200423976 (1) 玖、發明說明 【發明所屬之技術領域】 本發明係有關防沾黏用膜及其製法。更詳細說係有關 使用性良好，抑制細胞黏著效果極高之防沾黏用膜，及其 製造方法。 【先前技術】 在心臟外科，整形外科，腦神經外科，腹部外科，婦 產科等之臨床領域，各種外科手術後，或外傷，患部之活 體細胞組織沾黏爲重大問題。組織產生沾黏時，例如，引 起痛覺或機能障礙，嚴重時需另行手術剝離上述沾黏。又 由於沾黏，對原病患再手術產生困難的問題。因此，向來 ’爲防止活體組織沾黏’開發在可能產生沾黏之活體組織 覆蓋、保護之防沾黏用膜，實際上，再生氧化纖維素或透 明質酸·羧基甲基纖維素混合膜等，實用化作爲防沾黏用 例如，提案以氧化纖維素之多層薄膜作爲防沾黏用膜 使用（參閱專利文獻1 )。又，提案以透明質酸·羧基甲 基纖維素冷凍處理之膠質組成物作爲防沾黏用膜（參閱專 利文獻2 )。 但是，此等之防沾黏用膜由於吸收水分而產生黏著性 ，手術中黏著於手套等，使用性有缺點。 提案以活體內分解吸收性聚合物所成之不織布，作爲 使用性良好之防沾黏用膜。例如，提案以膠原爲主的膜所 -5- (2) (2)200423976 成之防沾黏用膜（參閱專利文獻3 )。但是，使用如此之 膠原時，由於膠原爲天然材料，完全除去具有抗原性 telopeptide部份有困難及混入普恩蛋白（prion)等產生 危險性。又，爲抑制防沾黏用膜分解性，使用醛類，異氰 酸類之交聯劑，使用此等於活體內分解之生成物有不良影 響，不理想。 一方面，提案以免疫學無問題之乳酸-二醇酸共聚物 ，乳酸-已內酯共聚物取代膠原之活體內分解吸收性聚合 物所成之防沾黏用膜（參閱專利文獻4 )。又，提案由靜 電紡紗法作成之乳酸或乳酸-二醇酸共聚物之不織布所成 之防沾黏用膜（參閱專利文獻5 )。 特別是，至今所提案之防沾黏用膜，由於該膜對細胞 或組織容易黏著、滲透防止沾黏之效果仍不充分，期望對 細胞或組織之黏著抑制效果高的防沾黏用膜。 專利文獻1 曰本特開平10-99422號公報 專利文獻2 曰本特開2003-19194號公報 專利文獻3 曰本特開平3-295561號公報 專利文獻4 曰本特開昭60-14861號公報 專利文獻5 US2002/ 0173213 號公報 【發明內容】 〔發明之揭示〕 本發明之課題爲提供具有高防沾黏效果，且使用性優 之防沾黏用膜。又，本發明之其他課題爲，提供操作簡便 -6- (3) (3)200423976 ’具有高沾黏效果之防沾黏用膜製造方法。 本發明係如下所述。 1.由活體內分解吸收性聚合物之纖維構造物所成之 防沾黏用fe，其特徵爲形成該纖維構造物之纖維平均直徑 爲0 · 0 5〜5 0 # m，且該纖維構造物之纖維表面構造，具有 0 · 0 1〜1 // m直徑凹陷部，該凹陷部佔有纖維表面之1 〇〜 95%。 2 .纖維構造物爲不織布，如第1項之防沾黏用膜。 3 ·該纖維構造物主要由脂肪族聚酯所成，如第1或 2項之防沾黏用膜。 4 ·纖維構造物主要由聚乳酸所成，如第1或2項之 防沾黏用膜。 5 .由纖維形成性聚合物製造纖維構造物，係經纖維 形成性聚合物以揮發性溶劑溶解之溶液階段，與上述溶液 以靜電紡紗法之紡紗階段，及得到於捕集基板上累積纖維 構造物階段，形成該纖維構造物之纖維平均直徑爲0.05〜 5 〇 // m，且該纖維構造物之纖維表面構造，具有〇 . 0 1〜1 // m直徑凹陷部，該凹陷部佔有纖維表面之1 〇〜9 5 %之 防沾黏用膜之製造方法。 6. 揮發溶劑爲由二氯甲烷，氯仿，二氯乙烷，四氯 乙烷，三氯乙烷，二溴甲烷，溴仿，四氫呋喃，1，4 一二 噁烷所成群中至少選擇1種，如第5項之防沾黏用膜之製 造方法 ° 7. 在該靜電紡紗法紡紗階段，形成纖維狀物質之噴 (4) 200423976 口與捕集基板間的相對濕度爲2 0 %以上，如第 之防沾黏用膜之製造方法。 〔用以實施發明之最佳型態〕 以下詳述發明。本發明使用之纖維構造物， 單數或複數之纖維，由織，編或其他之手法所形 元構造物。單纖維之單絲及集合複數單絲之紗所 次元構造物亦含在其中。 具體的纖維構造物之型態，理想可列舉如不 布，管織品，網織品等。更理想的型態爲不織布 本發明使用之織布構造物之織布表面構造， 徑爲0.0 1〜1 # m之凹陷部。凹陷部之直徑在上 外者組織之黏著抑制效果小，不理想。更理想： 0 · 5 # m。該凹陷部佔纖維表面之1 〇〜9 5 %。 本發明使用之纖維構造物之纖維表面構造， 部佔纖維表面1 0〜9 5 %爲理想。凹陷部佔纖維 例在上述範圍以外者，組織之黏著抑制效果小， 理想凹陷部佔纖維表面之比例爲40〜95 %者， 60〜95%，再理想爲60〜80%。 本發明之防沾黏用膜，必須有該纖維構造物 發明之防沾黏用膜僅爲該纖維構造物所形成亦可 構材組合亦可。可組合之構材，可列舉如，爲固 用膜於手術患部之組織黏著性成分，或強化對縫 補強材料等。與組織黏著性成分組合時，例如可 5或6項 係指層合 成之三次 形成之三 織布，織 〇 係具有直 述範圍以 吾 0.0 2〜 以該凹陷 表面之比 不理想。 更理想爲 。即，本 ，與其他 定防沾黏 合耐性之 於該纖維 -8- (5) 200423976 構造物之一面以組織黏著性成分固定，固定該組織黏 分之面與手術之患部貼合而固定防沾黏用膜，另一面 成由其他防止組織沾黏之構造。 形成本發明使用之纖維構造物之纖維平均纖維 0.0 5〜5 0 // m者爲理想。平均纖維徑低於0 · 0 5 // m時 纖維構造物之強度不能保持不理想。又，平均纖維徑 5 0 // m時，缺乏柔軟性不理想。理想的平均纖維徑爲 〜3 0 y m 〇 本發明之纖維構物主要由活體內分解收性聚合物 時，可無遲延修復活體組織面殘存之組織爲理想。活 分解收性聚合物可列舉如，聚乳酸，聚二醇酸，聚二 ，聚內酯，三甲撐碳酸酯，聚丁撐水楊酸酯，或此等 聚物等之合成聚合物或膠原、甲殻素，殼聚糖，藻朊 透明質酸，澱粉，或此等之衍生物等天然聚合物，依 性或品質控制觀點，以合成聚合物爲理想。其中，脂 聚酯依力學物性與於活體內之分解性爲理想，特以聚 爲理想。聚乳酸之重量平均分子量爲1 0萬以上者， 學物性與於活體內之分解性觀點更爲理想。 此等之活體內分解吸收性聚合物可單獨使用，或 種使用亦可。 本發明使用之纖維構造物之製造方法，能得到具 表面構造之纖維等手法者無特別限制，以靜電紡紗法 想。以下詳細說明有關由靜電紡紗法之製造方法。 本發明使用之靜電紡紗法，係將纖維形成性聚合 著成 可形 徑以 ，該 大於 0.07 所成 體內 噁酮 之共 酸， 抗原 肪族 乳酸 依力 複數 上述 爲理 物以 -9- (6) (6)200423976 揮發性溶劑溶解之溶液於電極間所形成之靜電場中濟出， 溶液向電極曳絲，形成之纖維狀物質累積於補集基板，得 到纖維構造物。纖維狀物質不僅爲完全餾去溶液之溶劑成 爲纖維構造物之狀態，且亦顯示仍含溶劑之溶液狀態。 首先，說明靜電紡紗法之裝置。本發明所使用之電極 ，金屬，無機物，或有機物任合物質亦顯示導電性者爲佳 。又，絕緣物上持有顯示導電性之金屬，無機物，或有機 物之薄膜者亦可。本發明相關之靜電場係形成於一對或複 數之電極間，任一電極附加高電壓亦可。例如亦含使用電 壓値相異之2個高壓電極（例如1 5kV與1 OkV )，與地線 之電極合3個電極時，亦含使用超過3個電極者。 其次，詳細說明由靜電紡紗法之本發明製造方法。首 先爲纖維形成性聚合物揮發性溶劑溶解溶液之階段。本發 明製造方法相關之溶液中之纖維形成性聚合物濃度以1〜 5 0重量％爲理想。纖維形成性聚合物之濃度低於1重量 %時，濃度過低難於形成纖維構造物不理想。又，超過 5 0重量％時，由於溶液粘度增大，電極間必要施加更高 電壓不理想。更理想的纖維形成性聚合物之濃度爲 2〜3 0 重量％。 形成本發明溶液之溶劑，可列舉如二氯甲烷，氯仿， 二氯乙院，四氯乙垸，三氯乙院，二溴甲院，溴仿，丙酮 ，甲醇，乙醇，丙醇，異丙醇，甲苯，四氫呋喃，1，1， i，3，3，3 —六氟異丙醇，1，4 —二噁烷，四氯化碳，環 己烷，環己酮，乙醯腈等。其中，可容易形成具有上述表 -10- (7) (7)200423976 面構造之纖維，以二氯甲烷，氯仿，二氯烷，四氯乙烷， 三氯乙烷，二溴甲烷，溴仿，四氫呋喃，1，4 —二噁烷爲 理想，更以二氯甲烷爲理想。 此等揮發性溶劑可單獨使用，亦可複數之揮發性溶劑 組合使用。又，在本發明，不損害本目的範圍下，亦可倂 用其他不揮發性溶劑。 其次說明上述溶液於靜電紡紗法之紡紗階段。將該溶 液置於靜電場中之擠出，可使用任意的方法。