1322839 九、發明說明： .【發明所屬之技術領域】 本發明是有關於一種不織右制 +辦听之製備方法，且特別是關 於一種止血不織布的製備方法及其應用。 【先前技術】 膠原蛋白（collagen)為-種動物性高分子，當血管壁^ 損後，膠原蛋白會立刻與血小板膜膽蛋白結合，進而㈣ 血小板黏附於傷口上，以形成血栓，達到止血的功能。 儘管膠原蛋白已逐漸地應用在止血敷料上，但由於肩 生物分解性極佳’於實際應用時會有分解過快等缺點。区 此多將料酸鈉與膠原蛋白複合，J^乾技術製造成多孔 體或稱海綿體（sp〇nge)的形式，強化其機械性。然而，此種 多孔體止血材，其吸液速度較慢，因此容易產生回渗現象， 無法使傷口保持乾燥，易造成感染。 :管市面上尚有其他種類之止▲敷料，但亦有諸多缺 二寺改善。舉例而言，以海藻酸鹽所製成的海藻片，其 '4為天然植物性高分子，故與動物細胞之生物相容性有 :加強nx氧化纖維素所製成的止血紗布，則是無 夕促進凝血，以㈣時間内迅速達到止血功效。 1322839 因此’仍待開發-種新的止血材’除了具有良好的生 物相容性外，並能提供較佳之吸液速度，㈣可促進凝血 速度，以保持傷口乾燥。 【發明内容】 因此本發明的目的之一就是在提供一種止血不織布， 用以提供較佳之吸液性，並促進凝血速度。 根據本發明之上述目的，提出一種止血不織布的製備方 法。首先，分別配製紡絲原液及金屬鹽成型液，其令紡絲 原液包含鹼金族海藻酸鹽、膠原蛋白與白芨。接著，進疒 濕式紡絲，使上述之紡絲原液及金屬鹽成型液形成複合纖 維。然後利用交聯劑使複合纖維交聯聚合，最後，將交聯 聚合後的複合纖維製成不織布。 本發明的另一目的，則是提出一種止血不織布，此不織 布至少包含複數個複合纖維。該些複合纖維除了交聯成型 外’其成分包含海藻酸鈣、白芨以及膠原蛋白，其中膠原 蛋白、白芨與海藻酸鈣係均勻混合，其中鹼土族海藻酸鹽 與膠原蛋白之混合重量比係為1:9-9:1，而白芨之重量係為 驗土族海藻酸鹽與膠原蛋白重量總和之0.01-1.0%。 與傳統止血敷料相較，上述之止血不織布除了具有較佳 之血液吸附性外，亦可於短時間内達到凝血致果，有助於 傷口癒合。 【實施方式】 於本發明之一實施例中，係提出一種止血不織布之製 備方法’並於製備的過程中，加入膠原蛋白與常用之中藥 -白丄以增進其生物相容性，並促進凝血 逮度。 請參照第1圖，其係繪示本發明一實施例中，止血不 織布的製備概略流程。首先，配製含有鹼金族海藻酸鹽、 白复與膠原蛋白之紡絲原液（步驟1G2)e另外，配製金屬鹽 成型液（步驟1G4)。然後’進行濕式纺絲，使紡絲原液及金 屬鹽成型液形成複合纖維(步驟1〇6)。接著，將複合纖维产 泡於交聯劑中，則吏複合、纖維交聯（cr〇ss_lmkmg)(步$ 1〇8)。最後，將交聯後的複合纖維製成不織布（步驟u〇)， 此過程以實施例為例詳述如下。 赏施例一止血不織布 參照第2圖，其係繪示本發明一實施例之止血不織布之 製備流程。首先，將5公克海藻酸納、〇 7公克的白复盘 公克勝原蛋白加入140毫升蒸館水中，以配製成紡絲原液 (步驟搬）。同時，將50克的氣⑽加入1〇〇〇毫升體積百 分比為鄕的乙醇溶液中，以配製成—金屬鹽成型液（步驟 2〇十接者，進行濕式纺絲，將上述配製好的紡 纺口擠人金屬鹽成型液巾（㈣2q6)。由於，海驗鋼^ 納離子會與金屬鹽成型液中的_子發生離子交換 知辦離子與海藻酸鍵結形成海藻酸妈，進而與膠原蛋 白芨形成複合纖維。 〜〜"、王里a苁千浪没馬〇 5% 酿（gun㈣ldehyde)巾，以使所形成的複合纖維進行 1322839 反應使複合纖維形成交聯架橋結構（步驟208)。最後，將 交聯聚合後的複合纖維剪成短纖後，以水抄法製成不 (步驟210) 〇1322839 IX. Description of the invention: [Technical field to which the invention pertains] The present invention relates to a method for preparing a non-woven right-handed system, and in particular to a method for preparing a hemostatic non-woven fabric and an application thereof. [Prior Art] Collagen is an animal-like polymer. When the blood vessel wall is damaged, collagen immediately binds to platelet membrane bilirubin, and (4) platelets adhere to the wound to form a thrombus to achieve hemostasis. Features. Although collagen has been gradually applied to hemostatic dressings, it is extremely decomposable due to the excellent biodegradability of the shoulders. This is a combination of sodium acetate and collagen, and the J^ dry technology is made into a porous body or a sponge (sp〇nge) to strengthen its mechanical properties. However, such a porous hemostatic material has a slow liquid absorption rate, and thus is prone to back osmosis, and it is impossible to keep the wound dry and easily cause infection. There are other types of ▲ dressings on the market, but there are also many missing temples. For example, seaweed tablets made of alginate have '4 natural plant polymers, so the biocompatibility with animal cells is: strengthening the hemostatic gauze made of nx oxidized cellulose, No eve promotes blood clotting, and quickly achieves hemostasis in (iv) time. 1322839 Therefore, 'the new hemostatic material is still to be developed', in addition to having good biocompatibility, it can provide a better aspiration rate, and (4) it can promote the coagulation rate to keep the wound dry. SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a hemostatic nonwoven fabric for providing better liquid absorbency and for promoting blood clotting speed. According