽、氯已定、阿來西定、海克西定、血根鹼、氯化芐烷銨、柳醯胺苯、溴化度米芬、氯化鯨蠟吡啶(CPC)、氯化十四基吡啶(TPC)、氯化N-十四基-4乙基吡啶(TDEPC)、奧替尼啶、地莫匹醇、辛哌醇、乳酸鏈球菌素、鋅離子劑、銅離子劑、精油、呋喃酮、細菌素、月桂醯精胺酸乙酯、木蘭萃取物、金屬離子源、碳酸氫精胺酸、異厚朴醇、厚朴醇、熊果酸、植酸、桑色素、沙棘萃取物、過氧化物、酶,山茶萃取物、類黃酮、黃烷、鹵化二苯基醚、肌酸、及蜂膠中之一者。施用可每日至少一次,而較佳每日高達五次,並且可進行一段時間,例如:一週、高達一年,高達三年或終身。
將參照下述非限制性實例說明各種具體實例。
製備具表1配方的牙劑組成物。對於實例1,牙劑組成物含有0重量%二氧化矽(索玻矽AC43(Sorbosil AC43)),及2重量%氧化鋅,封裝至一聚合物薄膜中,該薄膜含有兩種不同分子量之HPMC材料的組合,包括美多秀E5(Methocel E5)及美多秀E50(Methocel E50)。
為評估該牙劑配方之阻塞功效,自人類臼齒製備齒質小盤(dentin disks),將臼齒切片、打磨、拋光。最後,以6%檸檬酸蝕刻小盤,並以聲波處理,以打開齒質表面上的小管。每一小盤經機械牙刷及1:2重量比之水:牙劑,刷洗1分30秒。刷洗後,該小盤以水沖洗15秒,之後儲存於磷酸鹽緩衝液15分鐘。每一小盤重複此處理循環7次。第七次處理後,使用共軛焦顯微鏡進行小盤檢查。之後該小盤被置於1分鐘酸試驗(使用市售可樂碳酸飲料),並於每次處理後檢驗,以評估殘留在齒質小管之產物量。
結果顯示於圖1,由實例1可見,7次刷洗循環後,齒質小管具良好阻塞作用。經過使用可樂12次連續酸試驗循環後,齒質小管仍具良好阻塞作用。
於進一步酸試驗中,將該小盤之後暴露於使用6重量%檸檬酸的極度酸試驗30秒,並於每次處理後檢驗,以評估殘留在齒質小管之產物量。
結果顯示於圖2。由實例1可見,經過檸檬酸試驗後,該齒質小管已稍暴露。
對於對照例1,製備具表1配方之牙劑組成物,其含有(如實例1)0重量%二氧化矽(索玻矽AC43),但與實例1相較,修改為存在1重量%氧化鋅粉末,並且氧化鋅未封裝於聚合物薄膜中。
結果亦顯示於圖1,由對照例1可見,經7次刷洗循環後,齒質小管之阻塞作用不佳。使用可樂12次連續酸試驗循環之後,該齒質小管阻塞作用甚至更差。
實例1及對照例1的比較顯示,當採用與聚合物薄膜組合時,金屬氧化物粒子,特別是氧化鋅粒子,可提供良好齒質阻塞作用。
對於實例2,製備具表1配方之牙劑組成物,其包含5重量%二氧化矽(索玻矽AC43),還有2重量%氧化鋅粉末,封裝至聚合物薄膜中。
結果亦顯示於圖1。
由此可見,經7次刷洗循環後,齒質小管再次具良好阻塞作用。使用可樂12次連續酸試驗循環後,齒質小管再次具良好阻塞作用。
於進一步酸試驗中,將該小盤之後暴露於使用6重量%檸檬酸的極度酸試驗30秒,並於每次處理後檢驗,以評估殘留在齒質小管之產物量。
結果再次顯示於圖2。由實例2可見,經檸檬酸試驗後,該齒質小管仍然閉塞。實例1及實例2極度酸試驗之比較顯示:具5重量%二氧化矽粒子(AC43)與氧化鋅及黏著聚合物之配方較無二氧化矽粒子之配方,提供更佳的齒質小管阻塞作用。雖然依據實例1含有氧化鋅及聚合物之牙劑提供過敏功效,而依據實例1再添加之二氧化矽粒子顯示進一步提高阻塞作用功效。
對於對照例2,製備具表1配方之牙劑組成物,其包含(如實例2)5重量%二氧化矽(索玻矽AC43),但相較於實例1,修改為不存在氧化鋅。
對於對照例3,製備具表1配方之牙劑組成物,其包含(如實例2)5重量%二氧化矽(索玻矽AC43),但相較於例1,修改為存在1重量%氧化鋅粉末,且該氧化鋅粉末未封裝至聚合物薄膜中。
對照例2及3兩者之結果亦顯示於圖1。由對照例2及3兩者可見,經7次刷洗循環後,齒質小管之阻塞作用不佳。使用可樂12次連續酸試驗循環之後,該齒質小管阻塞作用甚至更差。
實例1及2與對照例2及3的比較顯示,當合併採用聚合物薄膜時,該金屬氧化物粒子,特別是氧化鋅粒子,可提供良好齒質阻塞作用,而在無此聚合物薄膜時,添加二氧化矽粒子無法提供良好的齒質阻塞作用。
對於對照例4,牙劑組成物包括申請人以商品名“全新靈敏”(Total Advance)出售之市售牙劑,其含有小粒子二氧化矽及黏附劑之組合。由圖1可見,與此已知牙劑相較,實例1及2之牙劑組成物提供更佳的齒質阻塞作用。
圖1顯示含有氧化鋅和聚合物薄膜之配方(實例1)較僅含有氧化鋅粉末之配方(對照例1)更能抵抗酸試驗。含有氧化鋅,AC43,及薄膜聚合物之配方(實例2)較含有AC43無氧化鋅、無聚合物(對照例2)或含有AC43及氧化鋅無聚合物(對照例3)之配方亦更能抵抗酸試驗。
這些結果建議該聚合物提高配方之功能,以承受酸試驗。這些結果亦證明氧化鋅與聚合物,或氧化鋅及AC43與聚合物之組合可阻塞齒質小管,並且可能提供與該市售全新靈敏牙劑不相上下之過敏緩解效果。
此外,於一液壓傳導實驗中評估實例1及2之牙劑組成物阻塞齒質小管,及於水流下維持阻塞作用的能力。
於此實驗中,齒質小盤被置放於一帕許小盒(pashely cell)內,以牙劑刷洗,且水流經該小盒,當該齒質小管發生阻塞時,通過齒質小盤之水流將減少。