例如以圖1 之一例說明如下。由供給噴口溶液2，將溶液置於靜電場 中適當位置，由該噴口將溶液由電場曳絲纖維化。可使用 適宜的裝置進行，例如注射器之筒狀溶液保持槽3之前端 部以適宜之手段，例如將高電壓產生器6，設置於施加電 壓之注射針狀之溶液噴口 1，將溶液導至該前端。於接地 之纖維狀物質補集電極5適當距離設置該噴口 1之前端， 溶液2由該噴口 1之前端擠出時，於此前端與纖維狀物質 補集器電極5之間形成纖維狀物質。 又，本業者以自知之方法可將該溶液之細滴導入靜電 場中。以下使用圖2之一例說明。此時之唯一要件爲，將 細滴置於靜電場中，離纖維狀物質補集電極5，保持於產 生纖維化之距離。例如，具有噴口 1之溶液保持槽3中之 溶液2，直接插入與纖維狀物質補集器電極對抗之電極4 亦可。 將該溶液由噴口供給靜電場時，使用數個噴口可提高 纖維狀物質之生產速度。電極間的距離，依據帶電量，噴 -11 - (8) (8)200423976 口尺寸，紡紗液流量’紡紗液濃度等，1 0 k V程度時，以 5〜20 cm爲適當。又’附加之靜電電位，一般爲3〜100 kV，理想爲5〜50 kV，更理想爲5〜30 kV。所望之電位 可以任意適切之方法作成。 上述說明，以電極兼補集基板時，電極間設置可作爲 補集基板之物質，電極與補集基板分別設置，於該處可補 集纖維構造物。此時，例如於電極間設置環狀物作爲補集 基板時，可連續生產。 於本發明，噴口與補集基板之間之相對濕度理想爲維 持20 %以上時，可簡便的得到上述表面構造之纖維。更 理想爲的相對濕度2 5〜9 5 %以上。 最後說明得到累積於補集基板之纖維構造物階段。在 本發明’該溶液向補集基板曳絲之間，依條件蒸發溶劑形 成纖維狀物質。於通常之室溫在補集補集至基板爲止之間 溶劑完全蒸發，若溶劑蒸發不充分時亦可於減壓條件下曳 絲。又，曳絲之溫度依據溶劑之蒸發舉動或紡紗液之粘度 ，通常爲0〜50°C。 本發明之防沾黏用膜，在不損及其特徵範圍下，可組 合抗腫瘍劑，抗癌劑，消炎劑或活性型維生素D等之維 生素類，甲狀腺刺激激素等之多肽生理活性物質等藥劑， 可促進組織修復。又，該纖維構造物由活體內分解吸收性 聚合物形成時，其纖維中含上述藥劑時，可持有緩放化機 能。 以下，圖1〜2所使用之符號簡單說明如下記述。 -12- 200423976 Ο) 噴口 紡紗液 紡紗液保持槽 電極 維持狀物質補集電極 高電壓產生器 【實施方式】 以下以實施例說明本發明，本發明不限於實施例。又 以下各實施例，比較例之評價項目依以下手法實施。 [纖維表面構造之凹陷部] 所得纖維構造物表面之掃瞄型電子顯微鏡照相（倍率 2 〇 〇 〇倍及8 0 0 0倍）攝影，其照相由η = 2 0測定凹陷部之 直徑平均値算出。 {平均纖維徑} 所得纖維構造物表面之掃瞄型電子顯微鏡照相（倍率 2 0 〇 〇倍及8 0 0 0倍）攝影’其照相由η = 2 0測定纖維徑平 均値算出。 [細胞黏著性評價]200423976 (1) 发明. Description of the invention [Technical field to which the invention belongs] The present invention relates to an anti-sticking film and a method for producing the same. In more detail, it relates to an anti-adhesion film with good usability and extremely high cell adhesion suppression effect, and a method for manufacturing the same. [Prior art] In the clinical fields of cardiac surgery, orthopedics, neurosurgery, abdominal surgery, obstetrics and gynecology, etc., after various surgical operations or trauma, adhesion of living cell tissues in the affected area is a major problem. When the tissue is sticky, for example, it causes pain or dysfunction, and in severe cases, it needs to be removed by surgery. In addition, due to the stickiness, it is difficult to re-operate the original patient. Therefore, to prevent adhesion of living tissues, anti-adhesion films have been developed to cover and protect living tissues that may cause adhesions. In fact, regenerated oxidized cellulose or hyaluronic acid-carboxymethyl cellulose mixed films, etc. For practical use as an anti-adhesion application, for example, it is proposed to use a multilayer film of oxidized cellulose as an anti-adhesion film (see Patent Document 1). In addition, it is proposed to use a hyaluronic acid-carboxymethyl cellulose frozen gel composition as an anti-sticking film (see Patent Document 2). However, these anti-adhesive films have adhesiveness due to absorption of moisture, and adherence to gloves and the like during surgery, which has disadvantages in usability. It is proposed to use a non-woven fabric formed by decomposing an absorbent polymer in vivo as a good anti-sticking film. For example, a collagen-based membrane is proposed. (5) (2) (2) 200423976 A non-sticking film (see Patent Document 3). However, when using such collagen, since collagen is a natural material, it is difficult to completely remove the antigenic telopeptide portion, and it is dangerous to mix it with prion. In addition, in order to suppress the decomposability of the anti-sticking film, the use of cross-linking agents of aldehydes and isocyanates is not preferable because the use of this product is equivalent to decomposition in vivo. On the one hand, an anti-adhesion film composed of a lactic acid-glycolic acid copolymer and a lactic acid-caprolactone copolymer that