201021858 六、發明說明： 【發明所屬之技術領域】 本發明係有關於-種水膠敷料及其製備方法，特別是有 關於一種促骨生成之水勝敷料及其製備方法。 【先前技術】 水膠（hydrogel)係、-具有親水官能基之吸水性材料，在 水性環境下可吸收水分以增加其體積，且能維持其三維結 構。水膠的結構中包含·親水端與—疏水端，藉由親水端與 水形成水合物，並且利用疏水端不與水分子鍵結以^成水 膠。其中，其親水性官能基可為羥基(_〇H)、羧基( c〇〇H)或 酰胺基(<〇]^112)等。再者’水膠的含水量與其形成方式有關， 形成方式可區分為化學性及物理性；化學性是利用共價鍵鍵 結形成凝膠，而物理性形成方式包含利用pH值變化、離子 交聯、溫度變化、溶劑交換或結晶。 關於水膠在生醫方面應用，因為水膠材料本身具有良好 的流動性可塑造成各種形狀；此外’水膠可作為藥物釋放、 細胞及生長因子的載體，其形成方式僅需與水膠混合攪拌即 可。如美國專利 7,381，716 (H.-W. Sung, Y._H. Lin H Tu “Nanoparticles for protein drug delivery’’，2008 )係提出一 蛋白質藥物輸送之奈米顆粒’其包含一幾丁聚醣（chit〇san) 殼艘、一聚麵胺酸（poly-glutamic acid)水膠，並且表面具 有正電荷活性物以增加其滲透性。 3 201021858 另外，將水膠移入體内僅需用利用注射的方式，不需做 侵入性的手術。近年來，將水膠用於骨科填補材料如：Pepgen P-15 Flow®。而應用於牙科的水膠敷料如：Aftach®和 Orabase®。 一般而言，止血敷料需包含生物相容性、生物可吸收性、 高止血率的特點。有關上述之拔牙傷口敷料以及引導骨再生 技術，目前正在被使用中，但臨床上的表現仍未滿意。有鑑 於此，仍有必要發展新的敷料，具有止血作用外，且在傷口 上可以被人體分解，以促進引導骨再生或牙科膺復物的放置 (人工植牙），係亟欲發展之技術。 【發明内容】 鑒於上述之發明背景中，為了符合產業上之要求，本發 明提供一種新的促骨生成之水膠敷料及其形成方法。 本發明揭露了一種促骨生成之水膠敷料，其包含一幾丁 聚聽（Chitosan)與一聚麵胺酸(γ-Polyglutamate)，其中，該幾 丁聚醣與該聚麩胺酸係藉由氨基與酸基錯合物形成該促骨生 成之水膠敷料。 本發明所揭露之促骨生成之水膠本身帶有良好的流動性 能可塑造成不同的形狀以更好應用於高曲度的區域（拔牙 4 201021858 窩）。此外，幾丁聚醣（Chitosan)混摻聚麩胺酸(Y_p〇lyglutamat^ 後幾丁聚聽（Chitosan)降解速度較僅使用幾丁聚糖（chit〇san sponge)快，且聚楚胺酸(γ-Polygiutamate)具促骨生長的能力。 因此，本發明所揭露之促骨生成之水膠對於傷口癒合與骨生 成較僅使用幾丁聚醣(Chitosan)有加成的作用。 【實施方式】 e 本發明在此揭示一種促骨生成之水膠敷料。為了能徹底 地瞭解本發明’將在下列的描述中提出詳盡的步称及其組 成。顯然地，本發明的施行並未限定於該領域之技藝者所熟 習的特殊細節。另一方面，眾所周知的組成或步驟並未描述 於細節中，以避免造成本發明不必要之限制。本發明的較佳 實施例會詳細描述如下’然而除了這些詳細描述之外，本發 明還可以廣泛地施行在其他的實施例中，且本發明的範圍不 受限定，其以之後的專利範圍為準。 本發明之一第一實施例揭露一種促骨生成之水膠敷料 (hydrogel dressing)，水膠敷料包含一幾 丁聚醣(chit〇san)與一 聚麵胺酸(γ-Polyglutamate)’其中’幾丁聚醣與聚麵胺酸係藉 由氨基與酸基錯合物形成促骨生成之水膠敷料。其中，上述之 幾丁聚醣分子量為200至300萬’而乙醯度為百分之8〇以上， 且聚麩胺酸之分子量為1萬以上。 於本實施例之一較佳範例中，上述之水膝敷料中之幾丁聚 餹與聚麩胺酸（chitosan/yPGA)之重量比值範圍為1/99至 5 201021858 而上述之水膠敷料較宜之酸鹼值範圍為5.5至85。 於本實施例之另-較佳範射，上述之切敷料更包含下 2族群之—者：藥物、無機材料與有機材料（可生物分解材 料）。此外，上述之水膠敷料可應科：創傷敷材、創傷復原 與藥物控制釋放材料。 本發明之-第二實施例揭露-種促骨生成之水膠敷料的 ❿ 形成方法，其包含：提供—聚制酸水溶液將聚麵胺酸水 溶液混合-幾丁聚糖與—酸性溶液，藉以形成—酸性之幾丁 聚聽/聚麵胺酸之祕水膠；㈣性之幾丁聚糖/聚麵胺酸混捧 水膝溶於-驗性溶液中，以便進行―酸驗中和反應 ，藉以形 成促骨生成之水職料1巾，於進行酸驗中和反應後更包 含乾燥程序，乾燥程序係獨立選自下列族群之一者：冷束 乾燥與加熱㈣。其巾，上述之H容液係選自下列族群之 . 者或其任意組合：醋酸、碟酸與有機酸，而上述之驗性溶 液係選自下列族群之一者或其任意組合 :氫氧化鈉、氫氧化 钾'氫氧化鎮與氫氧化詞。此外，上述之水朦敷料可具有下 列應用：創傷敷材、創傷復原與藥物控制釋放材料。 範例一 將五十隻大鼠共一百顆上顎門齒隨機挑選六十四顆拔 除，並將拔牙窩分為四組，分別為： 1_控制組：不放置任何數料，為自歸合之拔牙傷口。 2·對照組：放置止血敷料Spongostan®。 201021858 3. 试驗組（1):放置幾丁聚聽（chitosan sponge)。 4. 試驗組(2):放置幾丁聚醣與聚麵胺酸摻混之水膠敷料。 分別在四個時間點，一週，二週，四週，六週，將大鼠 犧牲。犧牲的方式是將大鼠放入充滿二氧化碳的箱子中窒息 死亡。大鼠犧牲後切取組織樣本拍攝X光片及製作組織切片。 藉由X光觀察拔除門齒六週後之拔牙窩，得知試驗組(2) 之拔牙窩鈣化程度最高，已無法分辨與周圍齒槽骨的界線（第 〇 -圖）。 並且’藉由光學顯微鏡觀察大鼠拔除門齒六週後之組織 切片；如第二圓所示，控制組之拔牙窩内有大量新生的骨小 樑（trabecular bone)從四周骨壁向牙窩中心侵入；如第三圖 所示’對照組在拔牙窩中心處有少量骨小梁形成，並在高倍 顧微鏡下可見到放射狀的骨元（osteon)及哈氏管（Haversian canal);如第四圖所示，試驗組（1)之拔牙窩大部分屬於質地 鬆散的骨小梁’骨小梁間有許多空隙，且在高倍率觀察下可 見哈氏管；如第五圊所示，試驗組(2)之拔牙窩已經被板狀構 造之新生骨佔據，為骨小梁鈣化形成緻密的皮質骨 (Cortical bcme)’高倍率觀察下可見骨元。結果顯示，幾丁聚醣與聚麩 胺酸換混之水膠敷料相較於幾丁聚醣對於傷口癒合與骨生成 有更好的效果。 顯然地，依照上面實施例中的描述，本發明可能有許多 的修正與差異。因此需要在其附加的權利要求項之範圍内加 201021858 以理解，除了上述詳細的描述外，本發明還可以廣泛地在其 他的實施例中施行。上述僅為本發明之較佳實施例而已，並 非用以限定本發明之申請專利範圍；凡其它未脫離本發明所 揭示之精神下所完成的等效改變或修飾，均應包含在下述申 請專利範圍内。 201021858 【圖式簡單說明】 第一圖係為根據本發明範例一，大鼠拔除門齒六週後之拔牙 窩，並放置幾丁聚醣與聚麩胺酸摻混之水膠敷料（試驗組(2)) 之X光照片； 第二圖係為根據本發明範例一，大鼠拔除門齒六週後之拔牙 窩，不放置任何敷料（控制組）之光學顯微鏡照片； ❿ 第三圖係為根據本發明範例一，大鼠拔除門齒六週後之拔牙 窩，並放置止血敷料Spongostan® (對照組）之光學顯微鏡 照片； 第四圖係為根據本發明範例一，大鼠拔除門齒六週後之拔牙 窩，並放置幾丁聚聽（Chitosan sponge，試驗組（1))之光學 顯微鏡照片；以及 第五圖係為根據本發明範例一，大鼠拔除門齒六週後之拔牙 窩，並放置幾丁聚醣與聚麩胺酸摻混之水膠敷料。 (試驗組(2))之光學顯微鏡照片。 