201221145 六、發明說明： 【發明所屬之技術領域】 本發明提供一種用於牙齒再礦化之新穎化合物。特定而 言，本發明提供一種含雙重陰離子之磷酸鈣化合物，且特 別是提供由本成分產生與包含本成分之牙齒貼片及其它應 用於牙齒再礦化之衍生口腔保健用途。 【先前技術】 牙齒主要由琺瑯質（enamel)、牙本質（dentin)及富含神經 及血管之牙髓腔（pulp)構成。斑瑯質及牙本質由於含有高比 例之氫氧基鱗灰石（hydroxyapatite，HAp)而為高度約化之 硬組織。 在口腔環境中，液相（唾液）及固相（琺瑯質）中之磷酸根 及約離子在牙齒之去礦化（demineralization)與再礦化 (remineralization)作用間維持動態平衡狀態。去礦化為由 牙菌斑酸性代謝物或膳食酸性物引起之牙齒中礦物質成分 之氫氧基磷灰石發生溶解流失的過程，其反應式如下所 示：201221145 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention provides a novel compound for remineralization of teeth. In particular, the present invention provides a calcium phosphate compound containing a dual anion, and in particular, a dental oral preparation for the production of the component and a dental cosmetic comprising the component and other derivatized oral health applications for tooth remineralization. [Prior Art] The teeth are mainly composed of enamel, dentin, and a pulp that is rich in nerves and blood vessels. Cantharidin and dentin are highly-hardened hard tissues due to the high proportion of hydroxyapatite (HAp). In the oral environment, the phosphate and the ions in the liquid phase (saliva) and the solid phase (enamel) maintain a dynamic equilibrium between the demineralization and remineralization of the teeth. Demineralization is a process in which the hydroxyapatite of the mineral component of the tooth caused by the plaque acidic metabolite or dietary acid is dissolved and lost. The reaction formula is as follows:
Demineralization 10〇75CPO4)3Oi/ + 14/r、 \0Ca2+ + 6ff2PO~ + 2H20Demineralization 10〇75CPO4)3Oi/ + 14/r, \0Ca2+ + 6ff2PO~ + 2H20
Remineralization 去礦化可出現於牙齒表面或牙齒表層下，過度之去礦化會 導致動態平衡狀態之失衡而流失齒質，對牙齒之侵害程度 則視酸性物質之濃度、作用時間及pH值而定。然而，如能 抑制口腔細菌生長或緩衝源自碳酸飲料或細菌代謝所產生 之酸度，則可有助於牙齒琺瑯質之修復且防止/緩減齲齒發 147853.doc 201221145 生，從而避免牙齒敏感、疼痛，甚至牙齒脫落等後遺症。 當動態平衡狀態失衡時，顯示口腔中由唾液所提供之再 礦化作用已經不足以克服去礦化作用導致之齒質流失，而 無法自然地恢復牙齒之健康狀態。麟齒（dentai…㈣通常 由於口腔或唾液中酸性物f之侵㈣產生損害或麟洞，且 若鑛洞夠深m吏牙齒受引起腐狀細菌侵触。此等酸 性物易於由膳食碳水化合物經各種形成牙菌斑之生物體 (諸如變異鏈球菌（6·· 醱酵性分解代謝產生。諸多 研究已顯示食用可醱酵糖易引起牙菌斑pH值變化而低於琺 瑯質開始溶解之臨界水平（pH 5.5)。 唾液因含過飽和之磷酸鈣無機鹽具有天然性保護與對抗 牙齒去礦化之功能。牙齒之再礦化係指無機鹽類之鈣離子 與磷酸根離子於牙齒表面以沉積後再結晶之方式來修復遭 酸敍脫鈣之牙齒結構的過程。 增加再礦化及抑制去礦化則為緩解或修復齲齒之重要機 制之 因此’ 一般多藉由人為方式補充增加口腔環境中 磷酸根離子及鈣離子之濃度來增進再礦化作用以克服齒質 流失之失衡狀態。在各種磷酸鈣鹽中，非晶性磷酸飼 (amorphous calcium phosphate，ACP; Ksp: 1〇·24 8)由於其 具有較佳之溶解度’而可成為鈣離子及磷酸根離子之優良 來源。然而’ ACP材料在生理環境中與水接觸後，容易經 相轉變而轉化為低溶解度之氫氧基磷灰石（CaiQ(p〇4)6(〇H)2 ; ksp: urm8)〇此外，當ACp溶解解離後之鈣離子及磷酸 根離子或無法於口腔中或牙齒表面之滯留足夠長之時間， 147853.doc 201221145 將不易充分發揮再礦化之功能^ 2004年，澳大利亞 (Australia)墨爾本大學（university 〇f Melb〇urne)之 EricRemineralization can occur on the surface of teeth or under the surface of teeth. Excessive mineralization can lead to imbalance of dynamic equilibrium and loss of tooth quality. The degree of damage to teeth depends on the concentration of acid, time of action and pH. . However, if it can inhibit the growth of oral bacteria or buffer the acidity produced by carbonated beverages or bacterial metabolism, it can help the repair of tooth enamel and prevent/slow the decay of dental caries, thus avoiding tooth sensitivity and pain. And even sequelae such as tooth loss. When the dynamic equilibrium state is unbalanced, it is shown that the remineralization provided by saliva in the oral cavity is insufficient to overcome the loss of tooth loss caused by demineralization, and the state of health of the teeth cannot be naturally restored. Lintai (deni... (4) usually produces damage or lining due to the intrusion of acidic substances f in the mouth or saliva, and if the mine is deep enough, the teeth are invaded by causing rotted bacteria. These acids are easily replaced by dietary carbohydrates. Various plaque-forming organisms (such as Streptococcus mutans (6·· lysate catabolism. Many studies have shown that eating sucrose can easily cause plaque pH changes and below the critical level at which enamel begins to dissolve) (pH 5.5) Saliva has a natural protective effect against tooth demineralization due to the supersaturated calcium phosphate inorganic salt. Remineralization of teeth refers to the deposition of calcium ions and phosphate ions of inorganic salts on the tooth surface. Recrystallization to repair the structure of the acid-decalcified tooth structure. Increasing remineralization and inhibiting demineralization are important mechanisms for relieving or repairing dental caries. 'Generally, it is supplemented by artificial means to increase the phosphoric acid in the oral environment. The concentration of root ions and calcium ions promotes remineralization to overcome the imbalance of tooth loss. Among various calcium phosphate salts, amorphous phosphate feed (amorphous calciu) m phosphate, ACP; Ksp: 1〇·24 8) It is an excellent source of calcium ions and phosphate ions because of its better solubility. However, 'ACP material is easy to undergo phase transformation after contact with water in physiological environment. And converted to low solubility of hydroxyapatite (CaiQ(p〇4)6(〇H)2; ksp: urm8) 〇 In addition, when ACp dissolves dissociated calcium ions and phosphate ions or can not be in the mouth Or the retention of the tooth surface is long enough, 147853.doc 201221145 will not fully play the role of remineralization ^ 2004, Australia (Australia) University of Melbourne (university 〇f Melb〇urne) Eric
