TWI264306B - Wound dressings and their preparation - Google Patents

Wound dressings and their preparation Download PDF

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Publication number
TWI264306B
TWI264306B TW89115502A TW89115502A TWI264306B TW I264306 B TWI264306 B TW I264306B TW 89115502 A TW89115502 A TW 89115502A TW 89115502 A TW89115502 A TW 89115502A TW I264306 B TWI264306 B TW I264306B
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Taiwan
Prior art keywords
dressing
collagen
derivative
hyaluronic acid
substrate
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TW89115502A
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Chinese (zh)
Inventor
Ling-Huei Huang
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Shin Era Technology Co Ltd
Wun Taix Chemistry Co Ltd
Ling-Huei Huang
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Priority to TW89115502A priority Critical patent/TWI264306B/en
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Publication of TWI264306B publication Critical patent/TWI264306B/en

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Abstract

The subject invention discloses a wound dressing, which comprises collagen or the derivatives thereof, and hyaluronic acid or the derivatives thereof. The subject invention also provides a process for the preparation of said wound dressing.

Description

1264306 A7 B7 五、發明說明(1 ) 發明背景 (請先閱讀背面之注意事項再填寫本頁) 傷口敷料係為一種敷蓋於傷口之材質,可在傷口剛形成 時,迅速保護傷口以免於病原菌之感染及流失過量的體液 及血液。目前市售的傷口敷料,多僅具保護及殺菌之功 效,並無法提供促進傷口癒合之效果。由於其無法促進傷 口癒合’使得癒合之傷口處多半留下明顯的疤痕。 經濟部智慧財產局員工消費合作社印製 促使傷口癒合之方法’已揭示於許多先前技藝中。例 如,美國專利第5,489,3〇4及5,716,411號係揭示一種傷口或燒 燙傷之皮膚再生方法,該方法係先將膠原蛋白-葡萄糖胺 聚醣(glycosaminoglycan)混合後製成的基質覆蓋於傷口表面, 使得該基質經由健康組織之血管及間葉質細胞(mesenchymal cells)滲入’再塗覆一層經培養的動物或人類之表皮細胞 層’以促使皮膚再生。美國專利第4,614,794號係揭示一種 將植物性多醣(如褐藻酸)與生物性可分解之蛋白質(如膠 原a白)形成多孔性之蛋白質/多醣複合物之方法,該複合 物可作為傷口敷料。美國專利第5,698,228號係揭示一種用 於覆蓋傷口之皮膚替代物,其係為烏賊之甲殼質與魚皮膠 原蛋白之層合物。此外,美國專利第5,977,088號揭示一種 含有治療或促進緩解皮膚疾病之藥劑及透明質酸之醫藥組 合物,該醫藥組合物係利用透明質酸促進或引起藥劑之輸 送至患病之皮膚内,其並可累積及延長藥劑停留在該部 位。 上述之先前技藝中使傷口癒合之方法或敷料,並無法使 傷口癒合之時間能更有效地縮短,且用於大面積及較深之 一 4 一 本紙張尺度適用中國國家標準(CNS)A4規格(210 X 297公爱) 1264306 Λ7 、發明說明(2 傷口,無法避条& 〜尤田Γ厄展。本發明提供一種 之傷口敷料。 +具上逑缺點逼簡單說 圖-係本發明之傷口敷料敷用於傷口後的傷 圖 D組織切片 經 濟 部 智 慧 財 產 局 消 費 合 社 印 製 圖二係根據實例丨之方法所製備之傷口敷料。 圖一係只例2 <製備方法之流程圖。 圖四係實例3之製備方法之流程圖。 圖五係根據實例2之方法所製得 圖。 载科成品照相麗H 差 ίο表示聚胺酯膜基材; π表示自黏性之聚胺酯貼布; 12表示富含胺基或羧基之基材; 13表示經環氧化物活化之活化基材; 20表示含透明質酸之膠原蛋白片; 21表示無菌膠原蛋白溶液; 22表示海綿狀膠原蛋白; 23表示膠原蛋白; 30表示容器模型;及 40表示透明質酸。 發明概述 本發明主要係提供一種傷口敷料 衍生物,以及透明質酸或其衍生物__If: 本纸張尺度適用令國國家標準(CNSM4規格(210 X 297^71264306 A7 B7 V. INSTRUCTIONS (1) Background of the invention (please read the note on the back and then fill out this page) Wound dressing is a material applied to the wound to quickly protect the wound from pathogens when the wound is just formed. Infection and loss of excess body fluids and blood. Currently, commercially available wound dressings only have the effect of protection and sterilization, and cannot provide the effect of promoting wound healing. Because it does not promote wound healing, the healing wounds leave a significant scar. The Ministry of Economic Affairs' Intellectual Property Office, Staff Consumer Cooperatives, Printing Method for Promoting Wound Healing has been revealed in many prior art. For example, U.S. Patent Nos. 5,489, 3, 4 and 5,716,411 disclose a method of skin regeneration for wounds or burns by first covering a wound surface with a matrix of collagen-glycosaminoglycan (glycosaminoglycan). The matrix is allowed to infiltrate into a layer of cultured animal or human epidermal cells via blood vessels and mesenchymal cells of healthy tissue to promote skin regeneration. U.S. Patent No. 4,614,794 discloses a method