9201021858 VI. Description of the Invention: [Technical Field] The present invention relates to a water-based rubber dressing and a preparation method thereof, and more particularly to a water-splitting dressing for promoting bone formation and a preparation method thereof. [Prior Art] Hydrogel, a water-absorbent material having a hydrophilic functional group, absorbs moisture in an aqueous environment to increase its volume and maintain its three-dimensional structure. The structure of the water gel comprises a hydrophilic end and a hydrophobic end, which form a hydrate with water by a hydrophilic end, and are not bonded to water molecules by a hydrophobic end to form a hydrogel. Here, the hydrophilic functional group may be a hydroxyl group (-〇H), a carboxyl group (c〇〇H) or an amide group (<〇)^112). Furthermore, the water content of 'water gel is related to its formation mode. The formation method can be divided into chemical and physical; chemical is the formation of gel by covalent bond bonding, and the physical formation method includes pH change and ion exchange. Coupling, temperature change, solvent exchange or crystallization. Regarding the application of water gel in biomedicine, because the water gel material itself has good fluidity, it can be molded into various shapes; in addition, 'water gel can be used as a carrier for drug release, cell and growth factor, and its formation method only needs to be mixed with water gel. Just fine. For example, U.S. Patent 7,381,716 (H.-W. Sung, Y._H. Lin H Tu "Nanoparticles for protein drug delivery"', 2008) proposes a protein drug delivery nanoparticle "which contains a chitosan (chit〇san) shell, poly-glutamic acid water gel, and has a positively charged active on the surface to increase its permeability. 3 201021858 In addition, the injection of water gel into the body only requires the use of injection In this way, there is no need for invasive surgery. In recent years, water gel has been used in orthopedic filling materials such as Pepgen P-15 Flow®, while hydrogel dressings for dentistry such as: Aftach® and Orabase®. The hemostatic dressing needs to include biocompatibility, bioabsorbability, and high hemostatic rate. The above-mentioned tooth extraction wound dressing and guided bone regeneration technology are currently being used, but the clinical performance is still not satisfactory. Therefore, it is still necessary to develop a new dressing, which has a hemostatic effect and can be decomposed by the human body on the wound to promote guiding bone regeneration or placement of dental sputum complex (artificial implant), which is a technique for development. SUMMARY OF THE INVENTION In view of the above-described background of the invention, in order to meet the requirements of the industry, the present invention provides a novel bone-promoting hydrogel dressing and a method for forming the same. The present invention discloses an osteogenic dressing for water-promoting, which The invention comprises Chitosan and γ-Polyglutamate, wherein the chitosan and the polyglutamic acid form the osteogenic formation by an amino group and an acid group complex. Hydrogel dressing. The bone-promoting water gel disclosed in the present invention has good flow properties and can be molded into different shapes to be better applied to a region of high curvature (extraction 4 201021858 nest). In addition, chitosan (Chitosan) mixed with glutamic acid (Y_p〇lyglutamat^) Chitosan degradation rate is faster than using only chitin (chit〇san sponge), and polyglycolic acid (γ-Polygiutamate) The ability to promote bone growth. Therefore, the osteogenic gel of the present invention has an additive effect on wound healing and