表2顯示,與不含氧化鋅、AC43或聚合物之安慰劑配方相較,以實例1及2之牙劑組成物處理一次後,流量減少近一倍。此為進一步的證據表明,含有聚合物及氧化鋅及/或AC43之配方可以阻塞齒質小管。
此表顯示以潔牙劑僅一個處理循環刷洗後,增強的齒質阻塞作用。
圖1敘述以本發明之口腔保健組成物的兩個實例相對於四個對照例處理哺乳動物牙齒齒質基質造成之阻塞作用發生率的比較,一個對照例包含一已知市售減敏牙劑,以刷洗處理及第一次酸性接觸處理後,該基質顯示未處理狀。
圖2敘述經第二次酸性接觸處理之後,以圖1中說明之本發明口腔保健組成物的兩個實例處理哺乳動物牙齒齒質基質造成之阻塞作用發生率的比較。
Claims (8)
- 一種口腔保健組成物,其包含口腔可接受之載體;具有平均粒徑不大於齒質小管之金屬氧化物粒子;及用於黏著該金屬氧化物粒子於該齒質小管之聚合物黏著材料,其中該金屬氧化物包含氧化鋅;及其中該金屬氧化物封裝於聚合物黏著材料中且其中該金屬氧化物粒子係以0.5至2%重量比之組成物總重量存在,且其中該聚合物黏著材料包含具不同分子量的兩種羥烷基纖維素聚合物之混合物,其中至少一種羥烷基纖維素聚合物係選自由羥丙基甲基纖維素(HPMC)、羥乙基丙基纖維素(HEPC)、羥丁基甲基纖維素(HBMC)、及羧甲基纖維素(CMC)組成之群組。
- 根據申請專利範圍第1項之口腔保健組成物,其中該聚合物黏著材料包含至少一種聚合物,其選自包括:聚(環氧乙烷)聚合物、線狀聚乙烯吡咯啶酮(PVP)及經交聯之聚乙烯吡咯啶酮(PVP)、聚乙二醇(PEG)/聚丙二醇(PPG)共聚物、環氧乙烷(EO)-環氧丙烷(PO)嵌段共聚物、酯膠、蟲膠、感壓性聚矽氧黏著劑、甲基丙烯酸酯、或其混合物。
- 根據申請專利範圍第1項之口腔保健組成物,進一步包含二氧化矽粒子,其具有不大於齒質小管的平均粒徑。
- 根據申請專利範圍第3項之該口腔保健組成物,其中該二氧化矽粒子係以高達10%重量比之量存在,其以該口腔保健組成物之總重為基準。
- 根據申請專利範圍第4項之口腔保健組成物,其中該二氧化矽粒子係以3至6%重量比之量存在,其以該口腔保健組成物之總重為基準。
- 根據申請專利範圍第1項之口腔保健組成物,其為牙劑組成物。
- 根據申請專利範圍第6項之口腔保健組成物,其為牙膏或凝膠。
- 根據申請專利範圍第1項之口腔保健組成物,其中該組成物被配製成一形式,其選自漱口水、膠、可溶性錠劑,及可溶性薄片。
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| MX376901B (es) | 2025-03-07 |
| CA2791551A1 (en) | 2011-10-06 |
| JP5769795B2 (ja) | 2015-08-26 |
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| TW201201854A (en) | 2012-01-16 |
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| AU2010349781B2 (en) | 2013-07-11 |
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| US20130017238A1 (en) | 2013-01-17 |
| PH12012501677A1 (en) | 2016-09-09 |
| WO2011123121A1 (en) | 2011-10-06 |
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| ZA201206301B (en) | 2015-10-28 |
| EP2519215A1 (en) | 2012-11-07 |
| US20160193124A1 (en) | 2016-07-07 |
| RU2536435C2 (ru) | 2014-12-20 |
| BR112012021666B1 (pt) | 2017-05-02 |
| CN102821739B (zh) | 2015-07-29 |
| US11103431B2 (en) | 2021-08-31 |
| US9320699B2 (en) | 2016-04-26 |
| CN102821739A (zh) | 2012-12-12 |
| US10441516B2 (en) | 2019-10-15 |
| US20190380931A1 (en) | 2019-12-19 |
| MX343209B (es) | 2016-10-27 |
| JP2013523729A (ja) | 2013-06-17 |
| PL2519215T3 (pl) | 2017-02-28 |
| AU2010349781A1 (en) | 2012-09-06 |
| SG183296A1 (en) | 2012-09-27 |
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