of forming a porous protein/polysaccharide complex with a vegetable polysaccharide such as alginic acid and a biodegradable protein such as collagen a white, which can be used as a wound dressing. U.S. Patent No. 5,698,228 discloses a skin substitute for covering a wound which is a laminate of squid chitin and fish skin collagen. In addition, U.S. Patent No. 5,977,088 discloses a pharmaceutical composition comprising a medicament for treating or promoting skin irritation and hyaluronic acid, which utilizes hyaluronic acid to promote or cause delivery of a medicament into a diseased skin. The drug can be accumulated and extended to stay in the area. The method or dressing for healing wounds in the prior art described above does not shorten the healing time of the wound more effectively, and is used for a large area and a deeper one. The paper size is applicable to the Chinese National Standard (CNS) A4 specification. (210 X 297 public) 1264306 Λ7, invention description (2 wound, can not avoid the strip & ~ You Tian Γ exhibition. The present invention provides a wound dressing. + 上 逑 逼 逼 逼 逼 逼 - - - - - Wound dressing applied to the wound after the wound D. Tissue section Economic Department Intellectual Property Bureau Consumption Co., Ltd. Printed Figure 2 The wound dressing prepared according to the method of the example. Figure 1 is only a case 2 < Flow chart of preparation method Figure 4 is a flow chart of the preparation method of Example 3. Figure 5 is a diagram prepared according to the method of Example 2. The finished product photo Li H is poorly represented by a polyurethane film substrate; π represents a self-adhesive polyurethane patch; 12 represents a substrate rich in amine or carboxyl groups; 13 represents an activated substrate activated by epoxide; 20 represents a collagen sheet containing hyaluronic acid; 21 represents a sterile collagen solution; Collagen; 23 for collagen; 30 for container model; and 40 for hyaluronic acid. SUMMARY OF THE INVENTION The present invention primarily provides a wound dressing derivative, and hyaluronic acid or a derivative thereof __If: This paper scale applies National Standard (CNSM4 Specification (210 X 297^7)

ψ . 先 閱 讀_ 背 面 之 、 注 意 事 項 再 填I裝 頁I 訂 其包括膠原蛋白或 其 1264306 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明(3 ) 本發明另提供一種製備傷口敷料之方法。 發明詳細說明 本發明主要係提供一種傷口敷料,其包括膠原蛋白或其 衍生物,以及透明質酸或其衍生物,可提供使傷口癒合效 果良妤之敷料,其並可廣泛用於一般傷口及較大或較深之 傷口,可明顯縮短傷口癒合之時間,並可使癒合後之新生 組織與周圍組織之外觀接近,可避免留下明顯的疤痕。 本發明之傷口敷料之一組成分為膠原蛋白(Collagen)或其 衍生物,為皮膚之主要組成蛋白質。適用於本發明之膠原 蛋白’包括但不限於:第一型膠原蛋白、第一型或第三型 膠原蛋白之混合物或其他不同型膠原蛋白之混合物。可製 成任何熟習此項技術者所習知之型式使用,例如海綿狀 (sponge / felt)、薄膜狀(film / sheet / membrane)或膠體狀(gel)。 根據本發明實施例,膠原蛋白或其衍生物可以冷凍乾燥 法、自然乾燥法、真空乾燥法等處理得到所欲之型式。 本發明之傷口敷料之另一組成分為透明質酸或其衍生 物。透明質酸(Hyaluronic acid),為具高黏性之多酷類,具重 覆雙酷葡萄糖酸酸(glucuronic acid)及乙酿胺基葡萄菩(N-acetyl - glucosamine)之聚合分子,分子量介於4,000至8 X 106。 本發明之傷口敷料可進一步包括多醣類,包括但不限 於:軟骨膠硫酸(chondroitin sulfate)、褐藻酸(alginate)、甲殼 質(chitin)、甲殼素(chitosan)及該等多醋之衍生物。 本發明之敷料亦可進一步包括其他之藥劑,包括但不限 於:消炎藥劑、生長素(growth factors)、抗生素或抗感染藥 一 6 一 本紙張尺度適用中國國家標準(CNS)A4規格(210 x 297公釐) 11— 11 I— n m -I H «ϋ ]n u'-*4-^ I n n ·1«1 nfl n II 「,.^ 11 n ·ϋ n In m I f->一口 - - (請先閒讀背面之注意事項再填寫本頁) !264306 A7 五、發明說明(4 劑’或其他可促進傷口癒合之因子。 本發明t傷口敷料可進一步去^ ,、、 T J延 7以衣闽塗佈、黏著及化學鍵 甘 < 方式或任何熟習此項技術者所習知之方式塗覆於— 基^表面,、以方便使用,料隔離感染之效。根據本發明 、土伖方式包括但不限於:⑴表面塗佈,可以塗刷、含浸 ,直接滴上的方式將膠原蛋白等物質塗佈於基材表面:⑺ 黏著,可將膠原蛋白等物質與該基材表面以黏著劑黏著在 起,㈠化學鍵結,可將基材或膠原蛋白等物質活化,或 2二者均活化,再將膠原蛋白等物質與基材反應以形成化 學鍵結,或直接以交聯劑與膠原蛋白等物質及基材反應。 適用之义聯劑包括環氧化物(ep〇xide),戊二醛 、槐子平(gernpin)或碳亞胺酸(carbodlmude)等化學物質。 適用於本發明之基材可為任何熟習此項技術者所習知之 基材’例如紗布、具生物體相容性之高分子合成基材、高 透氧之聚胺酯膜或矽膠膜等。該基材可附以黏性物質,以 將本發明敷料固定於皮膚表面,例如將本發明敷料附著於 一 ο.κ.繃上。 