Reynolds使用由酶裂解之酪蛋白所產生之胜肽片段作為載 體與ACP螯合以形成酪蛋白磷酸胜肽_非晶性磷酸鈣複合物 (casein phosphopeptide-amorphous calcium phosphate, CPP-ACP)，使ACP之非晶性結構得以因酪蛋白填酸胜肽之包覆 構成核-殼（core-shell)結構而穩定化，以防止Acp轉化為低 溶解度之結晶性磷酸鈣。而可維持ACp之高溶解度，而酪 蛋白攝酸胜肽並具有良好之口腔黏膜附著性 (mucoadhesion)，可以延長ACP附著於口腔表面之滯留時 間，維持ACP預防齲齒之功效。儘管cpp_Acp可有效預防 麟齒，但由於赂蛋白在某些過敏性體質之個人中具引發乳 糖不耐症（lactose intolerance)之風險而受限。 臺灣專利公開案第200637587號（美國專利申請案第 1 1/020,010號）揭示一種包含木糖醇之口腔護理組合物。儘 管該組合物可降低口腔酸度且防止齲齒，但該組合物並不 具再礦化之功能。 臺灣專利公開案第200637605號（美國專利申請案第 1 1/256,861號）揭示一種牙膏組合物，其包含濕潤劑、研磨 劑及包括熊果酸及鼠尾草酸（carnosic acid)之抗細菌組分。 該申請案係關於抗細菌調配物，與再礦化並無相關。 臺灣專利公開案第200640531號（美國專利申請案第 1 1/256,788號）揭示一種口腔護理組合物，其包含用於抑制 細囷且防止牙菌斑、炎症及氧化之牛至（oregan〇)。然而， 147853.doc 201221145 該組合物不能提供再礦化作用。 美國專利第 5,037,639號、第 5,268，167號、第 5,437,857 號、第5,427,768號及第5,460,803號涉及各種用於再礦化之 非晶性磷酸鈣化合物（諸如非晶性磷酸鈣（ACp)、非晶性氟 化磷酸鈣（ACPF)及非晶性碳酸磷酸鈣（Accp))。然而，由 於此等ACP非晶性磷酸鈣化合物會在與水接觸後結晶，而 影響其最佳功能之發揮。 美國專利第5,858,333號提供一種能夠在牙齒中再礦化表 面下彳貝害及/或礦化暴露之牙質小管的兩部分口腔產品， 其由陽離子個別部分與陰離子個別部分構成。陽離子個別 部分中含有ACP。然而，該產品中之Acp不能保持與牙齒 持續長時間接觸’所以其再礦化作用並不顯著。 美國專利申請案第200801 71001號提供新型牙膏，其包 含酪蛋白磷肽非晶性磷酸鈣，且其再礦化作用亦不令人滿 意。臺灣專利申請案第200637587號使用甘油磷酸鈣使牙 齒再礦化。然而，在甘油磷酸鈣中之鈣離子係鍵結至甘油 磷酸根，而非分別鍵結至甘油與磷酸根，且甘油磷酸鈣之 溶解度相對較低。 因此，仍需要研發具有再礦化作用之物質。 【發明内容】 本發明之一目的在於提供具有下式之含雙重陰離子之磷 酸舞化合物： (Ca + 2)x(陰離子-a)y(p〇4-3)z 其中 2x=(a*y+3z); 147853.doc 201221145 a為1至3之整數；且χ、yAz中之每—者皆不為〇。 本發明之另-目的在於提供—種牙齒護理組合物，其包 3本&明之含雙重陰離子之磷酸鈣化合物及附加之口腔可 接受之载劑。 本發明之另一目的在於提供一種用於牙齒再礦化之貼 片〜、有包S本發明之含雙重陰離子之磷酸約化合物或 組合物的牙齒黏附層及支撐層。 【實施方式】 本發明發現-種具有新類型分子結構之含雙重陰離子之 磷_化合物。出乎意外的是，本發明之含雙重陰離子之 侧化合物因其具有穩定之非結晶性結構，使其且有穩 定之高溶解度優點，所以亦可增進再礙化，修復遭脫每去 礦化之牙齒，甚至以再礦化之機制，提供牙質小管密 效果與持久性。 本發明提供具有下式之含雙重陰離子之磷酸鈣化合物： (Ca+2)x(陰離子-a)y(p〇4-3)z 其中 2x=(a*y+3z); a為1至3之整數；且 X、y及z中之每一者皆不為〇。 本文中’ 「包含」意謂可添加不影響最終結果之其他步 驟及其他成分。此術語涵蓋術語「由·....組成」及/ ’ 上由……組成」。 ’’」 基本 「牙齒護理組合物」係指在常規使用過程中並非用 镇以達成全身性投予特定治療劑之目的，而是保留於口腔 147853.doc 201221145 中足夠長時間以接觸實質上所有牙齒表面及/或口腔組織 以達成發揮該成分在口腔中提供功能活性目的之產品。本 發明之牙齒護理組合物可呈牙膏、潔牙液、牙粉、慕絲 (mousse)、局部口腔凝膠劑、漱口水、假牙產品、口腔喷 霧、口含錠、口腔錠劑、糖衣錠、牙齒貼片或口香糖之形 式。 如本文所用之術語「牙齒」係指天然牙齒以及人造牙或 假牙。 如本文所用之術語「口腔可接受之載劑」意謂用於本發 明組合物中之任何安全且有效之物質。該等物質包括氟離 子來源’牙結石抑制劑（anticalculus agent);其他再礦化 劑，諸如約離子來源、磷酸根離子來源及鋰離子來源；緩 衝劑；研磨拋光物質；牙齒增白劑或漂白劑，諸如過氧化 物來源；鹼金屬碳酸氫鹽；增稠物質；保濕劑；水；界面 活性劑，二氧化鈦；調味系統；甜味劑；木糖醇；著色 劑；及其混合物。 術°° 礦化」與「再礦化」可互換使用且係指無機鹽在 牙齒結構中結晶。 根據本發明，「含雙重陰離子之磷酸鈣化合物」為一種 複合物’其具有含有處於核心之雄酸鈣及圍繞麟酸鈣之 約-陰離子的單元以使鈣、陰離子及磷酸根形成下式： (Ca )χ(陰離子·a)y(p〇4-3)z，其中 2x = (a*y + 3z)，ra」為以 3之整數，且X、丫及2中之每一者皆不為〇。另外，符號 」忍謂乘°磷酸鈣與陰離子之間的結合依賴於離子-離 147853.doc 201221145 子鍵結。由於陰離子鍵結至鱗酸約結構中，所以與碟酸弼 相比，含雙重陰離子之磷酸飼化合物在水性環境中為非晶 性而能維持穩定之高溶解度。 ^述結構使本發明之含雙重陰離子之鱗酸弼化合物具有 ，晶=。然而’由於此化合物在水性溶液中之溶解度及穩 疋性阿，所以約、鱗離子之持續釋放，從而增加再礦化作 用與促進牙齒損害之修復。 ,么月之3雙重陰離子之磷酸鈣化合物係藉由以下方式 來製備：提供約離子溶液、陰離子溶液及磷酸根陰離子溶 液’此合二種溶液以形成含雙重陰離子之碌酸弼化合物； 及移除沈殿物。根據本發明’含雙重陰離子之鱗_化合 物之製備可進一步包括乾燥步驟。 根據本發明’約離子來源及碌酸根離子之來源可為單一 化。物、單一化合物之混合物或個別化合物。鈣離子可來 自任何無_化合物或有機約化合物，且罐酸根陰離子可 來自任何磷酸鹽化合物。適宜之飼及填酸根離子單一來源 包括（但不限於）無水碟酸二舞、磷酸四約、二水合碟酸二 妈、鱗酸三約及其混合物。適宜之飼離子及碌酸根離子個 別來源為例如氣化角、硫_、紹石夕㈣、碳_、氯化 鈣、抗壞血酸鈣、氣化钲、3 S π k . ^ 礼化鈣虱氧化鈣、乳酸鈣、檸檬酸鈣 或葡糖酸弼作為1弓離子夾、、局 B * 7雕十孓源，以及磷酸鈉或磷酸鉀作為磷 酸根離子來源。 根據本發明’陰離子之來源為任何鹵化物、無機酸或有 機酸。較佳地’陰離子之來源為有機酸。適合之無機酸陰 147853.doc 201221145 離子包括（但不限於）硝酸根、硫酸根、齒離子及碳酸根。 適合之有機酸陰離子包括（但不限於）乳酸根、檸檬酸根、 乙酸根、酒石酸根、順丁烯二酸根、丁二酸根、丙酮酸 根、羥乙酸根、戊二酸根、丙二酸根及鄰苯二甲酸根。 含雙重陰離子之磷酸鈣化合物之較佳實施例包括（但不 限於）乳酸磷酸鈣、檸檬酸磷酸鈣、硫酸磷酸鈣及順丁烯 二酸填酸鈣。最佳地’令雙重陰離子之磷酸鈣化合物為具 有下式之乳酸磷酸鈣：Ca9L12P2，且Ca/P比為約4.5。乳酸 磷酸鈣形成八面體結構，其中磷酸三鈣位於結構中心，且 乳酸根-約-乳酸根位於結構之頂點上。如上文所提及，含 陰離子之構酸約化合物之溶解度增加。舉例而言，此項技 術中已知用於牙齒再礦化之物質甘油磷酸飼與乳構酸約之 溶解度為每100 ml水2.0 g與每1〇〇 mi水0 3-1.0 g，而乳酿 磷酸鈣之溶解度為每1 〇〇 ml水3.丨至丨丨丨g。 在另一態樣中，本發明提供一種牙齒護理組合物，其包 含本發明之含雙重陰離子之磷酸鈣化合物及另外的口腔可 接受載劑。 在製備本發明組合物時，需要將一或多種水性載劑添加 至組合物中。該等物質在此項技術中為熟知的且易於由熟 習此項技術者基於所製備之組合物所需之物理及美學特性 來選擇。此等載劑可以不干擾或抑制本發明之含陰離子之 填酸妈化合物之作用的含量納人。水性載劑通常佔以口腔 4理、，且σ物之重量計約5〇%至約99%，較佳約至約 98% ’且更佳約80%至約95%。 147853.doc •10- 201221145 本發明組合物可含有緩衝劑。如本文所用之緩衝劑係指 可用於將組合物之pH值調節至約pH 4至約PH 10之範圍内 的試劑。含有聚合礦物質表面活性劑之牙齒護理組合物之 漿料pH值通常為約4至約1 〇 ’較佳為約4.5至約8且更佳為 約5.5至約7。緩衝劑包括驗金屬氫氧化物、碳酸鹽、倍半 碳酸鹽、硼酸鹽、矽酸鹽、磷酸鹽、咪唑及其混合物。特 定緩衝劑包括磷酸單鈉、磷酸三鈉、氫氧化鈉、氫氧化 鉀、鹼金屬碳酸鹽、碳酸鈉、咪唑、焦磷酸鹽、檸檬酸及 擰檬酸鈉。緩衝劑之使用量為以本發明組合物之重量計約 0.1%至約55%，較佳約1%至約3〇%或約1%至約1〇%且更佳 約1.5%至約3% » 本發明組合物可視情況含有牙結石抑制劑，諸如乳酸 鈣 '乳磷酸鈣、乳酸鈣之複鹽及其混合物、γ_聚麩胺酸^ PGA)、焦磷酸鹽及其他聚賴鹽。其中焦填酸鹽為最眾 所周知之用於牙齒護理產品者。焦磷酸鹽可在本發明中用 作牙結石抑制劑或緩衝劑。適用於本發明組合物中之焦項 S夂鹽包括一鹼金屬焦磷酸鹽、四鹼金屬焦磷酸鹽及其混合 物呈未水α及水合形式之焦麟酸二氮二納、焦碟酸四銷 及焦鱗酸四鉀為較佳物f ^其他可替代㈣酸鹽使用或幽 焦填酸鹽組合使用之牙結石抑制劑包括諸如合成陰離子聚 合物之已知物質。 研磨拋光物質亦可納入牙齒護理組合物中。 發明之組合物中之研磨拋光物質可為不過度研磨牙質之妇 何物質。研磨拋光物質應以不損害任何成分(尤其氣則 147853.doc 201221145 來源及含有聚合劑之聚磷酸鹽）之穩定性的方式調配於牙 齒護理組合物令。典型研磨拋光物質包括二氧化石夕凝膠及 沈澱物；氧化鋁；磷酸鹽’包括正磷酸鹽、聚偏磷酸鹽及 焦填酸鹽；及其混合物。特定實例包括二水合正構酸二 鈣、焦磷酸鈣、填酸三鈣、聚偏碟酸鈣、不溶性聚偏磷酸 鈉、水合氧化鋁、β焦磷酸鈣、碳酸鈣、樹脂研磨物質（諸 如脲與曱搭之微粒狀縮合產物）及諸如美國專利第 3,070，510说中所揭不之其他研磨抛光物質。亦可使用研磨 劑之混合物。 本發明組合物可包括牙齒增白劑或漂白劑。適用於增白 之活性劑係選自由以下組成之群：過氧化物、金屬亞氣酸 鹽、過硼酸鹽、過碳酸鹽、過氧酸、過氧硫酸鹽及其組 合。適合之過氧化物化合物包括過氧化氫（hydr〇gen peroxide)、過氧化鈣（Ca〇2, Calcium per〇xide)、碳醯胺過 氧化物（carbamide peroxide’ 是-種過氧化脲（Urea per〇xide) 及其混合物。適合之金屬亞氣酸鹽包括亞氯酸鈣、亞氣酸 鋇、亞氣酸鎂、亞氯酸鋰、亞氣酸鈉及亞氣酸鉀。其他增 白活性劑可為次氯酸鹽及二氧化氣。較佳之亞氣酸鹽為亞 氣酸鈉。較佳之過碳酸鹽為過碳酸鈉。較佳之過氧硫酸鹽 為過硫酸氫鉀。本發明組合物可含有以本發明組合物之重 量計約0.01%至約1〇% ,較佳約〇.1%至約5%，更佳約〇2% 至約3。/。且最佳約0.3%至約〇.8%之牙齒增白活性劑。 本發明提供呈牙膏、潔牙液、牙粉、局部口腔凝膠劑、 漱口水、假牙產品、口腔喷霧、口含錠、可咀嚼口腔錠 147853.doc •12· 201221145 劑、口香糖形式、牙齒貼片的組合物。此等組合物向來含 有一些增稠物質或黏合劑以提供合意之稠度。較佳增稠劑 為羧基乙烯聚合物、角叉菜膠、羥乙基纖維素及纖維素醚 之水溶性鹽（諸如羧曱基纖維素鈉及羥乙基纖維素鈉）。亦 可使用天然膠’諸如刺梧桐樹膠（gum karaya)、三仙膠、 阿拉伯膠（gum arabic)及黃蓍膠。可使用膠狀矽酸鎂鋁或 細粉狀二氧化矽作為增稠劑之一部分以進一步改良質地。 增稠劑的使用量可為本.發明組合物之約〇 · 1重量％至約15重 量％。 