decomposes and absorbs polymers in vivo in place of collagen is proposed (see Patent Document 4). In addition, an anti-sticking film made of a non-woven fabric of lactic acid or a lactic acid-glycolic acid copolymer produced by an electrospinning method has been proposed (see Patent Document 5). In particular, the anti-adhesion film proposed so far has an insufficient adhesion effect on cells or tissues, and the effect of anti-adhesion on penetration is still insufficient, and an anti-adhesion film having a high adhesion inhibition effect on cells or tissues is desired. Patent Document 1 Japanese Patent Application Publication No. 10-99422 Patent Document 2 Japanese Patent Application Publication No. 2003-19194 Patent Literature 3 Japanese Patent Application Publication No. 3-295561 Japanese Patent Application Publication 4 Japanese Patent Application Publication No. 60-14861 Document 5 US2002 / 0173213 [Summary of the Invention] [Disclosure of the Invention] The object of the present invention is to provide a non-sticking film having a high anti-sticking effect and excellent usability. It is another object of the present invention to provide a method for producing a film for preventing sticking which has a high sticking effect and is easy to operate -6- (3) (3) 200423976. The present invention is as follows. 1. An anti-sticking fe made from a fibrous structure that decomposes an absorbent polymer in vivo, characterized in that the average diameter of the fiber forming the fibrous structure is 0 · 0 5 to 5 0 # m, and the fibrous structure The fiber surface structure of the object has a depression with a diameter of 0 · 0 1 to 1 // m, and the depression occupies 1 to 95% of the fiber surface. 2. The fiber structure is a non-woven fabric, such as the anti-sticking film of item 1. 3. The fiber structure is mainly made of aliphatic polyester, such as the anti-sticking film of item 1 or 2. 4. The fiber structure is mainly made of polylactic acid, such as the anti-sticking film of item 1 or 2. 5. Fabrication of fibrous structures from fiber-forming polymers is a solution phase where the fiber-forming polymer is dissolved with a volatile solvent, and the spinning phase of the solution with the above-mentioned solution by electrospinning, and is accumulated on the collection substrate. In the fiber structure stage, the average diameter of the fibers forming the fiber structure is 0.05 ~ 5 0 // m, and the fiber surface structure of the fiber structure has a depression of 0. 0 1 ~ 1 // m diameter, the depression Manufacturing method of anti-adhesion film occupying 10 to 95% of the fiber surface. 6. The volatile solvents are at least one selected from the group consisting of dichloromethane, chloroform, dichloroethane, tetrachloroethane, trichloroethane, dibromomethane, bromoform, tetrahydrofuran, and 1,4-dioxane. The method for manufacturing the anti-sticking film as described in item 5 ° 7. At the spinning stage of the electrostatic spinning method, a spray of fibrous material is formed (4) 200423976 The relative humidity between the mouth and the capture substrate is 20% The above is the manufacturing method of the anti-sticking film. [Best Mode for Carrying Out the Invention] The invention will be described in detail below. The fibrous structure used in the present invention, singular or plural fibers, is formed by weaving, knitting or other methods. Monofilament monofilaments and yarn collection of multiple monofilament dimensional structures are also included. Specific types of the fiber structure can be ideally exemplified by non-woven fabric, tube fabric, and