本發明之敷料所包括之膠原蛋白或其衍生物、透明質酸 或其衍生物或多醣類,可以任何熟習此項技術者所習知之 方式處理,例如可製成共混物(hybnd)、混合物或共聚物、 或以含浸的方式處理,或經過化學修飾後予以結合。 依據本發明所製成之敷料其具有生物體相容性,易被生 物體分解及吸收,並可促進傷口瘪合,縮短傷口癒合的時 間’可使傷口組織接近其周邊之組織,而不留下明顯的疤 本紙張尺度適用中國國家標準(CNS)A4規袼(21〇 X 297公爱) (請先閱讀背面之注意事項再填寫本頁)ψ . Read _ Back, Note, and then fill I. I book it including collagen or its 1264306 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed A7 B7 V. Invention Description (3) The present invention further provides a preparation for wounds The method of dressing. DETAILED DESCRIPTION OF THE INVENTION The present invention is generally directed to a wound dressing comprising collagen or a derivative thereof, and hyaluronic acid or a derivative thereof, which provides a dressing for a wound healing effect, which is widely applicable to general wounds and Larger or deeper wounds can significantly shorten the time of wound healing and allow the fresh tissue after healing to be close to the surrounding tissue, avoiding the appearance of significant scarring. One of the composition of the wound dressing of the present invention is divided into collagen (Collagen) or a derivative thereof, which is a main constituent protein of the skin. Collagen suitable for use in the present invention includes, but is not limited to, a mixture of Type I collagen, Type I or Type III collagen, or a mixture of other different types of collagen. Any type of use known to those skilled in the art can be made, such as sponge/felt, film/sheet/membrane or gel. According to an embodiment of the present invention, collagen or a derivative thereof can be subjected to a freeze drying method, a natural drying method, a vacuum drying method or the like to obtain a desired form. Another component of the wound dressing of the present invention is classified as hyaluronic acid or a derivative thereof. Hyaluronic acid (Hyaluronic acid) is a highly viscous cool type with a repeating polymer of glucuronic acid and N-acetyl-glucosamine. From 4,000 to 8 X 106. The wound dressing of the present invention may further comprise polysaccharides including, but not limited to, chondroitin sulfate, alginate, chitin, chitosan, and derivatives of such vinegars. . The dressing of the present invention may further comprise other agents including, but not limited to, anti-inflammatory agents, growth factors, antibiotics or anti-infectives. The paper size applies to the Chinese National Standard (CNS) A4 specification (210 x 297 mm) 11-11 I-nm -IH «ϋ ]n u'-*4-^ I nn ·1«1 nfl n II ",.^ 11 n ·ϋ n In m I f-> - (Please read the back of the note first and then fill out this page) !264306 A7 V. Description of the invention (4 doses or other factors that promote wound healing. The t wound dressing of the present invention can further go to ^,, TJ delay 7 It is applied to the surface of the substrate by means of a coating, adhesion and chemical bonding method, or any method known to those skilled in the art, for convenient use, and the effect of isolating the infection. According to the present invention, the soil method Including but not limited to: (1) surface coating, which can be applied by brushing, impregnating or directly dropping onto the surface of the substrate by means of direct dropping: (7) Adhesive, which can adhere collagen and other substances to the surface of the substrate as an adhesive. Adhesive, (a) chemical bonding, can be substrate or collagen The substance is activated, or both are activated, and then a substance such as collagen is reacted with the substrate to form a chemical bond, or the crosslinking agent is directly reacted with a substance such as collagen and a substrate. Suitable combination agents include epoxides. (ep〇xide), a chemical substance such