本文所需之組合物之另一視情況選用之組分為保濕劑。 保濕劑用以避免牙膏組合物在暴露於空氣後硬化，且某些 保濕劑亦可賦予牙膏組合物合意之甜味。適用於本發明中 之保濕劑包括甘油、山梨糖醇、聚乙二醇、丙二醇及其他 可食用之多元醇。 本發明組合物亦可包含界面活性劑，其亦通常稱作起泡 劑（sudsmg agent)。適合之界面活性劑為在大範圍之值 内相當穩定且發泡之界面活性劑。界面活性劑可為陰離子 型界面活性劑、非離子型界面活性劑、兩性界面活性劑、 兩性離子型界面活性劑、陽離子型界面活性劑或其混合 物。 多種其他物質可併入本發明組合物令。其實例為著色 或增白劑、防腐劑、聚胡氧、葉綠素化合物及氨化物 (諸如脲、磷酸二銨及其混合物）。此等佐劑可在實質上 影響特性及特徵之量併人組合物中’且該等量視所涉及. I47853.doc -13- 201221145 特疋製劑類型而適當選擇。 劑出於某些㈣’可能需要在本發明組合物令包括抗細菌 ^何ΐ合，調味或甜味物質可用於調配本發明組合物之 〜°调味組分之實例包括調味油（例如綠薄荷油、 胡椒薄何油、鹿蹄草油、黃樟油、丁香油、鼠尾草油按 樹油、馬郁蘭油、肉桂油、擦檬油及撥油）以及水揚酸甲 西曰。適合之甜味劑包括薦糖、乳糖、麥芽糖、山梨糖醇、 環己胺基磺酸納及糖精。適合調味劑與甜味劑可一起佔組 合物之約〇.01%至5%或5%以上。 本發明之含雙重陰離子之磷酸鈣化合物或組合物可以 (但不限於）牙f、牙粉、潔牙液、漱口水、慕絲、假牙產 品、局部口腔凝膠劑、口腔錠劑、口含键、糖衣旋、口香 糖及牙齒貼片之形式應用。 在一實施例令，本發明之含雙重陰離子之磷酸鈣化合物 或、’且σ物可以牙齒貼片之形式用於再礦化。根據本發明之 貫施例，用於牙齒再礦化之貼片包含有含本發明之含陰 離子之磷酸鈣化合物或組合物的牙齒黏附層及支撐層。在 本發明之另一實施例中，貼片可進一步包含有含一或多種 牙齒活性成分的一或多層。熟習此項技術者可根據貼片之 應用決定層數。該牙齒黏附層在黏附至牙齒表面後釋放鈣 離子及碟S交根陰離子’且其具有親水特性及較佳的黏附強 度。根據本發明之實施例，除本發明之含陰離子之磷酸鈣 化合物或組合物之外，該牙齒黏附層亦包含一或多種牙齒 147853.doc 201221145 活性成分。 根據本發明，支撐層在此項技術中為已知的且其包含不 溶於水之物質。該不溶於水之物質之實例包括（但不限於） 耐光性紙、鄰苯二甲酸乙酸纖維素、聚乙酸乙烯酯、乙基 纖維素、聚甲基丙烯酸甲酯、甲基丙烯醯基乙基甜菜鹼/ 曱基丙稀酸S旨共聚物（其可以由Mitsubishi製造之Yukaformer 商標名購得）、甲基丙烯酸共聚物（諸如Eudragit L 100、 Eudragit L 125、Eudragit L 100-55、Eudragit L 30D-55)、 曱基丙蝣酸胺基烧醋共聚物（諸如Eudragit E 1 00、Eudragit E 125、Eudragit RL 100、Eudragit RL 30D)或其混合物。 除本發明之含雙重陰離子之磷酸鈣化合物或組合物之 外，貼片之牙齒黏附層可含有親水性聚合物。根據本發 明，聚合物可為（但不限於）聚烷基乙烯醚-順丁烯二酸共聚 物（PVM/MA共聚物），諸如 Gantrez AN 119、AN 139及 S-97 ;聚乙稀醇；聚丙烯酸；泊洛沙姆（Poloxamer)407 (Pluronic) Pluronic F127 ;聚乙稀。比洛α定酮-乙酸乙稀酉旨 共聚物（PVP/VA共聚物），諸如 Luviskol VA及 Plasdone S PVP/VA ;聚氧化乙烯（Polyox);聚乙烯吡咯啶酮（PVP，K-15.about.K-120);聚四級敍-ll(Polyquaterium-ll)(Gafquat 755N)；聚四級銨-39(Merquat plus 3330);羧基聚亞曱基 (Carbopol);羥丙基甲基纖維素；羥乙基纖維素；經丙基 纖維素；凝膠；明膠；及褐藻酸鹽，諸如褐藻酸鈉。上述 聚合物可單獨或組合使用。聚乙烯吡咯啶酮（PVP)為最佳 之親水性聚合物。此等聚合物之溶劑包括水、乙醇或其混 147853.doc -15- 201221145 合物。此外，其他有機溶劑，諸如乙酸乙酯、二氯甲烷、 異丙醇、乙腈或其不同比率之混合物亦可用作溶劑。 欲附著至牙齒上之貼片應具足夠可撓性使其可變形，從 而使其順應牙齒之輪廓。由於一些聚合物之可撓性不良 所以可添加適合之塑化劑。聚丙二醇、甘油及聚乙二I 般用作塑化劑。 本發明之貼片可進一步包含使牙齒增白之增白劑、預防 鱗齒之氟離子或減輕齒齦炎或牙菌斑之亞錫離子。 本發明之貼片可進一步包含具有各種顏色之顏料、調味 劑'甜味劑及潤濕劑。顏料係用以使牙齒更白，且其係選 自由二氧化鈦、滑石、氫氧㈣灰石、氧化鋅及其混合物 組成之群。調味劑之實例包括胡椒薄荷、綠薄荷、鹿蹄 草、鼠尾草、桉樹油、水楊酸甲酯及其他水果萃取物。甜 味劑及潤濕劑之實例包括甘露糖醇、木糖醇、乳糖、阿斯 巴甜糖及糖精鈉。 實例 實例1製備具有高溶解度之乳酸磷酸鈣 將0.85 g氧化鈣（Ca〇)、2.81 g乳酸及〇12 g碟酸在96 22 g去離子水中混合。過濾所得混合物且乾燥，形成乳酸磷 酉文鈣化合物粉末，由於添加乳酸根，所以乳酸磷酸鈣化合 物具有不規則分子結構以及低結晶度及高溶解度。另外， 乳酸磷_化合物在水中較，因此將不會出現相轉變。 因此，鈣離子及磷酸根離子可自乳酸磷酸鈣化合物中釋 放從而可維持且增進有效的牙齒再礦化。藉由χ_射線繞 N7853.doc -16- 201221145 射（XRD)測定乳酸磷酸鈣化合物之結構，且其xRD繞射圖 本於圖1中。乳酸磷酸鈣化合物之溶解度為每1 〇〇 ml H20 3.1-11.1 g 〇 實例2 本發明之再礦化貼片及再礦化檢定 本發明之貼片包括牙齒黏附層及支撐層。貼片之牙齒黏 附層包含1.5 wt%聚-γ_麩胺酸（γ-PGA)、2.5 wt%甘油、3 wt%本發明之乳酸磷酸鈣化合物、10 wt%聚乙烯吡咯啶酮 (PVP)及83 wt%去離子水。貼片之支撐層包含2〇 wt%乙基 纖維素、10 wt%甘油及7〇 wt%乙醇。 將本發明之再礦化貼片置放於37〇c及1〇〇0/。濕度之模擬 口腔環境中以評估貼片中之乳酸磷酸鈣簇在溫熱及潮濕之 口腔環境中是否穩定。如圖2之XRD繞射圖中所示，乳酸 磷酸鈣簇在第〇分鐘、第3〇分鐘、第i天及第9天之XRD概 況保持相同，因此乳酸磷酸鈣簇中未出現相轉變。貼片在 使用期間維持有利之穩定性。 使用含有2 wt%及3 wt%乳酸磷酸鈣之本發明貼片、去離 子水作為空白對照、人工唾液作為陽性對照以及非晶性磷 酸鈣（ACP)/水（W)及γ_聚麩胺酸（y_pGA)_Acp/水（w)作為比 較實例來評估貼片之再礦化作用。藉由使用i M乙酸侵钱 牙is(表面3分鐘，將貼片附著至牙齒以再礦化，接著用微 硬度測試儀量測牙齒之努普微硬度（Knoop microhardness) (努普硬度數，KHN)來驗證再礦化貼片之有效性^再礦化 係以牙齒顯微硬度恢復百分比來量測： 147853.doc -17- 201221145 在使用貼片後15至30分鐘内出現牙齒再礦化。微硬度恢 復（％)與處理時間之相關性示於下表中： 去離子水 人工唾液 2% CLP貼片 3% CLP貼片 ACP/W γ-PGA-ACP/W 0分鐘 0.0 0.0 0.0 0.0 0.0 0.0 15分鐘 24.7 7.9 16.6 57.5 3.4 7.2 30分鐘 23.7 10.6 37.7 66.2 0.6 10.1 3天 17.3 23.1 45.1 78.7 13.0 51.9 上表之結果示於圖3中。如圖3中所示，具有2% CLP或 3% CLP之貼片提供有利之再礦化。在顯微鏡下檢查在用 本發明貼片處理後〇分鐘、2天、2天又23小時30分鐘及2天 又23小時45分鐘的牙齒。如圖4中所示，牙齒中之因微硬 度量測時留下之標記隨時間推移變得愈來愈小。結果表明 本發明之貼片具有修復牙齒之作用。 實例3 本發明之其他高溶解度複合物的溶解度及再礦 化檢定 使用碳酸鈣、硫酸鈣、氫氧化鈣或檸檬酸鈣、擰檬酸、 乙酸、乳酸或順丁烯二酸及磷酸鹽形成鈣-陰離子磷酸鹽 複合物粉末，且根據實例1中所提及之方法測定乳酸磷酸 鈣複合物之溶解度。所得複合物溶解度高於每iOO ml H20 3.0 g °在再礦化檢定中，將鈣-陰離子磷酸鹽複合物製備 成貼片且根據實例2之方法測定所得貼片之顯微硬度恢復 百分比°所得貼片硬度恢復百分比在15分鐘、30分鐘及3 天後分別高於50%、60%及70%。 【圖式簡單說明】 147853.doc -18- 201221145 圖1顯示本發明之乳酸磷酸鈣之x_射線繞射圖（xrd)。 圖2顯示乳酸磷酸鈣置於模擬口腔環境中〇分鐘、分 鐘、1天及9天後之XRD數據。 圖3顯示CLP貼片之微硬度恢復百分比（％)與處理時間的 相關性，其中符號「◊」表示去離子水，符號「α」表示 人工唾液，符號「△」表示2〇/〇 CLP貼片且符號「χ」表示 3% CLP貼片。 圖4顯示關於在用本發明貼片處理後牙齒中因微硬度量 測時留下之標記恢復的照片。 147853.docReynolds uses a peptide fragment produced by enzymatically cleaved casein as a carrier to chelate with ACP to form casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), which enables ACP The amorphous structure is stabilized by the coating of the casein-filled peptide to form a core-shell structure to prevent conversion of Acp to low solubility crystalline calcium phosphate. It can maintain the high solubility of ACp, and the casein acid peptide has good oral mucoadhesion, which can prolong the retention time of ACP attached to the oral surface and maintain the effect of ACP on preventing dental caries. Although cpp_Acp is effective in preventing nucleus, it is limited by the risk of lactose intolerance in individuals with certain allergies. An oral care composition comprising xylitol is disclosed in Taiwan Patent Publication No. 200637587 (U.S. Patent Application Serial No. 1/020,010). Although the composition reduces oral acidity and prevents dental caries, the composition does not function as a remineralization. Taiwan Patent Publication No. 200637605 (U.S. Pat. . This application relates to antibacterial formulations and is not related to remineralization. Taiwan Patent Publication No. 200640531 (U.S. Patent Application Serial No. 1/256,788) discloses an oral care composition comprising oregano for