net fabric. A more desirable form is a non-woven fabric. The surface structure of the woven fabric of the woven structure used in the present invention has a depressed portion having a diameter of 0.0 1 to 1 # m. The diameter of the recessed part is small, and the effect of suppressing the adhesion of the upper and the outer tissues is small, which is not ideal. More ideal: 0 · 5 # m. The recessed portion occupies 10 to 95% of the fiber surface. The fiber surface structure of the fiber structure used in the present invention is preferably 10 to 95% of the fiber surface. The recessed portion occupies the fiber. For example, the effect of suppressing the adhesion of the tissue is small. The ideal recessed portion occupies 40 to 95% of the fiber surface, 60 to 95%, and more preferably 60 to 80%. The anti-adhesion film of the present invention must have the fiber structure. The anti-adhesion film of the present invention is formed only by the fiber structure. The materials that can be combined include, for example, a tissue adhesive component that is a solid film applied to the affected part of the surgery, or a material that strengthens the seam. When combined with the tissue adhesive component, for example, 5 or 6 items can be referred to as three layers of three woven fabrics. Weaving 0 has a direct range ranging from 0.02 to the ratio of the recessed surface. More ideal is. In other words, this fiber is resistant to adhesion and adhesion to other fibers. 8- (5) 200423976 One side of the structure is fixed with a tissue adhesive component, and the surface on which the tissue adhesion is fixed is adhered to the affected part of the surgery to fix the adhesion. Adhesive membrane, the other side is made of other structures to prevent tissue adhesion. An average fiber of 0.0 5 to 5 0 // m forming the fiber structure used in the present invention is ideal. When the average fiber diameter is less than 0 · 0 5 // m, the strength of the fiber structure cannot be kept unsatisfactory. When the average fiber diameter is 50 / m, the lack of flexibility is not satisfactory. The ideal average fiber diameter is ~ 3 0 y m 〇 When the fibrous structure of the present invention mainly decomposes the polymer in vivo, it is ideal to repair the remaining tissue on the surface of the living tissue without delay. Examples of the biodegradable polymer include polylactic acid, polyglycolic acid, polydi, polylactone, trimethylene carbonate, polybutylene salicylate, or synthetic polymers such as these polymers or collagen Natural polymers such as chitin, chitosan, alginate hyaluronic acid, starch, or derivatives thereof, are ideally synthesized polymers from the standpoint of quality or quality control. Among them, the polyester is ideal in terms of mechanical properties and degradability in vivo, and especially poly is preferred. A polylactic acid having a weight average molecular weight of 100,000 or more is more desirable in terms of physical properties and degradability in vivo. These in vivo degradable absorbent polymers can be used alone or in combination. The method for producing a fibrous structure used in the present invention is not particularly limited to those who can obtain fibers having a surface structure, and it is thought of the electrostatic spinning method. The manufacturing method by the electrostatic spinning method is explained in detail below. The electrostatic spinning method used in the present invention is a fiber forming polymer to form a shapeable diameter, the co-acid of the oxone formed in the body greater than 0.07, the antigen aliphatic lactic acid