to the above object of the present invention, a method of preparing a hemostatic nonwoven fabric is proposed. First, a spinning dope and a metal salt forming solution are separately prepared, and the spinning dope contains alkali gold alginate, collagen, and chalk. Next, wet spinning is carried out to form a composite fiber of the above-mentioned spinning dope and metal salt molding liquid. Then, the composite fiber is crosslinked and polymerized by a crosslinking agent, and finally, the crosslinked polymerized fiber is made into a non-woven fabric. Another object of the present invention is to provide a hemostatic nonwoven fabric comprising at least a plurality of composite fibers. In addition to cross-linking, the composite fibers comprise calcium alginate, chalk and collagen, wherein collagen, chalk and calcium alginate are uniformly mixed, wherein the mixed weight ratio of alkaline earth alginate to collagen is 1:9-9:1, and the weight of the white peony is 0.01-1.0% of the sum of the weight of the alginate and collagen of the soil tester. Compared with the traditional hemostatic dressing, the above-mentioned hemostatic non-woven fabric not only has better blood adsorption property, but also can achieve blood coagulation in a short time, which is helpful for wound healing. [Embodiment] In an embodiment of the present invention, a method for preparing a hemostatic non-woven fabric is proposed, and during the preparation process, collagen and a common Chinese medicine, white peony, are added to enhance biocompatibility and promote coagulation. Caught. Referring to Fig. 1, there is shown a schematic flow chart of preparation of a hemostatic nonwoven fabric in an embodiment of the present invention. First, a spinning dope containing alkali gold alginate, white complex and collagen is prepared (step 1G2). Further, a metal salt molding liquid is prepared (step 1G4). Then, wet spinning is carried out to form a composite fiber of the spinning dope and the metal salt forming liquid (Step 1〇6). Next, when the composite fiber is foamed in the crosslinking agent, the ruthenium complex and the fiber crosslink (cr〇ss_lmkmg) (step $1〇8). Finally, the crosslinked composite fiber is made into a non-woven fabric (step u〇), and the process is described in detail below by way of examples. Appreciation Example 1 Hemostasis Nonwovens Referring to Fig. 2, there is shown a preparation process of a hemostatic nonwoven fabric according to an embodiment of the present invention. First, 5 g of sodium alginate and 7 g of white lycopene were added to 140 ml of steaming water to prepare a spinning dope (step transfer). At the same time, 50 grams of gas (10) is added to a volumetric solution of 1% by volume of hydrazine in ethanol to prepare a metal salt forming solution (step 2 〇 ten picker, wet spinning, the above preparation Spinning spinning mouth extruded metal salt molding liquid towel ((4) 2q6). Because, Haizheng steel nano ion will ion exchange with _ sub in metal salt molding liquid, and ion and alginic acid bond to form alginic acid mother, and then Forming a composite fiber with collagen bismuth. ~~", Wang Li a 苁 浪 没 〇 〇 gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun gun Finally, after the crosslinked polymerized composite fiber is cut into staple fibers, it is produced by water copying (step 210).