as glutaraldehyde, gernpin or carbodlmude. The substrate suitable for use in the present invention may be any substrate known to those skilled in the art, such as gauze. a biocompatible synthetic polymer substrate, a highly oxygen permeable polyurethane film or a silicone film, etc. The substrate may be adhered with a viscous substance to fix the dressing of the present invention to the skin surface, for example, the dressing of the present invention Attached to a ο. kappa. The collagen or derivative thereof, hyaluronic acid or derivative or polysaccharide thereof included in the dressing of the present invention can be treated in any manner known to those skilled in the art, for example It can be made into a blend (hybnd), a mixture or a copolymer, or treated by impregnation, or chemically modified. The dressing prepared according to the present invention is biocompatible and easily accessible to an organism. Solution and absorption, and can promote wound healing, shorten the time of wound healing' can make the wound tissue close to the tissue around it, without leaving a clear 疤 paper scale applicable to China National Standard (CNS) A4 regulations (21〇 X 297 public) (Please read the notes on the back and fill out this page)

n n Jr 、 n n ΛΜί I n i ϋ I I 經濟部智慧財產局員工消費合作社印製 1264306n n Jr , n n ΛΜί I n i ϋ I I Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing 1264306

五、發明說明( 經濟部智慧財產局員工消費合作社印參 痕。 本發明另提供—種製備 蛋白或其衍生物與透明質酸…〜万法’包括混綱 本發明<-具體實施例,該製備:生物以製成敷料。根招 膠原蛋白或其衍生物 穷口敷料之方法,可先網 明質酸或其衍生物”:乾μ成-膠原蛋白片’刪 該敷料。本發明…膠原蛋白片再度冷滚乾燥製成 跑物冷編::成:具::::’包括先將膠原蛋白或 浸於透明質酸或其衍生物:二蛋:片,再將該膠原蛋白片 料。 /谷'夜後,再度冷凍乾燥製成敷 下列疋實施例係用於對本發 半、η 非用以限制本發明,任何孰例示說明’並 一 7…白此員技術者根據本發明說明 書之教示所達成之修,及應用,皆屬本發明之範疇。β 實施例 實例1 在聚胺酯膜基材10之表面滴上或塗佈濃度3亳克/亳升之 膠原蛋白液冷柬乾燥以形成具膠原蛋白之傷口敷料,隨後 再塗佈或含浸0.1至10毫克/毫升之透明質酸液,再度冷東 乾燥以形成富含透明質酸之膠原蛋白2 〇傷口敷料。包裝後 再以0.4至4.OMrad之γ -放射線殺菌。該成品如圖二所示, 可作為家庭用傷口敷料或外科敷蓋材料。 實例2 本方法之流程如圖三所示。將3毫克/毫升之無菌膠原蛋 白溶液21置於容器模型3〇中’調整其pH值至中性。於3η 本紙張尺度適用中國國家標準(CNS)A4規格(210 x 297公釐) -—III— — } · I I I I I — II . (請先閱讀背面之注意事項再填寫本頁) 1264306 Λ7 B7 五、發明說明(6 ) (請先閱讀背面之注意事項再填寫本頁) 下凝膠0.2至24小時後’取出進行冷;東乾燥’使其成為海绵 狀膠原蛋白22,含浸或滴上〇.1至10毫克/毫升之透明質酸 液後,再度冷凍乾燥,並與具自黏性之聚胺酯貼布11黏合 後,即成為傷口敷料’其成品如圖五所示。 實例3 以雙環氧化物與冨含胺基之基材12於常溫下反應’或與 富含瘦基之基材於90至130°c下反應以製成活化基材13。接 著以去離子水洗滌未反應之雙環氧化物,然後與濃度1至 10毫克/毫升之膠原蛋白23之溶液在常溫下反應4至120小 時後,進行冷;東乾燥,得到共價键結之膠原蛋白基材,此 即為成品A。亦可將成品A含浸或滴上濃度為0.01至20毫克 /毫升之透明質酸40 ’再進行冷凍乾燥,得到產品B。此方 法及產品如圖四所示。 實例4 實例3中之成品A所含浸或滴上之透明質酸,亦可先經化 學修飾或活化,其目的係在於提高透明質酸滯留於傷口的 時間與效果。透明質酸之化學修鋅或活化可以下列三種方 法進行: 經濟部智慧財產局員工消費合作社印製 (方法一):醛基化透明質酸之製備 將透明質酸溶於Na2B4〇7,加入NaBH4反應以進行開環反 應,再進行冷凍乾燥。將經冷凍乾燥之產物溶於間二氮茂 (mudazole),再力口入過碘酸鈉(NaI04)反應,即得到醛基化透 明質酸。 (方法二):胺基化透明質酸之製備 -9 — 本紙張尺度適用中關家標準(CNS)M規格⑵G X 297公釐) --- 1264306 B7 五、發明說明(7 ) 將透明質酸置於1 〇至4〇〇〇毫托耳(丁〇ΓΓ)真空度及常溫1〇至 40 C下’通入叫或ΝΗ3並以20至loot)瓦電力之微波電漿 (plasma),即可將透明質酸改質為胺基化透明質酸。 (方法三):氰溴酸(CNBr)活化之透明質酸之製備 將透明質酸液足pH值調整為14,再加入氰溴酸溶液,並 反應2至60分鐘,即得到氰溴酸活化之透明質酸,未反應 之氰溴酸可以透析法去除。 實例5 如實例丨、2及3製備之敷料方法,其中透明質酸液改用 等量比的透明質酸、褐藻酸、水溶性幾丁聚醣衍生物之混 合液。 實例6 於天竺鼠背部建立2平方公分表面積之全深度傷口, 別放上膠原蛋白敷料,膠原蛋白與透明質酸交聯之敷料 或不含任何物質的Tegaderm敷蓋材,觀察表面傷口疥人時間,並於不同時間點取樣做療合組織的病理切緣, 以判讀傷口癒合時間。 π 根據上述之測試方法測試一般敷科與本發 口徽仝夕fl去,甘Λ丄m 〇 方才十詞於 訂 分 的 傷口癒合之時間,其結果如表 表一 所示: 消 傷口癒合 觀察方法 不含物敷料 膠原蛋白敷料 9〜13天 I_______ - 10 - 本紙張尺度適用中國國家^^)A4規格(2ι〇 χ观公复; 1264306 A7 _B7_ 五、發明說明(8 ) 由表一清楚可知,本發明之傷口敷料較一般敷料確具有 較短之傷口癒合時間。且由圖一可知,本發明之傷口敷料 用於傷口後,癒合組織的結構近於正常的組織結構,遠優 於其他傷口敷料的使用結果,後者具有較緊密的組織結 構。 