according to the complex number is -9- ( 6) (6) 200423976 The solution dissolved in the volatile solvent is released in the electrostatic field formed between the electrodes. The solution is drawn toward the electrode, and the fibrous substance formed is accumulated on the supplementary substrate to obtain a fibrous structure. The fibrous substance is not only in a state where the solvent of the solution has been completely distilled off into a fibrous structure, but also shows a state of the solution still containing the solvent. First, the apparatus of the electrostatic spinning method will be described. The electrode used in the present invention is preferably one in which metal, inorganic, or organic substance also exhibits conductivity. The insulator may be a thin film of a metal, an inorganic substance, or an organic substance that exhibits conductivity. The electrostatic field related to the present invention is formed between a pair or a plurality of electrodes, and a high voltage may be applied to any one of the electrodes. For example, it also includes the use of two high-voltage electrodes (such as 15kV and 1 OkV) with different voltages. When three electrodes are combined with the ground electrode, it also includes the use of more than three electrodes. Next, the manufacturing method of this invention by the electrospinning method is demonstrated in detail. The first is the stage where the volatile solvent of the fiber-forming polymer dissolves the solution. The fiber-forming polymer concentration in the solution according to the production method of the present invention is preferably 1 to 50% by weight. When the concentration of the fiber-forming polymer is less than 1% by weight, it is not preferable that the concentration is too low to form a fiber structure. Further, when it exceeds 50% by weight, it is not desirable to apply a higher voltage between the electrodes because the solution viscosity increases. A more desirable concentration of the fiber-forming polymer is 2 to 30% by weight. Examples of the solvent for forming the solution of the present invention include dichloromethane, chloroform, dichloroethane, tetrachloroacetam, trichloroethyl, dibromomethyl, bromoform, acetone, methanol, ethanol, propanol, isopropyl Alcohol, toluene, tetrahydrofuran, 1,1, i, 3,3,3-hexafluoroisopropanol, 1,4-dioxane, carbon tetrachloride, cyclohexane, cyclohexanone, acetonitrile and the like. Among them, it is possible to easily form a fiber having the above-mentioned Table-10- (7) (7) 200423976 surface structure, using dichloromethane, chloroform, dichloroethane, tetrachloroethane, trichloroethane, dibromomethane, bromoform, Tetrahydrofuran, 1,4-dioxane is preferred, and dichloromethane is more preferred. These volatile solvents may be used alone or in combination. In addition, in the present invention, other nonvolatile solvents may be used as long as the purpose is not impaired. Next, the spinning phase of the above-mentioned solution in the electrostatic spinning method will be described. Any method can be used for extruding the solution in an electrostatic field. For example, an example shown in FIG. 1 is described below. The nozzle 2 was supplied with the solution, and the solution was placed in an appropriate position in the electrostatic field, and the solution was fibrillated by an electric field from the nozzle. It can be performed using a suitable device, such as the front end of the cylindrical solution holding tank 3 of the syringe, by a suitable means, such as setting the high voltage generator 6 to the injection needle-shaped solution