。於本發明之另一實施例中，紡絲原液中的海藻酸鈉，以 可用其他鹼金族海藻酸鹽代替，其於紡絲原液中的重量百 分率濃度係為（Μ，％。而膠原蛋白之重量百分率濃度係為 〇_Μ〇%’白复之重量百分率濃度則為0.01-1.0%。此外， 用來製備紡絲原液之溶劑亦可為其他親水性溶劑，例如甲 醇或乙醇。再則’金屬鹽成型液中之所使用的金屬鹽可為 鹼土金屬鹽’其重量百分率濃度係為0.01-15%，另外可使 用Τ醇、乙醇或丙酮溶液作為金屬成型液之溶劑，其重量 百为率濃度係為3G-7G%〇當驗金族海㈣鹽與鹼土金屬離 子相接觸時，會發生離子交換，進而形成鹼土 之複合纖維析出。 '、^. In another embodiment of the present invention, the sodium alginate in the spinning dope is replaced by other alkali gold alginate, and the concentration percentage in the spinning dope is (Μ, %. and collagen). The weight percentage concentration is 〇_Μ〇%', and the weight percentage concentration of Baifu is 0.01-1.0%. In addition, the solvent used to prepare the spinning dope may be other hydrophilic solvents such as methanol or ethanol. 'The metal salt used in the metal salt molding liquid may be an alkaline earth metal salt' having a weight percentage concentration of 0.01 to 15%, and a decyl alcohol, ethanol or acetone solution may be used as a solvent for the metal molding liquid, and the weight thereof is When the concentration is 3G-7G%, when the gold (4) salt is in contact with the alkaline earth metal ions, ion exchange occurs, and the composite fiber of the alkaline earth is precipitated. ', ^
於本發明之另—實施例中’作為交聯劑的戊二路亦可使 用綠料素（genipm)代替。而交聯劑的重量百分率濃度係為 1°U°。另外，交聨聚合後的複合纖維則利用針紮法製 :本發月之另Λ施例中’係提供__種止血不織布。此 種止血不織布包含複數個複合纖維。該些複合纖維除了交 聯成型外’其成分包含耗酸㉙、白芨以及膠原蛋白，其 中膠原蛋白、白复與㈣賴係均句混合，其中驗土族海 f酸鹽與膠原蛋白之混合重量比係為1:9-9:1，而白芨之重 量係為鹼土族海藻g㈣與勝原蛋白重量總和之 目容性測詁. · ° 1322839 為了測式所製備出的止血不織布是否具有良好的生物 相容性’因此依據國際標準化组織（in_ati〇nai Organization for Standardizati〇n)所制定之 ISO10993-PART4方法，進行測試。 於此測試方法中，係將測試樣品與兔子血液相混合， 若測試樣品之生物相容性不佳’則會造成溶血現象，使紅 ^球破裂’進而釋放出血紅素。而利用所釋放出血紅素的 量，則可以下式⑴計算出測試樣品的溶血指數。 溶血指數=(毫克/毫升） 早位體積原血紅素的量（毫克/毫升）x100% 最後，再將所測得的溶血指數與IS〇1_3_PART4方法 中，所制定㈣㈣血指標奸_。而 血不織布的測試結果，如表—所示。 貝以止 ^11_^1^!^性測試纟^ ✓谷血程度 溶血指數 益 *♦»、 輕微 測試樣品 二 0-2% M0% 中等 11-20% 21-40% 大於40% 有效陽性對照組之測試值為> 85% 有效陽性對照組之測試值為< 2% 測試組 陽性對照組 9 量基指標，係作為測試結果的評 照組之測試樣品為注射用蒸館：，：=f中陽性對 85.25%，對照左側之標準溶血 1冷血指數為 =加入術後’血球細胞内外梅透愿差，而使 入血球内部。隨著血球細胞内 致細胞膜的破裂，致使血紅素釋出，產生溶血現象¥ 至於陰性對照組之測試樣品為高密度聚 =tyrethyl—^ 此係i於:广則二標準溶血指標’屬於無溶血現象產生。 回拉度聚乳乙稀不會造成血液滲透塵的改變，故 紅血球不會破裂，無溶血現象產生。至於測試組中，則為 广血不織布之萃取液與兔子血液，所測得的溶血 ^駕’對照標準溶企指標可知，止以織布並不會造成溶 血現象’據此，本發明之實施例的止也不織布具有良好的 生物相容性。 (=-)血液吸附測誠 為了測試所製得的止血不織布是否具有較佳的企液吸 附性，因此藉由測定纖維素原（Flbrinogen)濃度，進行血液 吸附測試，並與海藻酸納與膠原蛋白所製成的多孔體止血 材，以及由海藻酸鹽所製成的海藻片進行比較，其測試方 法如下。 T先’取10毫克的樣品放入重量百分率為〇 3%的纖 維素原（Fibrinogen)溶液中，於37qc下放置24小時使纖 10 维原吸附在測試樣品上，再利用二辛可寧酸（bicinch〇nmic =，BCA)法測試所吸附纖維素原的量。：辛可寧酸法是 」用血液中的蛋白質(即纖維素原)會將兩價鋼離子還原成 一價的銅離子，所生成的-價銅離子又可與二辛可寧酸形 成錯合物而呈色’最後藉由吸收度的測試來決定所吸附蛋 白質的量。由於纖維素原係為血Η的—種蛋㈣，據此， 料知測試樣品對於纖維素原的吸附性，即相當於得知測 5式樣品對於血液的吸附性。 第3圖則顯示了血液吸附測試之結果，樣品㈧為以海 邊酸鹽製成的m (購自維康醫療用品n材公，商品名 制），樣品（咖為纽體止血材⑽自維康^用 口口益材公司，商品名為sp_Qstan)，而樣品⑷為實施例一 所製備之止血不織布。由第3圖可知，每毫克的止血不織 :則可吸附0.83毫克的纖維素原 '然而，於同樣的單位重 里下，海藻片僅可吸附〇58毫克的纖維素原，多孔性止血 材吸附性更差’只有〇 25毫克。由此可知，止 其他止血敷料相較的確具有較佳的血液吸附性。