bone formation using only chitosan. Reveal an osteogenic In order to be able to fully understand the present invention, detailed steps and compositions thereof will be set forth in the following description. It is obvious that the present invention is not limited to the specific details familiar to those skilled in the art. On the other hand, well-known components or steps are not described in detail to avoid unnecessarily limiting the present invention. The preferred embodiments of the present invention will be described in detail below. However, the present invention may be broadly described in addition to the detailed description. The scope of the present invention is not limited by the scope of the invention, which is subject to the scope of the following patents. A first embodiment of the present invention discloses an osteogenic hydrogel dressing comprising a chitosan and a gamma-polyglutamate. Chitosan and poly-glycolic acid form an osteogenesis-producing hydrogel dressing by an amino group and an acid-based complex. The chitosan has a molecular weight of 200 to 3 million ' and an oxime degree of 8 % or more, and the molecular weight of the polyglutamic acid is 10,000 or more. In a preferred embodiment of the present embodiment, the weight ratio of the chitosan to the glutamic acid (chitosan/yPGA) in the above-mentioned water knee dressing ranges from 1/99 to 5 201021858, and the above-mentioned water gel dressing is more Suitable pH ranges from 5.5 to 85. In another preferred embodiment of the present embodiment, the above cut dressing further comprises the following two groups: a drug, an inorganic material and an organic material (biodegradable material). In addition, the above-mentioned hydrogel dressings can be applied to: wound dressings, wound healing and drug controlled release materials. The second embodiment of the present invention discloses a method for forming a hydrazine-forming hydrogel dressing comprising: providing a poly-acid aqueous solution to mix a polyglycolic acid aqueous solution with a chitosan and an acidic solution, thereby Forming - the acidity of the chitosan/polyglycolic acid secret water gel; (4) the chitosan/polyglycolic acid mixed with the water knee in the -testing solution for the acid test neutralization reaction In order to form a water-promoting material 1 towel, after the acid test and the reaction, the drying process is further included, and the drying process is independently selected from one of the following groups: cold beam drying and heating (4). The towel, the above H liquid is selected from the following groups: or any combination thereof: acetic acid, dish acid and organic acid, and the above-mentioned test solution is selected from one of the following groups or any combination thereof: hydroxide Sodium, potassium hydroxide 'hydrogenation town and hydroxide word. In addition, the above-described leech dressings may have the following applications: wound dressings, wound healing, and drug controlled release materials. In the first example, a total of 100 upper incisors were randomly selected from fifty rats and sixty-four were removed. The extraction sockets were divided into four groups: 1_ control group: no material was placed, self-retribution Tooth extraction wound. 2. Control group: Place the hemostatic dressing Spongostan®. 201021858 3. Test group (1): Place chitosan sponge. 