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製V. Description of the Invention (Inventives of the Intellectual Property Office of the Ministry of Economic Affairs, the Consumer Cooperatives, Printed on the Traces. The present invention further provides a preparation of a protein or a derivative thereof and hyaluronic acid ... ~ Wanfa' including a mixture of the present invention <-specific embodiments, The preparation: the organism is made into a dressing. The method of rooting collagen or its derivative excrement dressing, the first net of acid or its derivative ": dry μ-collagen tablet" delete the dressing. The invention... The collagen tablets are again cold-rolled and dried to make a cold-rolling:::::::'Including collagen or immersion in hyaluronic acid or its derivatives: two eggs: tablets, then the collagen tablets /谷', after the night, re-freeze and dry to make the following 疋 疋 疋 疋 疋 本 本 疋 η η η η η η η η η η η η η η η η η η η η η η η η η η η η η η η η η The repairs and applications of the teachings of the specification are within the scope of the present invention. β Example Example 1 A collagen solution having a concentration of 3 g/μl was applied or dried on the surface of the polyurethane film substrate 10. To form a wound dressing with collagen, Then apply or impregnate 0.1 to 10 mg/ml of hyaluronic acid solution, and then cool it to dry to form hyaluronic acid-rich collagen 2 〇 wound dressing. After packaging, γ-radiation of 0.4 to 4. OMrad Sterilization. The finished product can be used as a home wound dressing or surgical dressing material as shown in Figure 2. Example 2 The flow of the method is shown in Figure 3. The 3 mg/ml sterile collagen solution 21 is placed in the container model 3 〇中' adjust its pH to neutral. For 3η, this paper scale applies Chinese National Standard (CNS) A4 specification (210 x 297 mm) -III-- } · IIIII - II . (Please read the back of the note first) Please fill in this page again) 1264306 Λ7 B7 V. Invention Description (6) (Please read the note on the back and fill in this page). After 0.2 to 24 hours of gel, 'take out for cold; dry east' to make it sponge. Collagen 22, impregnated or dripped with a hyaluronic acid solution of 1 to 10 mg/ml, freeze-dried again, and adhered to the self-adhesive polyurethane patch 11 to become a wound dressing. Shown in 5. Example 3 is double epoxidized Reacting with the ruthenium-containing substrate 12 at normal temperature' or reacting with a substrate rich in lean groups at 90 to 130 ° C to form an activated substrate 13. The unreacted double epoxidation is then washed with deionized water. Then, after reacting with a solution of collagen 23 having a concentration of 1 to 10 mg/ml at room temperature for 4 to 120 hours, it is cooled; and dried in the east to obtain a covalently bonded collagen substrate, which is the finished product A. The finished product A may also be impregnated or dropped with hyaluronic acid 40' at a concentration of 0.01 to 20 mg/ml and then freeze-dried to obtain product B. This method and product are shown in Fig. 4. Example 4 Finished product A in Example 3. The hyaluronic acid contained or dripped may also be chemically modified or activated first, in order to increase the time and effect of hyaluronic acid retention in the wound. The chemical zincing or activation of hyaluronic acid can be carried out in the following three ways: Printing by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumers' Cooperatives (Method 1): Preparation of Aldylated Hyaluronic Acid Dissolving Hyaluronic Acid in Na2B4〇7, Adding NaBH4 The reaction is carried out to carry out a ring opening reaction, followed by freeze drying. The lyophilized product is dissolved in a mudazole and then subjected to sodium periodate (NaI04) to give an aldehyde-based hyaluronic acid. (Method 2): Preparation of Aminated Hyaluronic Acid -9 — This paper scale applies to the Central Standard (CNS) M specification (2) G X 297 mm) --- 1264306 B7 V. Description of invention (7) The