研發以明膠為模版之中孔洞鈣矽材料應用於治療牙本質過敏症

Development of Gelatin-templated Mesoporous Calcium Silicate Biomaterials for the Treatment of Dentin Hypersensitivity

鄭雅文(Ya-Wen Cheng)

指導教授 ： 林俊彬

國立臺灣大學/牙醫專業學院/臨床牙醫學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.10521

摘要

對許多牙科執業醫師而言，牙本質過敏症是很常見的主訴，卻也是很棘手的難題。目前市面上有許多號稱能有效緩解牙齒敏感症狀的商品，但卻沒有任何產品能立即而持久的療效。本團隊所研發之第一代含氧化鈣中孔洞二氧化矽材料，已被證實能有效進入牙本質小管內，產生深達100μm的結晶，且使用液體流動模組測試牙本質通透性，發現其可將牙本質滲透性降低至19.1%。但在綠色化學觀念抬頭的二十一世紀，以更環保的方法製造有效材料，是本團隊努力的方向。除此之外，本團隊更進一步探討以中孔洞鈣矽材料治療牙本質過敏症的優勢，並評估其在活體的效用性與生物相容性。本實驗主要分成三個部分，首先，本團隊先合成以明膠為模版之中孔洞鈣矽材料，將其與不同體積之30%磷酸混和，探討在不同pH值下的製劑對牙本質小管的封閉情形，發現當製劑pH值在5.0~5.5時，能在不酸蝕牙本質結構的情形下，在牙本質小管內產生深達30μm以上的結晶。第二部分，則以鈣離子釋放量以及碳酸鈣與中孔洞二氧化矽混和方式，探討以中孔洞鈣矽材料治療牙本質過敏症的優勢。實驗結果發現，將碳酸鈣含浸於二氧化矽顆粒的孔洞內，與磷酸溶液混和後才能產生過飽和的鈣離子與磷酸根離子溶液，且中孔洞二氧化矽顆粒能扮演反應槽的角色吸附酸液，並扮演結晶的起始點，使得此製劑相較於碳酸鈣/30%磷酸製劑與碳酸鈣/中孔洞二氧化矽/30%磷酸製劑，能更有效且不破壞牙本質結構的情形下，封閉牙本質小管。第三部分，則進行動物實驗以評估此製劑在活體的效用性與對牙髓組織的刺激性。在電子顯微鏡觀察下，發現本製劑在活體內有牙髓腔靜水壓存在下，仍可在牙本質小管內產生超過30μm的結晶。而比較中孔洞鈣矽材料/30%磷酸製劑與市售產品Seal and Protect與負對照組IRM對牙髓組織的刺激性，發現三者並無統計上顯著差異。
結論：(1) 中孔洞鈣矽材料/30%磷酸製劑在pH 5.0~5.5時，能在不酸蝕牙本質的情形下有效封閉牙本質小管。(2) 將碳酸鈣含浸於二氧化矽顆粒的孔洞內，與磷酸溶液混和後才能產生過飽和的鈣離子與磷酸根離子溶液，在不破壞牙本質的情形下有效封閉牙本質小管。(3)在動物實驗中證實，本製劑在活體內仍內有效封閉牙本質小管，且對牙髓組織無顯著刺激性。

關鍵字

中孔洞 ； 牙本質過敏症 ； 動物實驗 ； 牙髓刺激性測試 ； 過飽和鈣離子與磷酸根離子溶液

並列摘要

Dentin hypersensitivity is a common encountered chief complaint for dental general practitioner, but it is also a troublesome issue. There are various kinds of commercial products which claim to be able to relieve the symptoms of dentin hypersensitivity, but none of the products have immediate and long-lasting effects. The first generation of CaO@mesoporous silica developed by our group was proved to be effective in occlusion of the dentinal tubules with recrystallized precipitants penetrating into the tubules as deep as 100 μm. Also, after application of Cao@mesoporous silica paste mixing with 30% phosphoric acid, the permeability of dentin disc decreased to 19.1% when evaluated by fluid flow model.
With the advocation of green chemistry in the 21st century, it is our goal to develop efficient materials in a more environmentally friendly way. In addition, we also tried to investigate the advantages using mesoporous calcium silicate materials for the treatment of dentin hypersensitivity, and evaluate its in vivo efficacy and biocompatibility. This research comprised of three parts. First, we developed the gelatin-templated calcium silicate material, and mixing it with different volumes of 30% phosphoric acid, and evaluate the efficacy of occlusion of dentinal tubules by using pastes with different pH value. The results showed that by using pastes with the pH value between 5.0~5.5, the dentinal tubules could be occluded by precipitates as deep as 30μm without eroding the dentin. The second part investigated the advantages of mesoporous calcium silicate material by measuring calcium ion concentration and evaluation the efficacy by mixing calcium carbonate and mesoporous silica in different ways. The results revealed that only by impregnating calcium carbonate in the nano pores of mesoporous silica could the paste be hypersaturated with calcium ions and phosphate ions. Also, the mesoporous silica played the role of acid adsorption and the starting point of nucleation, which enabled the paste occlude the dentinal tubules efficiently without eroding the dentin. In the third part, we evaluated the in vivo efficacy and biocompatibility of the desensitizing paste. Under SEM observation, we found precipitates penetrated more than 30μm despite the presence of pulpal hydrostatic pressure. As to the pulp irritation, we found that there were no significant differences among our desensitizing paste, commercial products Seal Protect, and the negative control IRM.
In conclusion：(1) Mesoporous calcium silicate material mixing with 30% phosphoric acid could effectively occlude the dentinal tubules without eroding the dentin. (2) Only by impregnating calcium carbonate in the nano pores of mesoporous silica could the paste be hypersaturated with calcium ions and phosphate ions, which enabled the dentinal tubules be occluded without being eroded. (3) Animal study demonstrated that the paste could effectively occlude the dentinal tubules in vivo without irritating the pulp.

並列關鍵字

Mesoporous ； dentin hypersensitivity ； animal study ； pulp irritation test ； hypersaturated calcium and phosphate solution

參考文獻

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