spout 1 of the applied voltage to guide the solution to the front end. A fibrous substance is formed between the front end of the spout 1 and the fibrous substance supplementary collector electrode 5 when the front end of the spout 1 is set at a proper distance from the grounded fibrous substance supplementary collecting electrode 5. In addition, those skilled in the art can introduce droplets of the solution into an electrostatic field by a known method. An example will be described below using FIG. 2. The only requirement at this time is that the droplets are placed in an electrostatic field, and the collector electrode 5 is kept away from the fibrous substance at a distance where fibrosis occurs. For example, the solution 2 in the solution holding tank 3 having the spout 1 may be directly inserted into the electrode 4 opposing the electrode of the fibrous substance collector. When the solution is supplied to the electrostatic field from the nozzle, the use of several nozzles can increase the production speed of the fibrous substance. The distance between the electrodes depends on the amount of charge, and the nozzle size is -11-(8) (8) 200423976, the spinning solution flow rate, the spinning solution concentration, and so on. At about 10 kV, 5 to 20 cm is appropriate. The additional electrostatic potential is generally 3 to 100 kV, preferably 5 to 50 kV, and more preferably 5 to 30 kV. The desired potential can be created by any appropriate method. In the above description, when an electrode is used as the supplementary substrate, a substance that can be used as the supplementary substrate is provided between the electrodes, and the electrode and the supplementary substrate are separately provided, and the fiber structure can be supplemented there. In this case, for example, when a ring is provided between the electrodes as a supplementary substrate, continuous production is possible. In the present invention, when the relative humidity between the nozzle and the supplementary substrate is preferably maintained at 20% or more, the fiber with the above-mentioned surface structure can be easily obtained. More preferably, the relative humidity is 25 to 95%. Finally, the stage of obtaining the fiber structure accumulated in the supplementary substrate will be described. Between the solutions of the present invention, the solvent is drawn to the collecting substrate, and the solvent is evaporated under conditions to form a fibrous substance. At normal room temperature, the solvent completely evaporates from the supplementary collection to the substrate. If the solvent does not evaporate sufficiently, the filament can be drawn under reduced pressure. In addition, the temperature of the drag wire is usually 0 ~ 50 ° C according to the evaporation behavior of the solvent or the viscosity of the spinning solution. The anti-adhesion film of the present invention can be combined with anti-tumor agents, anti-cancer agents, anti-inflammatory agents or vitamins such as active vitamin D, and peptide physiologically active substances such as thyroid stimulating hormone, etc. Agents can promote tissue repair. When the fibrous structure is formed of a biodegradable absorbent polymer, when the fiber contains the above-mentioned agent, it can have a slow-release function. Hereinafter, the symbols used in FIGS. 1 and 2 will be briefly described as follows. -12- 200423976 〇) Nozzle Spinning solution Spinning solution holding tank Electrode Maintaining substance supplementary collecting electrode High voltage generator [Embodiment] The following describes the present invention