acid is placed in a vacuum of 1 〇 to 4 〇〇〇 mTorr (丁〇ΓΓ) and at room temperature 1〇 to 40 C, 'passing into the 叫 or ΝΗ3 and 20 toloot watts of microwave power, The hyaluronic acid can be modified to aminated hyaluronic acid. (Method 3): Preparation of cyanuric acid (CNBr)-activated hyaluronic acid The pH of the hyaluronic acid solution is adjusted to 14, and then the cyanuric acid solution is added, and the reaction is carried out for 2 to 60 minutes to obtain cyanuric acid activation. The hyaluronic acid, unreacted cyanuric acid can be removed by dialysis. Example 5 A dressing method prepared as in Examples 2, 2 and 3, wherein the hyaluronic acid solution was changed to an equal ratio of a mixture of hyaluronic acid, alginic acid, and water-soluble chitosan derivative. Example 6 A full-depth wound of 2 cm 2 surface area was established on the back of the guinea pig. Do not put a collagen dressing, a dressing of collagen and hyaluronic acid cross-linking or a Tegaderm cover material without any substance, and observe the surface wounding time. Samples were taken at different time points for the pathological margin of the healing tissue to determine the time of wound healing. π According to the above test method, the general application and the hairline emblem are taken on the same day, and the time of wound healing is set by the ten words of Ganzi m 〇方才才. The results are shown in Table 1: Method No dressing dressing Collagen dressing 9~13 days I_______ - 10 - This paper size is applicable to Chinese national ^^) A4 specification (2ι〇χ观公复; 1264306 A7 _B7_ V. Invention description (8) It is clear from Table 1 The wound dressing of the present invention has a shorter wound healing time than the general dressing. As can be seen from Fig. 1, after the wound dressing of the invention is applied to the wound, the structure of the healing tissue is close to the normal tissue structure, which is far superior to other wounds. As a result of the use of the dressing, the latter has a tighter organizational structure. (Please read the notes on the back and fill out this page.) Printed by the Consumer Intellectual Property Office of the Ministry of Economic Affairs

1 1X 本紙張尺度適用中國國家標準(CNS)A4規格(210 X 297公釐)1 1X This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm)

Claims (1)

1264306 A BCD ^089115502^ Γ_L文申5月專^奐本(95年5月) 六、申請專利範園 1 · 一種傷口敷料,其包括膠 耸白戍其何生物、透明質酸 升y物’其中透明質酸之濃度為0.01至20毫克/毫 2·如申請專:範圍第Η之敷料,其中透明質酸之濃度為 0 · 1至1 〇耄克/毫升。 3·如申請專利範圍第”員之敷科,其中該敷料得以塗佈、 叉聯或黏著之方式塗覆於-基材表面上。 4·如申請專利範圍第1項之敷料,其中該敷料進一步包括 多醣類。 5.如申請專利範圍第4項之敷料,其中該多酷類係為軟骨 膠硫酸、褐藻酸、甲殼質、甲殼素及該等多醣之衍生 物。 6·如申請專利範圍第1項之敷料,其中該膠原蛋白係為第 一型膠原蛋白、筐一刑七贫 皮曰乐型或乐三型膠原蛋白之混合物或其 他不同型膠原蛋白之混合物。 ” 7. 如申請專利範圍第1項之敷料,其中該膠原蛋白或其衍 生物係呈海綿狀、薄膜狀或膠體狀。 8. 如申請專利範圍第…項之敷科,其中該膠原蛋白或其 衍生物係以冷凍乾燥處理。 9·如申請專利範圍第】項之敷料,其中該膠原蛋白或其衍 生物、夕it類或if明質酸或其衍生物係經化學修飾或活 化° 10·如申請專利範圍第9項之敷料,其中該透明質酸或其衍 生物係經醛基化、胺基酸化或氰溴酸活化。 64997-950530.DOC _____ - 1 _ 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公翁) 1264306 A8 B8 C8 D81264306 A BCD ^089115502^ Γ _L Wenshen May special ^ 奂 ( (May 95) Sixth, apply for patent Fan Park 1 · A wound dressing, which includes the glue white 戍 戍 何 何 透明 透明 透明 透明 透明The concentration of hyaluronic acid is 0.01 to 20 mg/ml. For example, the application of the special: range Η 敷 dressing, wherein the concentration of hyaluronic acid is 0 · 1 to 1 gram / ml. 3. If the application is in the scope of the patent application, the dressing may be applied to the surface of the substrate by coating, cross-linking or adhesion. 4. The dressing of claim 1 of the patent application, wherein the dressing Further comprising a polysaccharide. 