4. Test group (2): Place a water gel dressing blended with chitosan and polyglycolic acid. Rats were sacrificed at four time points, one week, two weeks, four weeks, and six weeks. The way to sacrifice is to suffocate the rat into a box filled with carbon dioxide and die. After the sacrifice, the tissue samples were taken to take X-ray films and tissue sections were made. The extraction of the incisors after 6 weeks of removal of the incisors by X-ray observation revealed that the extraction socket of the test group (2) had the highest degree of calcification and could not distinguish the boundary with the surrounding alveolar bone (Fig. And 'review the tissue section of the rat after 6 weeks of removal of the incisors by light microscopy; as shown in the second circle, there are a large number of new trabecular bones in the extraction socket of the control group from the surrounding bone wall to the center of the socket. Invasion; as shown in the third figure, the control group has a small amount of trabecular bone formation at the center of the extraction socket, and radial osteon and Havesian canal are visible under high magnification micromirrors; As shown in the fourth figure, most of the extraction sockets of the experimental group (1) belong to the loose trabecular bone. There are many gaps between the trabecular bones, and the Hastelloy tube can be seen under high magnification observation; as shown in the fifth ,, the test The extraction socket of group (2) has been occupied by the new bone of the plate-like structure, forming a compact cortical bone (Cortical bcme) for trabecular calcification. The bone is visible under high magnification. The results show that the water-gel dressing of chitosan and polyglutamate has a better effect on wound healing and bone formation than chitosan. Obviously, many modifications and differences may be made to the invention in light of the above description. Therefore, it is to be understood that the present invention may be practiced in other embodiments in addition to the above detailed description. The above are only the preferred embodiments of the present invention, and are not intended to limit the scope of the claims of the present invention; all other equivalent changes or modifications which are not departing from the spirit of the present invention should be included in the following claims. Within the scope. 201021858 [Simplified description of the drawings] The first figure is based on the first example of the present invention, the extraction socket of the rat after six weeks of removal of the incisors, and the placement of chitosan and polyglutamic acid mixed water gel dressing (test group ( 2)) X-ray photograph; the second diagram is an optical micrograph of the extraction socket after the rat has been removed for six weeks, without placing any dressing (control group) according to the first example of the present invention; Example 1 of the present invention, the extraction socket of the rat after 6 weeks of removal of the incisors, and the optical micrograph of the hemostatic dressing Spongostan® (control group); the fourth figure is according to the first example of the present invention, after the rat has removed the incisors for six weeks. The dental fossa was extracted, and an optical microscope photograph of Chitosan sponge (test group (1)) was placed; and the fifth figure was the extraction socket according to the first example of the present invention, after the rat was removed for six weeks, and placed a few A water gel dressing blended with butan and polyglutamic acid. (Photomicrograph of the test group (2)). 9