inhibiting plaque and preventing plaque, inflammation and oxidation. However, 147853.doc 201221145 this composition does not provide remineralization. U.S. Patent Nos. 5,037,639, 5,268,167, 5,437,857, 5,427,768, and 5,460,803 relate to various amorphous calcium phosphate compounds for remineralization (such as amorphous calcium phosphate (ACp), amorphous Calcium fluoride phosphate (ACPF) and amorphous calcium carbonate phosphate (Accp). However, since such ACP amorphous calcium phosphate compounds crystallize upon contact with water, they affect their optimum function. U.S. Patent No. 5,858,333 provides a two-part oral product capable of remineralizing mussels and/or mineralized exposed dentinal tubules in a tooth, which consists of a cationic individual portion and an anionic individual portion. The individual part of the cation contains ACP. However, Acp in this product does not remain in contact with the teeth for a long time, so its remineralization is not significant. U.S. Patent Application No. 200801 71001 provides a novel toothpaste containing casein phosphopeptide amorphous calcium phosphate and its remineralization is also unsatisfactory. Taiwan Patent Application No. 200637587 uses calcium glycerophosphate to remineralize teeth. However, the calcium ion in the calcium glycerophosphate is bonded to the glycerol phosphate instead of the glycerol and phosphate, respectively, and the solubility of the calcium glycerophosphate is relatively low. Therefore, there is still a need to develop a substance having remineralization. SUMMARY OF THE INVENTION One object of the present invention is to provide a phosphoric acid dance compound having a double anion having the formula: (Ca + 2) x (anion-a) y (p 〇 4-3) z wherein 2 x = (a * y +3z); 147853.doc 201221145 a is an integer from 1 to 3; and each of χ, yAz is not 〇. Another object of the present invention is to provide a dental care composition comprising a dual calcium anion calcium phosphate compound and an additional orally acceptable carrier. Another object of the present invention is to provide a patch for tooth remineralization, a dental adhesive layer and a support layer comprising a double anion-containing phosphate compound or composition of the present invention. [Embodiment] The present invention has found a phosphorus-compound containing a double anion having a novel type of molecular structure. Surprisingly, the double anion-containing side compound of the present invention has a stable and non-crystalline structure, and has the advantages of stable high solubility, so that it can also enhance re-inhibition, repair and de-mineralization. The teeth, even with the mechanism of remineralization, provide dentin tube compaction and durability. The present invention provides a calcium phosphate compound having a double anion having the formula: (Ca+2)x(anion-a)y(p〇4-3)z wherein 2x=(a*y+3z); a is 1 to An integer of 3; and each of X, y, and z is not 〇. The term 'include' in this document means that other steps and other ingredients that do not affect the final result can be added. This term covers the terms "consisting of." and /' consisting of. ''" Basic "dental care composition" means not for the purpose of achieving a systemic administration of a specific therapeutic agent during routine use, but remains in the oral cavity 147853.doc 201221145 for a sufficient period of time to contact substantially all The tooth surface and/or the oral tissue is a product that achieves the purpose of providing functional activity of the component in the oral cavity. The dental care composition of the present invention may be a toothpaste, a dentifrice, a dentifrice, a mousse, a topical oral gel, a mouthwash, a denture product, an oral spray, an ingot, an oral lozenge, a sugar lozenge, a tooth. Patch or chewing gum form. The term "teeth" as used herein refers to natural teeth as well as artificial teeth or dentures. The term "orally acceptable carrier" as used herein means any safe and effective substance for use in the compositions of the present invention. Such materials include fluoride ion sources 'anticalculus agents; other remineralizing agents such as about ion sources, phosphate ion sources and lithium ion sources; buffers; abrasive polishing materials; tooth whitening agents or bleaching Agents, such as peroxide sources; alkali metal hydrogencarbonates; thickening materials; humectants; water; surfactants, titanium dioxide; flavoring systems; sweeteners; xylitol; colorants; "°° mineralization" is used interchangeably with "remineralization" and refers to the crystallization of inorganic salts in the tooth structure. According to the present invention, a "calcium phosphate compound containing a double anion" is a complex having a unit containing a calcium orthocalcate at the core and an about-anion surrounding the calcium cinnamate to form calcium, an anion and a phosphate into the following formula: Ca )χ(anion·a)y(p〇4-3)z, where 2x = (a*y + 3z), ra" is an integer of 3, and each of X, 丫 and 2 is not Why? In addition, the symbol "bearing" multiplication between calcium phosphate and anion relies on ion-ion 147853.doc 201221145 sub-bonding. Since the anion is bonded