4 1_三）凝血沏丨就 為了驗證上述之止血不織布，除了具有良好的血液吸 附性外，亦可促進凝金，因此，使用凝血分析儀進行測試， 並與以氡化纖維素所製成之紗布進行比較。同時，為了驗 證所添加之白芨對於凝血效果有極大助益，因此，亦設置 一對照組以進行比較，其結果如表二所示。 表一滅血測試結In another embodiment of the present invention, the pentane pathway as a crosslinking agent may also be replaced by genipm. The weight percent concentration of the crosslinker is 1 ° U °. In addition, the conjugated fiber after the cross-linking polymerization is produced by the needle-punching method: in the other embodiment of the present month, the __ type of hemostatic non-woven fabric is provided. Such a hemostatic nonwoven fabric comprises a plurality of composite fibers. In addition to cross-linking, the composite fibers contain acid-consuming 29, chalk and collagen, among which collagen, Baifu and (4) Lai are mixed, and the weight ratio of the soil-producing salt to the collagen is determined. The system is 1:9-9:1, and the weight of the white peony is the gravitational measurement of the sum of the weight of the alkaline earth seaweed g(4) and the ginseng protein. · ° 1322839 Whether the hemostatic non-woven fabric prepared for the test has a good biological phase Capacity' is therefore tested in accordance with the ISO 10993-PART4 method developed by the International Organization for Standardization (ISO) (in_ati〇nai Organization for Standardizati〇n). In this test method, the test sample is mixed with the blood of the rabbit. If the test sample has poor biocompatibility, it will cause hemolysis, causing the red ball to rupture and release hemoglobin. Using the amount of hemoglobin released, the hemolysis index of the test sample can be calculated by the following formula (1). Hemolysis index = (mg / ml) The amount of proto-hemoglobin in the early volume (mg / ml) x 100% Finally, the measured hemolysis index and the IS 〇 1_3_PART4 method, the (four) (four) blood index _. The test results of blood non-woven fabrics are shown in the table.贝以止^11_^1^!^ Sex test 纟^ ✓ Gu blood degree hemolytic index benefit *♦», slight test sample 2 0-2% M0% Medium 11-20% 21-40% Greater than 40% Effective positive control The test value of the group is > 85% The test value of the valid positive control group is < 2% The positive control group of the test group 9 The base value index, and the test sample of the evaluation group as the test result is the steaming hall for injection:,: =f positive in the pair of 85.25%, the standard hemolysis 1 cold-blood index on the left side of the control = added to the post-hemoglobin cells inside and outside the plum, and into the blood. With the rupture of the cell membrane in the blood cell, the hemoglobin is released, resulting in hemolysis. ¥ As for the negative control group, the test sample is high-density poly = tyrethyl-^ This is the following: the broad standard hemolytic index 'is no hemolysis The phenomenon occurs. The pullback polylactic acid does not cause