5. The dressing of claim 4, wherein the cool type is chondroitin sulfate, alginic acid, chitin, chitin and derivatives of the polysaccharides. The dressing of the first item, wherein the collagen is a mixture of the first type collagen, the basket of the seven-skinned skin type or the type III collagen or a mixture of other different types of collagen. The dressing of the first aspect of the invention, wherein the collagen or a derivative thereof is in the form of a sponge, a film or a gel. 8. The application of the patent scope of the item ... wherein the collagen or its derivative is freeze-dried. 9. The dressing of claim </ RTI> wherein the collagen or derivative thereof, oxime or if-clear acid or a derivative thereof is chemically modified or activated. [10] A dressing wherein the hyaluronic acid or a derivative thereof is activated by aldolization, amino acidification or cyanuric acid. 64997-950530.DOC _____ - 1 _ This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 metric) 1264306 A8 B8 C8 D8 六、申請專利範圍 呀寻利範圍第 ,&gt;,^ 六丁綠胗屌资白或其名 ί =明質酸或其衍生物,係以交聯之方式塗㈣ 12=申請專利範圍第4項之敷科,其中該膠原蛋白或其衣 生物’透明質酸或其衍生物 及多醣類混合物’係以交 聯义万式坌覆於該基材表面。 ”二請專利範圍第&quot;項之敷料,其中交聯之方 化物活化之基材與膠原蛋白進行反應產生 結0 ’其中交聯之方式係為 白進行反應產生共價鍵 如申請專利範圍第12項之敷料 經環氧化物活化之基材與膠原蛋 結。 15、·、如Λ請專利範圍第1,2或3項之敷料,其進一步包括 肖入藥剑、生長素、抗生素或抗感染藥劑,或其他可促 進傷口癒合之因子。 1 種製備傷口敷料之方法,#包括混合膠原蛋白或其 衍生物與透明質酸或其衍生物以製成敷料,其中透明質 酸之濃度為〇.01至20毫克/毫升。 1 7 ·如申叫專利範圍第1 6項之方法,其中透明質酸之濃度 為0.1至10毫克/毫升。 18 ·種製備傷口敷料之方法,其包括先將膠原蛋白或其 折生物冷凍乾燥製成一膠原蛋白片,再將透明質酸或其 衍生物塗佈於該膠原蛋白片再度冷凍乾燥製成該敷料, 其中透明質酸之濃度為0.01至20毫克/毫升。 64997-950530.DOC 本紙張尺度適财關家縣(CNS) Μ規格⑵ό心?公褒) 1264306 申請專利範圍 A8 B8 C8 D8 1 9 ·如申ά青專利範圍n 1 g&gt; …w 万法,其中透明質酸之濃度 為0.1至10¾克/毫升。 2〇· -種製備傷口敷料之方法’纟包括先將膠原蛋白或立 衍生物冷滚乾燥製成-膠原蛋白片,再將該膠原蛋白; : = 衍ί物溶液後,再度冷;東乾燥製成敷 /、透明^鉍之濃度為〇·〇1至20亳克/亳升。 2!.如申請專利範圍第2〇項之敷料,其中透明 為0.1至10毫克/毫升。 阪反 22. 如申請專利範圍第16至21項任何一項之方法,其進一 步包括混合以一多醣類製成敷料。 w 23. 如申請專利範圍第16至21項任何_項之方法,其進一 步包括以塗佈、交聯或黏著之方 八 覆於-基材表面。 切4成(敷料再塗 24. 如申請專利範圍第18至21項任何一項之方法,… 膠原蛋白或其衍生物係製成海綿狀、薄膜狀或膠體狀。以 25. 如申請專利範圍第22項之方法,其中該多醣_ 骨膠硫酸、褐藻酸、甲殼質、曱殼素或該等多醣之衍生 物。 26. 如申請專利範圍第23項之方法,其包括以交聯之方式 將琢製成之敷料再塗覆於一基材表面。 27·如申請專利範圍第26項之方法,其中該交聯之方式係 將基材經環氧化物活化後與膠原蛋白進行反應產生:價 键結。 ^貝 28.如申請專利範圍第16至21項任何—项之方法,其包括 本紙張尺度適用中國國家標準(CNS) Α4規格(210 X 297公釐) 64997-950530.DOC A BCD 1264306 π、申請專利範圍 先將膠原蛋白或其衍生物或透明質酸或其衍生物進行化 學修飾或活化。 29. 如申請專利範圍第28項之方法’其中該透明質酸或其 衍生物進行之化學修飾或活化係為醛基化、胺基酸化或 氰溴酸活化。 30. 如申請專利範圍第16至21項任何一項之方法,其進一 步包括添加消炎藥劍、生甚夺、ρ 朵片J玍長素柷生素或抗感染藥劑, 或其他可促進傷口癒合之因子至敷料中。 64997-950530.DOC 本紙張尺度適用中國國家標準(CNS) A4規格(210 x 297公釐)Sixth, the scope of application for patents, the scope of profit-seeking, &gt;, ^ Six Ding green glutinous white or its name ί = acid or its derivatives, painted by cross-linking (four) 12 = patent application scope 4 The composition of the substrate, wherein the collagen or its coating organism 'hyaluronic acid or a derivative thereof and a mixture of polysaccharides' is coated on the surface of the substrate by cross-linking. "Two patents of the scope of the article", in which the cross-linked square compound activated substrate reacts with collagen to produce a knot 0', wherein the cross-linking method is white to react to produce a covalent bond, such as the scope of patent application The 12-item dressing is epoxide-activated substrate and collagen egg knot. 15. The dressing of Patent No. 1, 2 or 3, which further includes Xiaojianjian, auxin, antibiotic or anti-infection. Medicament, or other factors that promote wound healing. A method of preparing a wound dressing, #include mixing collagen or its derivative with hyaluronic acid or a derivative thereof to prepare a dressing, wherein the concentration of hyaluronic acid is 〇. 01 to 20 mg/ml. 1 7 · The method of claim 16, wherein the concentration of hyaluronic acid is 0.1 to 10 mg/ml. 18. A method for preparing a wound dressing comprising first applying collagen The protein or its degenerate is freeze-dried to form a collagen sheet, and then hyaluronic acid or a derivative thereof is coated on the collagen sheet and then freeze-dried to prepare the dressing, wherein the concentration of hyaluronic acid is 0. .01 to 20 mg/ml. 64997-950530.DOC This paper scale is suitable for Guanjia County (CNS) ΜSpecifications (2) ό心? 