to the sulphuric acid structure, the phosphoric acid compound containing the double anion is amorphous in an aqueous environment and maintains a stable high solubility compared to the strontium silicate. The structure is such that the double anion-containing bismuth citrate compound of the present invention has a crystal =. However, due to the solubility and stability of the compound in an aqueous solution, the sustained release of the scaly ions increases the remineralization and promotes the repair of tooth damage. , the month of the double anion calcium phosphate compound is prepared by: providing about ionic solution, anion solution and phosphate anion solution 'the two solutions to form a double anion-containing bismuth citrate compound; In addition to the Shen Temple. The preparation of the double anion-containing scale-compound according to the present invention may further comprise a drying step. According to the present invention, the source of the about ion source and the sulphonate ion can be singular. a mixture of compounds, individual compounds or individual compounds. The calcium ion can be derived from any compound or organic compound, and the can alkate can be derived from any phosphate compound. Suitable sources of feed and acidate ions include, but are not limited to, anhydrous disc acid dance, phosphoric acid tetradecyl, dihydrated acid diammonium, squary tris and mixtures thereof. Suitable individual sources of feed ions and acid ions are, for example, gasification angle, sulfur_, Shao Shixi (four), carbon_, calcium chloride, calcium ascorbate, gasified phlegm, 3 S π k. ^ Lihua calcium strontium oxide Calcium lactate, calcium citrate or barium gluconate as a source of 1 bow ion, a B*7 carved source, and sodium phosphate or potassium phosphate as a source of phosphate ions. The source of the anion according to the invention is any halide, mineral acid or organic acid. Preferably, the source of the anion is an organic acid. Suitable inorganic acid yin 147853.doc 201221145 Ions include, but are not limited to, nitrate, sulfate, tooth ions and carbonate. Suitable organic acid anions include, but are not limited to, lactate, citrate, acetate, tartrate, maleate, succinate, pyruvate, glycolate, glutarate, malonate, and ortho-benzene Diformate. Preferred examples of the dual anion-containing calcium phosphate compound include, but are not limited to, calcium lactate phosphate, calcium citrate phosphate, calcium sulfate sulfate, and calcium maleate. The calcium phosphate compound which is optimally double anion is a calcium lactate phosphate having the following formula: Ca9L12P2, and has a Ca/P ratio of about 4.5. Lactic acid Calcium phosphate forms an octahedral structure in which tricalcium phosphate is located at the center of the structure and lactate-about-lactate is located at the apex of the structure. As mentioned above, the solubility of the anionic acid-containing compound is increased. For example, the solubility of glycerol phosphate feed and lactoic acid for teeth remineralization is known in the art as 2.0 g per 100 ml water and 0 3-1.0 g per 1 〇〇mi water, while milk The solubility of the calcium phosphate is 3. 丨 to 丨丨丨g per 1 ml of water. In another aspect, the invention provides a dental care composition comprising a dual anion-containing calcium phosphate compound of the invention and an additional orally acceptable carrier. In preparing the compositions of the present invention, one or more aqueous carriers are required to be added to the compositions. Such materials are well known in the art and are readily selected by those skilled in the art based on the physical and aesthetic characteristics desired for the compositions to be prepared. These carriers may not interfere with or inhibit the level of action of the anion-containing acid-filling mom compound of the present invention. The aqueous carrier will generally comprise from about 5% to about 99%, preferably from about 98% by weight and more preferably from about 80% to about 95% by weight of the smear. 147853.doc • 10- 201221145 The compositions of the present invention may contain a buffer. Buffer as used herein refers to an agent that can be used to adjust the pH of the composition to a range of from about pH 4 to about pH 10. The pH of the slurry of the dental care composition containing the polymeric mineral surfactant is typically from about 4 to about 1 Torr', preferably from about 4.5 to about 8, and more preferably from about 5.5 to about 7. Buffering agents include metal hydroxides, carbonates, sesquicarbonates, borates, silicates, phosphates, imidazoles, and mixtures thereof. Specific buffers include monosodium phosphate, trisodium phosphate, sodium hydroxide, potassium hydroxide, alkali metal carbonates, sodium carbonate, imidazole, pyrophosphate, citric acid, and sodium citrate. The buffering agent is used in an amount of from about 0.1% to about 55%, preferably from about 1% to about 3% or from about 1% to about 1%, and more preferably from about 1.5% to about 3, by weight of the composition of the present invention. % » The compositions of the present invention may optionally contain a calculus inhibitor such as