with examples, but the invention is not limited to the examples. The evaluation items of the following examples and comparative examples were implemented in the following manner. [Depression of fiber surface structure] Scanning electron microscope photography (magnification of 2000 times and 8000 times) of the surface of the obtained fiber structure was photographed, and the average diameter of the depression was measured by η = 20. Figure it out. {Average fiber diameter} Scanning electron microscope photography (magnification of 2000 and 800 times) of the surface of the obtained fiber structure was taken. The photograph was calculated by measuring the average fiber diameter of η = 20. [Evaluation of cell adhesion]
所得之纖維構造物切取直徑2 0 m m之圓型’以7 0 % 乙醇水溶液浸漬滅菌風乾後，設置於細胞培養襯墊（BD -13- (10) (10)200423976 B i 〇 s c i e n c e s )。薄膜不浸漬培養劑於 2 χ 1 0 5 c e 11 s / m 1 / well播種老鼠胎兒線維芽細胞，井板內投入3 ml之培養 劑以5 % C 0 2，3 7 °C之條件於保溫箱（H e r a e u s )進行培 養2天。 培養後取出培養劑，加入1 ml [之2.5 %戊二醛/磷 酸緩衝液（〇 . 2 Μ磷酸二氫鈉1 9 ml，0.2 Μ磷酸氫鈉8 1 ml，離子交換水100 ml ) = 1/ 9 (體積比）]，於4°C放 置2小時。2小時後以磷酸緩衝液洗淨後，以50，70，90 ，9 5，9 9，5 %乙醇之順序進行脫水。 以掃瞄型電子顯微鏡相攝影。（倍率：1，〇〇〇倍）算 出細胞及細胞外基質之附著面積佔纖維構造物面積之比例 ，算出η = 3之測定平均値。 [實施例1] 聚乳酸（日本島津製作所：商品名「Lacty 903 1」， 重量平均分子量168,000) 1重量份以二氯甲烷（日本和 光純藥工業，特級）9重量份於室溫（22 °C )溶解’作成 溶液。使用如圖2所示裝置。該溶液於纖維狀物質補集電 極5擠出5分鐘。噴口 1之內徑爲〇·8 mm，電壓爲12 kV ，由噴口 1至纖維狀物質補集電極5之距離爲1 2 ，相 對濕度爲3 5 %。所得纖維狀物質以掃瞄型電子顯微鏡（ 日本日立製作所s — 2 4 0 0 )測定時’平均纖維徑爲3 β m ，纖維表面凹陷部之平均外徑爲0 · 1 5 ^ m ’凹陷部之面積 佔纖維面積之比例爲6 8 % °纖維狀物質之掃瞄型電子顯 -14- (11) (11)200423976 微鏡照相如圖3，4所示。 該纖維構造物之細胞黏著性評價結果約爲1 〇 %，知 悉細胞黏著受控制。細胞黏著後之掃瞄型電子顯微鏡照相 如圖5所示。 [比較例1] 聚乳酸（日本島津製作所：商品名「Lacty 9 0 3 1」， 重量平均分子量 168，000) 1重量份以二氯甲烷（日本和 光純藥工業，特級）4.5重量份N，N-二甲基甲胺4.5重 量份於室溫（2 2 °C )溶解，作成溶液。使用如圖2所示裝 置。該溶液於纖維狀物質補集電極5擠出5分鐘。噴口 1 之內徑爲0.8 mm，電壓爲12 kV，由噴口 1至纖維狀物質 補集電極5之距離爲1 0 cm，相對濕度爲3 2 %。所得纖維 狀物質以掃瞄型電子顯微鏡（日本日立製作所S - 2400 ) 測定時，平均纖維徑爲0.5 a m，沒有觀察到纖維表面有 凹陷部。纖維狀物質之掃瞄型電子顯微鏡照相如圖6，7 所示。 該纖維構造物之細胞黏著性評價結果約爲7 0 %，細 胞及細胞基質約略多於纖維構造物全部。細胞黏著後之掃 目田型電子顯微鏡照相如圖8所示。 〔產業上之利用領域〕 本發明係提供具有由具特異表面之纖維所成纖維構造 物’具有極高防沾黏效果之防沾黏用膜，及其製造方法。 -15- (12) 200423976 【圖式簡單說明】 圖1爲本發明之製造方法中’紡紗液於靜電場中擠出 之靜電紡紗法所使用裝置之一例。 圖2爲本發明之製造方法中，紡紗液之微細滴導入於 靜電場中之靜電紡紗法所使用裝置之一例。 圖3爲實施例1所得之纖維構成物之表面（2 0 0 0倍The obtained fiber structure was cut into a circular shape with a diameter of 20 mm and was impregnated with a 70% ethanol aqueous solution, sterilized and air-dried, and then set on a cell culture pad (BD -13- (10) (10) 200423976 B i s c i en c e s). The film was not impregnated with the culture medium at 2 χ 1 0 5 ce 11 s / m 1 / well. The mouse fetal lineage bud cells were seeded, and 3 ml of the culture medium was put into the well plate at 5% C 0 2, 37 ° C for incubation. Box (Heraeus) for 2 days. After incubation, remove the culture medium and add 1 ml of [2.5% glutaraldehyde / phosphate buffer solution (0.2 M sodium dihydrogen phosphate 19 ml, 0.2 M sodium hydrogen phosphate 81 ml, ion-exchanged water 100 ml) = 1 / 9 (volume ratio)] and left at 4 ° C for 2 hours. After 2 hours, it was washed with a phosphate buffer solution, and then dehydrated in the order of 50, 70, 90, 9 5, 9 and 5% ethanol. Photograph with scanning electron microscope. (Magnification: 1,000 times) Calculate the ratio of the adhesion area of cells and extracellular matrix to the area of the fibrous structure, and calculate the measured average 値 of η = 3. [Example 1] Polylactic acid (Shimadzu Corporation: trade name "Lacty 903 1", weight average molecular weight 168,000) 1 part by weight of 9 parts by weight of methylene chloride (Japan Wako Pure Chemical Industries, special grade) at room temperature (22 ° C) Dissolve to make a solution. Use the device shown in