a change in blood infiltration dust, so the red blood cells will not rupture and no hemolysis occurs. As for the test group, it is the extract of the blood-free non-woven fabric and the blood of the rabbit, and the measured hemolysis test is based on the comparison of the standard solvent index, and it is known that the weaving does not cause hemolysis. According to this, the implementation of the present invention The non-woven fabrics of the examples have good biocompatibility. (=-) Blood Adsorption Test In order to test whether the prepared hemostatic non-woven fabric has better liquid-liquid adsorption, blood adsorption test is carried out by measuring the concentration of fibrinogen (Flbrinogen), and with sodium alginate and collagen The porous hemostatic material made of the protein and the seaweed sheet made of alginate were compared, and the test method was as follows. T first 'take 10 mg of the sample into a 5% by weight solution of Fibrinogen solution, place at 37qc for 24 hours to adsorb the fiber 10 virgin on the test sample, and then use bicinchoninic acid. The amount of cellulose adsorbed was tested by the (bicinch〇nmic =, BCA) method. The Cinchonine method is that the protein in the blood (ie, cellulose) reduces the divalent steel ions to monovalent copper ions, and the resulting valence copper ions can be combined with dioctocinic acid. The color of the object is finally determined by the absorbance test to determine the amount of protein adsorbed. Since the cellulose is originally a bloody egg (four), it is known that the adsorption property of the test sample to the cellulose original is equivalent to the adsorption of the blood sample to the blood. Figure 3 shows the results of the blood adsorption test. The sample (8) is m made from the seaside acid salt (purchased from Weikang Medical Products n-gong, the product name), and the sample (the coffee is the hemostatic material (10) self-dimensional Kang ^ uses mouth mouth Yicai Company, trade name is sp_Qstan), and sample (4) is the hemostatic non-woven fabric prepared in Example 1. As can be seen from Fig. 3, every milligram of hemostasis can absorb 0.83 mg of cellulose original. However, under the same unit weight, seaweed tablets can only adsorb 58 mg of cellulose original, and the porous hemostatic material adsorbs. Poor sex 'only 〇 25 mg. From this, it can be seen that other hemostatic dressings do have better blood adsorption properties. 4 1_3) Coagulation in order to verify the above-mentioned hemostatic non-woven fabric, in addition to good blood adsorption, can also promote the coagulation, therefore, using a coagulation analyzer for testing, and made with deuterated cellulose The gauze is compared. At the same time, in order to verify that the added white peony is very helpful for the coagulation effect, a control group is also set for comparison, and the results are shown in Table 2. Table 1 blood test