calcium lactate 'calcium lactate, a double salt of calcium lactate and mixtures thereof, gamma _ glutamic acid PGA), pyrophosphate and other polylysine salts. Among them, coke salt is the most well-known for dental care products. Pyrophosphate can be used as a calculus inhibitor or buffer in the present invention. The coke-based S-salt salts suitable for use in the compositions of the present invention include an alkali metal pyrophosphate, a tetra alkali metal pyrophosphate, and mixtures thereof in the form of unhydrated alpha and hydrated forms of dibenzodiazepine, pyroic acid Pins and tetrapotassium pyrophosphate are preferred. f^ Other alternatives (tetra) acid salt use or a combination of penic acid fillet inhibitors include known materials such as synthetic anionic polymers. Abrasive polishing materials can also be incorporated into the dental care composition. The abrasive polishing material in the composition of the invention may be a substance that does not excessively grind dentin. The abrasive polishing material should be formulated in a dental care composition in a manner that does not impair the stability of any of the ingredients, especially the source of the gas and the polyphosphate containing the polymerization agent. Typical abrasive polishing materials include silica gel and precipitates; alumina; phosphates include orthophosphates, polymetaphosphates, and pyrofills; and mixtures thereof. Specific examples include dicalcium dihydrate normal acid dicalcium phosphate, calcium pyrophosphate, tricalcium carbonate, calcium polyvinyl silicate, insoluble sodium polymetaphosphate, hydrated alumina, beta pyrophosphate, calcium carbonate, resin abrasives such as urea A particulate condensation product with ruthenium and other abrasive polishing materials such as those disclosed in U.S. Patent No. 3,070,510. Mixtures of abrasives can also be used. Compositions of the invention may include tooth whiteners or bleaches. Suitable active agents for whitening are selected from the group consisting of peroxides, metal sulfites, perborates, percarbonates, peroxyacids, peroxysulfates, and combinations thereof. Suitable peroxide compounds include hydrazine peroxide, calcium peroxide (Ca〇2, Calcium per〇xide), and carbonamide peroxide (carbamide peroxide' is a type of carbamide peroxide (Urea per 〇xide) and mixtures thereof. Suitable metal sulfites include calcium chlorite, bismuth sulphate, magnesium sulfite, lithium chlorite, sodium sulfite and potassium sulfite. Other whitening active agents It may be hypochlorite and sulfur dioxide. The preferred gas sulfite is sodium sulfite. Preferably, the percarbonate is sodium percarbonate. Preferably, the peroxysulfate is potassium hydrogen persulfate. The composition of the present invention may It contains from about 0.01% to about 1% by weight, preferably from about 0.1% to about 5%, more preferably from about 2% to about 3%, and most preferably from about 0.3% to about 3% by weight of the composition of the present invention. 8%.8% tooth whitening active agent. The present invention provides toothpaste, dentifrice, tooth powder, topical oral gel, mouthwash, denture product, oral spray, buccal ingot, chewable oral ingot 147853.doc •12·201221145 Compositions of the agent, chewing gum form, dental patch. These compositions have always contained some thickening substances or Mixtures to provide a desirable consistency. Preferred thickeners are carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose, and water soluble salts of cellulose ethers (such as sodium carboxymethyl cellulose and hydroxyethyl cellulose) Sodium). Natural rubbers such as gum karaya, gumsan gum, gum arabic and tragacanth can also be used. Colloidal magnesium aluminum silicate or fine powdered cerium oxide can be used as an increase. A portion of the thickening agent is used to further improve the texture. The thickening agent may be used in an amount of from about 1% by weight to about 15% by weight of the composition of the invention. It is a humectant. The humectant is used to prevent the toothpaste composition from hardening after exposure to air, and some humectants can also impart a desirable sweetness to the toothpaste composition. The humectant suitable for use in the present invention includes glycerin, sorbitol, Polyethylene glycol, propylene glycol, and other edible polyols. The compositions of the present invention may also comprise a surfactant, also commonly referred to as a sudsmg agent. Suitable surfactants are within a wide range of values. Quite stable A foaming surfactant. The surfactant may be an anionic surfactant, a nonionic surfactant, an amphoteric surfactant, a zwitterionic surfactant, a cationic surfactant or a mixture thereof. Incorporating the compositions of the present invention, examples of which are coloring or whitening agents, preservatives, polyoxygen, chlorophyll compounds, and amides such as urea, diammonium phosphate, and mixtures thereof. Such adjuvants can substantially affect The amount of characteristics and characteristics is in the human composition 'and the amount is considered to be involved. I47853.doc -13- 201221145 The type of the special preparation is