Figure 2. This solution was extruded on a fibrous substance-collecting electrode 5 for 5 minutes. The inner diameter of the nozzle 1 is 0.8 mm, the voltage is 12 kV, the distance from the nozzle 1 to the fibrous material supplementary collector electrode 5 is 12 and the relative humidity is 35%. The obtained fibrous substance was measured with a scanning electron microscope (Hitachi Seisakusho, Ltd. s 2400), and the average fiber diameter was 3 β m, and the average outer diameter of the recessed portion on the fiber surface was 0 · 1 5 ^ m 'recessed portion. The area-to-fiber area ratio is 68% ° Scanning type electronic display of fibrous substance -14- (11) (11) 200423976 Microscopic photographs are shown in Figures 3 and 4. The cell adhesion evaluation result of this fibrous structure was about 10%, and it was found that cell adhesion was controlled. Scanning electron micrographs after cell adhesion are shown in Figure 5. [Comparative Example 1] Polylactic acid (Shimadzu Corporation: trade name "Lacty 9 0 3 1", weight average molecular weight 168,000) 1 part by weight of dichloromethane (Japan Wako Pure Chemical Industries, special grade) 4.5 parts by weight N, 4.5 parts by weight of N-dimethylmethylamine was dissolved at room temperature (2 2 ° C) to prepare a solution. Use the device shown in Figure 2. This solution was extruded on the fibrous substance complementary collector electrode 5 for 5 minutes. Nozzle 1 has an inner diameter of 0.8 mm and a voltage of 12 kV. The distance from nozzle 1 to the fibrous material supplementary collector electrode 5 is 10 cm and the relative humidity is 32%. When the obtained fibrous substance was measured with a scanning electron microscope (Hitachi S-2400, Japan), the average fiber diameter was 0.5 a m, and no depressions on the fiber surface were observed. Scanning electron microscope photographs of fibrous substances are shown in Figs. The cell adhesion evaluation result of the fiber structure was about 70%, and the number of cells and cell matrix was slightly more than that of the fiber structure. Scanning after cell adhesion is shown in Figure 8. [Application fields in industry] The present invention provides an anti-adhesion film having a fibrous structure made of fibers having a specific surface and having an extremely high anti-adhesion effect, and a method for producing the same. -15- (12) 200423976 [Brief description of the drawing] Fig. 1 is an example of an apparatus used in the electrostatic spinning method in which the spinning solution is extruded in an electrostatic field in the manufacturing method of the present invention. Fig. 2 is an example of an apparatus used in an electrostatic spinning method in which fine droplets of a spinning solution are introduced into an electrostatic field in the manufacturing method of the present invention. Figure 3 is the surface of the fiber structure obtained in Example 1 (2000 times
)° 圖4爲實施例1所得之纖維構成物之表面（20000倍 )° 圖5爲實施例1所得之纖維構成物對細胞黏著性之評 價（1 0 0 0 倍）。 圖6爲比較例1所得之纖維構成物之表面（8 0 0 0倍 )0 圖7爲比較例1所得之纖維構成物之表面（20000倍) ° Figure 4 shows the surface of the fiber structure obtained in Example 1 (20,000 times). Figure 5 shows the evaluation of cell adhesion of the fiber structure obtained in Example 1 (100 times). Figure 6 shows the surface of the fiber structure obtained in Comparative Example 1 (800 times). Figure 7 shows the surface of the fiber structure obtained in Comparative Example 1 (2000 times).
)0 圖8爲比較例1所得之纖維構成物對細胞黏著性之評 價（ 1 000 倍）。 -16-) 0 Figure 8 shows the evaluation of cell adhesion (1,000 times) of the fiber structure obtained in Comparative Example 1. -16-