公褒) 1264306 Patent application scope A8 B8 C8 D8 1 9 · 如申ά青专利范围n 1 g&gt; ...w method, wherein the concentration of hyaluronic acid is 0.1 to 103⁄4 g/ml. 2〇· - A method for preparing a wound dressing, which comprises first cooling the collagen or the derivative into a cold-dried collagen Protein tablets, then the collagen; : = leaching solution, then cold; East dry made / / transparent ^ 铋 concentration is 〇 · 〇 1 to 20 gram / liter. 2!. The dressing of the second aspect of the invention, wherein the transparent material is 0.1 to 10 mg/ml. The method of any one of claims 16 to 21, further comprising mixing the polysaccharide into a dressing w 23. The method of any of clauses 16 to 21, further comprising coating, crosslinking or adhering the surface of the substrate to the substrate surface. The cut is 40% (the dressing is recoated 24. The method of any one of claims 18 to 21, ... collagen or a derivative thereof The method of claim 22, wherein the polysaccharide _ bone glue sulfuric acid, alginic acid, chitin, chitin or a derivative of the polysaccharide. The method of claim 23, which comprises the step of recoating the dressing made of tantalum to a surface of a substrate by cross-linking. 27. The method of claim 26, wherein the method of crosslinking is The substrate is activated by epoxide and reacted with collagen to produce a valence bond. ^贝28. The method of any of claims 16 to 21, including the paper size applicable to the Chinese National Standard (CNS) Α 4 specification (210 X 297 mm) 64997-950530.DOC A BCD 1264306 π, The scope of the patent application first chemically modifies or activates collagen or its derivatives or hyaluronic acid or its derivatives. 29. The method of claim 28, wherein the chemical modification or activation of the hyaluronic acid or a derivative thereof is aldehyde, amino acid or cyanuric acid. 30. The method of any one of claims 16 to 21, further comprising adding an anti-inflammatory drug sword, a raw material, a sputum tablet, an anti-infective agent, or the like to promote wound healing. The factor is in the dressing. 64997-950530.DOC This paper size applies to the Chinese National Standard (CNS) A4 specification (210 x 297 mm)
TW89115502A 2000-08-02 2000-08-02 Wound dressings and their preparation TWI264306B (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI398276B (en) * 2010-09-20 2013-06-11 Food Industry Res & Dev Inst Method for producing bacterial cellulose with controlled pore size and its use in wound dressing
TWI401098B (en) * 2010-09-09 2013-07-11 Univ China Medical Wound dressing
WO2018192285A1 (en) 2017-04-17 2018-10-25 王宛婷 Composite material
CN115531551A (en) * 2014-07-29 2022-12-30 黄玲惠 Cell tissue gel containing collagen and hyaluronic acid

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI401098B (en) * 2010-09-09 2013-07-11 Univ China Medical Wound dressing
TWI398276B (en) * 2010-09-20 2013-06-11 Food Industry Res & Dev Inst Method for producing bacterial cellulose with controlled pore size and its use in wound dressing
CN115531551A (en) * 2014-07-29 2022-12-30 黄玲惠 Cell tissue gel containing collagen and hyaluronic acid
WO2018192285A1 (en) 2017-04-17 2018-10-25 王宛婷 Composite material

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