appropriately selected. Agents for some (four) 'may require that the composition of the present invention include antibacterial compounds, flavoring or sweetening materials can be used to formulate the composition of the present invention. Examples of flavoring components include flavoring oils (eg, spearmint) Oil, pepper thin oil, wintergreen oil, sassafras oil, clove oil, sage oil according to tree oil, marjoram oil, cinnamon oil, lemon oil and oil) and salicylate. Suitable sweeteners include sucrose, lactose, maltose, sorbitol, sodium cyclohexyl sulfonate and saccharin. Suitable flavoring agents and sweeteners may together comprise from about 0.1% to about 5% or more of the composition. The dual anion-containing calcium phosphate compound or composition of the present invention may be, but not limited to, tooth f, tooth powder, dentifrice, mouthwash, mousse, denture product, topical oral gel, oral lozenge, oral bond , sugar coating, chewing gum and dental patches in the form of applications. In one embodiment, the dual anion-containing calcium phosphate compound of the present invention, or <s> sigma, can be used for remineralization in the form of a dental patch. According to a consistent embodiment of the present invention, a patch for remineralization of teeth comprises a dental adhesive layer and a support layer comprising the calcium phosphate compound or composition containing an anion of the present invention. In another embodiment of the invention, the patch may further comprise one or more layers comprising one or more dental active ingredients. Those skilled in the art can determine the number of layers based on the application of the patch. The adhesive layer of the teeth releases calcium ions and the S root anion after adhering to the tooth surface and has hydrophilic properties and a good adhesion strength. In accordance with an embodiment of the present invention, in addition to the anionic calcium phosphate compound or composition of the present invention, the dental adhesive layer also comprises one or more teeth 147853.doc 201221145 active ingredient. According to the invention, a support layer is known in the art and comprises a substance which is insoluble in water. Examples of the water-insoluble substance include, but are not limited to, light-resistant paper, cellulose acetate phthalate, polyvinyl acetate, ethyl cellulose, polymethyl methacrylate, methacrylic acid ethyl methacrylate Betaine/mercaptopropionic acid S copolymer (which is commercially available under the trademark Yukaformer manufactured by Mitsubishi), methacrylic acid copolymer (such as Eudragit L 100, Eudragit L 125, Eudragit L 100-55, Eudragit L 30D) -55), mercaptopropionamide-based glycerin copolymer (such as Eudragit E 1 00, Eudragit E 125, Eudragit RL 100, Eudragit RL 30D) or a mixture thereof. In addition to the dual anion-containing calcium phosphate compound or composition of the present invention, the dental adhesive layer of the patch may contain a hydrophilic polymer. According to the invention, the polymer may be, but is not limited to, a polyalkyl vinyl ether-maleic acid copolymer (PVM/MA copolymer) such as Gantrez AN 119, AN 139 and S-97; polyethylene glycol Polyacrylic acid; Poloxamer 407 (Pluronic) Pluronic F127; Polyethylene. Bilo alpha ketone-ethylene acetate copolymer (PVP / VA copolymer), such as Luviskol VA and Plasdone S PVP / VA; polyoxyethylene (Polyox); polyvinylpyrrolidone (PVP, K-15. about.K-120); Polyquaterium-ll (Gafquat 755N); Polyquaternium-39 (Merquat plus 3330); Carboxy Carboxol; Hydroxypropylmethylcellulose Hydroxyethyl cellulose; propyl cellulose; gel; gelatin; and alginate, such as sodium alginate. The above polymers may be used singly or in combination. Polyvinylpyrrolidone (PVP) is the most preferred hydrophilic polymer. Solvents for such polymers include water, ethanol or a mixture thereof 147853.doc -15-201221145. Further, other organic solvents such as ethyl acetate, dichloromethane, isopropanol, acetonitrile or a mixture thereof in various ratios may also be used as the solvent. The patch to be attached to the tooth should be flexible enough to deform it to conform to the contours of the tooth. Due to the poor flexibility of some polymers, suitable plasticizers can be added. Polypropylene glycol, glycerin and polyethylene I are used as plasticizers. The patch of the present invention may further comprise a whitening agent for whitening the teeth, a fluoride ion for preventing scaly teeth or a stannous ion for reducing gingivitis or plaque. The patch of the present invention may further comprise a pigment having various colors, a flavoring agent, a sweetener, and a wetting agent. Pigments are used to make teeth whiter and are selected from the group consisting of titanium dioxide, talc, oxyhydrogen (tetra) gray stone, zinc oxide and mixtures thereof. Examples of flavoring agents include peppermint, spearmint, wintergreen, sage, eucalyptus oil, methyl salicylate and other fruit extracts. Examples of sweeteners and wetting agents include mannitol, xylitol, lactose, aspartame and sodium saccharin. EXAMPLES Example 1 Preparation of Lactic Acid Calcium Phosphate with High Solubility 0.85 g of