第一次測試 —-------- 第一次測試 第三次測試 平均值 氧化纖維素紗布 對照組 止血不織布 (未添加白复) 實施例一 止血不織布 (添加白芨）First test —------------- First test Third test Average oxidized cellulose gauze Control group Hemostatic non-woven fabric (no white complex added) Example 1 Hemostatic non-woven fabric (adding white peony)
由声 _ 叮7~-~~~J___ ° 於相同的測贿件下，氧化纖維素紗布 的千料血時間為52 3秒，而對照組為於製備過程中未添 及之止血不織布，其平均凝血㈣為39 1秒。至於添 加白芨之止血不織布的平均凝血時間僅需36.0秒，由此可 知，添加白复的止血不織布，對於凝血效果的確有顯著的 助益。 述可知，本發明上述實施例之止血不織布，除了 具有良好的生物相容料，亦能提供料之吸液速度，、預 防回滲，並可有效促進凝血。 雖然本發明已以較佳實施例揭露如上，然其並非 限定本發明，任何熟習此技藝者，在 和範圍内 用以 不脫離本發明之精神 # ,#可作各社更動—本發明之保護 砣圍當視後附之申請專利範圍所界定者為準。 12 丄 【圖式簡單說明】 為讓本發明之上述和其他目的、特徵、優點與實扩 旎更明顯易懂，所附圖式之詳細說明如下： 例 第1圖係繪示本發明—實施例中，止血不織布 流程圖。From the sound _ 叮7~-~~~J___ ° under the same bribes, the oxidized cellulose gauze has a blood count of 52 3 seconds, while the control group is a hemostatic non-woven fabric that was not added during the preparation process. The average coagulation (4) was 39 1 second. As for the addition of white sputum, the average clotting time of the non-woven fabric is only 36.0 seconds. It is therefore known that the addition of the white hemostatic non-woven fabric has a significant effect on the coagulation effect. It can be seen that the hemostatic non-woven fabric of the above embodiment of the present invention, in addition to having a good biocompatible material, can also provide the liquid absorption speed of the material, prevent back osmosis, and can effectively promote blood coagulation. Although the present invention has been disclosed in the above preferred embodiments, it is not intended to limit the invention, and any skilled person in the art can be used in the scope of the invention without departing from the spirit of the invention. The scope defined in the patent application scope is subject to the definition of patent application. 12 丄 [Simple Description of the Drawings] In order to make the above and other objects, features, advantages and advantages of the present invention more obvious, the detailed description of the drawings is as follows: Example 1 shows the invention - implementation In the example, the hemostatic non-woven flow chart.
第2圖係繪示依照本發明一實施例中，止血不 製備流程圖。 B 第3圖係繪示依照本發明一實施例中，止血不織布血 液吸附測試結果之長條圖。 【主要元件符號說明】Figure 2 is a flow chart showing the preparation of hemostasis in accordance with one embodiment of the present invention. B Fig. 3 is a bar graph showing the results of blood adsorption test of hemostatic nonwoven fabric in accordance with an embodiment of the present invention. [Main component symbol description]
的製備 之 102 :步驟 104 :步驟 106 I步驟 10 8 :步驟 11 〇 :步驟 202 :步輝 204 :步驟 206 :步驟 208 :步驟 210 :步驟 13Preparation 102: Step 104: Step 106 I Step 10 8: Step 11 〇: Step 202: Step Hui 204: Step 206: Step 208: Step 210: Step 13