calcium oxide (Ca〇), 2.81 g of lactic acid and 〇12 g of disc acid were mixed in 96 22 g of deionized water. The resulting mixture was filtered and dried to form a powder of lactic acid phosphonium calcium compound. The calcium lactate phosphate compound had an irregular molecular structure and low crystallinity and high solubility due to the addition of lactate. In addition, the lactic acid phosphorus-compound is relatively in water, so no phase transition will occur. Therefore, calcium ions and phosphate ions can be released from the calcium lactate phosphate compound to maintain and promote effective tooth remineralization. The structure of the calcium lactate phosphate compound was measured by χ-ray around N7853.doc -16-201221145 (XRD), and its xRD diffraction pattern is shown in Fig. 1. The solubility of the calcium lactate phosphate compound is 3.1-11.1 g per 1 〇〇 ml H20. Example 2 The remineralized patch of the present invention and the remineralization test The patch of the present invention comprises a tooth adhesion layer and a support layer. The dental adhesive layer of the patch comprises 1.5 wt% poly-γ_glutamic acid (γ-PGA), 2.5 wt% glycerol, 3 wt% of the calcium lactate phosphate compound of the invention, and 10 wt% polyvinylpyrrolidone (PVP). And 83 wt% deionized water. The support layer of the patch comprises 2 〇 wt% ethyl cellulose, 10 wt% glycerol and 7 〇 wt% ethanol. The remineralized patch of the present invention was placed at 37 ° C and 1 〇〇 0 /. Simulation of Humidity The oral environment is used to assess whether the calcium lactate clusters in the patch are stable in a warm and humid oral environment. As shown in the XRD diffraction pattern of Fig. 2, the XRD profiles of the calcium lactate clusters remained the same at the third, third, i, and ninth days, so that no phase transition occurred in the calcium lactate cluster. The patch maintains favorable stability during use. The inventive patch containing 2 wt% and 3 wt% calcium lactate, deionized water as a blank control, artificial saliva as a positive control, and amorphous calcium phosphate (ACP)/water (W) and γ-poly glutamine Acid (y_pGA)_Acp/water (w) was used as a comparative example to evaluate the remineralization of the patch. By using i M acetic acid to invade the tooth is (the surface was attached to the teeth for re-mineralization for 3 minutes, and then the Knoop microhardness of the tooth was measured with a microhardness tester (Nupper hardness, KHN) to verify the effectiveness of remineralized patches. The remineralization system measures the percentage of microhardness recovery of teeth: 147853.doc -17- 201221145 Remineralization of teeth occurs within 15 to 30 minutes after patching The correlation between microhardness recovery (%) and treatment time is shown in the following table: Deionized water artificial saliva 2% CLP patch 3% CLP patch ACP/W γ-PGA-ACP/W 0 minutes 0.0 0.0 0.0 0.0 0.0 0.0 15 minutes 24.7 7.9 16.6 57.5 3.4 7.2 30 minutes 23.7 10.6 37.7 66.2 0.6 10.1 3 days 17.3 23.1 45.1 78.7 13.0 51.9 The results in the above table are shown in Figure 3. As shown in Figure 3, with 2% CLP or 3% The patch of CLP provides advantageous remineralization. The teeth after treatment with the patch of the present invention are examined under the microscope for 〇 minute, 2 days, 2 days, 23 hours 30 minutes, and 2 days and 23 hours 45 minutes. As shown in the figure, the marks left in the teeth due to the measurement of the microhardness become more and more over time. The results show that the patch of the present invention has the function of repairing teeth.Example 3 The solubility and remineralization test of other high solubility complexes of the present invention use calcium carbonate, calcium sulfate, calcium hydroxide or calcium citrate, citric acid , acetic acid, lactic acid or maleic acid and phosphate form a calcium-anionic phosphate complex powder, and the solubility of the calcium lactate complex is determined according to the method mentioned in Example 1. The solubility of the resulting complex is higher than that per iOO Ml H20 3.0 g ° In the remineralization assay, the calcium-anionic phosphate complex was prepared into a patch and the microhardness recovery percentage of the obtained patch was determined according to the method of Example 2. The resulting patch hardness recovery percentage was 15 minutes. , after 30 minutes and 3 days, respectively, higher than 50%, 60% and 70%. [Simplified illustration] 147853.doc -18- 201221145 Figure 1 shows the x-ray diffraction pattern of the calcium lactate phosphate of the present invention (xrd Figure 2 shows the XRD data of calcium lactate phosphate placed in simulated oral environment for minutes, minutes, 1 day and 9 days. Figure 3 shows the correlation between the percentage of microhardness recovery (%) of CLP patch and treatment time. The symbol "◊" indicates deionized water, the symbol "α" indicates artificial saliva, the symbol "△" indicates 2〇/〇 CLP patch and the symbol "χ" indicates 3% CLP patch. Figure 4 shows the use of the present invention. Photographs of the marks recovered from the microhardness measurement in the teeth after patch treatment. 147853.doc