TWI845257B - Method for manufacturing water solubility oxide wound dressing - Google Patents

Method for manufacturing water solubility oxide wound dressing Download PDF

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TWI845257B
TWI845257B TW112114290A TW112114290A TWI845257B TW I845257 B TWI845257 B TW I845257B TW 112114290 A TW112114290 A TW 112114290A TW 112114290 A TW112114290 A TW 112114290A TW I845257 B TWI845257 B TW I845257B
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water
oxide
wound dressing
aqueous solution
soluble
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TW112114290A
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Chinese (zh)
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梅乃文
梅惠卿
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梅乃文
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Abstract

The invention provides a method for manufacturing a water solubility oxide wound dressing, comprising: providing distilled water; adding an aqueous solution of oxide salts to the water to form a diluted aqueous solution of oxide salts; passing the diluted aqueous oxide salt solution through an activated carbon adsorption filter to remove trace hydrophobic harmful substances; introducing the diluted oxide salt solution into the magnetization reactor through a flow control valve for a synthesis reaction to form concentrated active oxide water; and adding concentrated active oxide water to water solubility polymers and distilled water to form water solubility oxide wound dressings. Therefore, the dressing obtained by the manufacturing method of the present invention has a function of supplying oxygen, and the dressing can accelerate the healing of various types of wounds and can more effectively protect the active ingredient and achieve the effect of sustained release, thereby increasing the therapeutic activity and reducing epidermal irritation and side effects.

Description

水溶性氧化物傷口敷料之製造方法 Manufacturing method of water-soluble oxide wound dressing

本發明係關於一種水溶性氧化物傷口敷料之製造方法,特別是關於一種可保護活性成分並達到緩釋的效果的水溶性氧化物傷口敷料之製造方法。 The present invention relates to a method for manufacturing a water-soluble oxide wound dressing, and in particular to a method for manufacturing a water-soluble oxide wound dressing that can protect active ingredients and achieve a sustained release effect.

皮膚是人體最大的器官,用於包住脊椎動物的軟層,皮膚擋住外來侵入,亦保住水分,有保暖、阻隔、感覺之用,因此當皮膚上有傷口時,例如一般性創傷或褥瘡所造成的傷口,會使得皮膚受到不利的影響,而無法發揮其正常該有的功能。 The skin is the largest organ in the human body. It is used to cover the soft layer of vertebrates. The skin blocks foreign invasion and retains moisture. It has the functions of warmth, insulation, and sensation. Therefore, when there are wounds on the skin, such as those caused by general trauma or bedsores, the skin will be adversely affected and unable to perform its normal functions.

目前市售傷口敷料的種類繁多,通常針對傷口的性質不同來選擇適當的傷口敷料,並提供傷口良好的癒合環境,阻隔異物並避免環境中的各種細菌、病毒入侵傷口而造成感染。其次,習知對於傷口的處理方式先消毒傷口之後再塗抹藥膏並以紗布進行包覆,等待傷口自行癒合後,再取下紗布等外部包覆固定材料。然而,這種方式對對大面積傷口或因體質問題較難痊癒的傷患(例如糖尿病患者)而言,傷口的復原時間長且要多次換藥,在換藥取下紗布時,常會因紗布等包覆物與傷口的組織液沾黏結合,使傷口受到外力而再次撕裂而導致傷口再次受損,需要更長的癒合時間。 There are many types of wound dressings on the market. Usually, appropriate wound dressings are selected according to the different properties of the wound, and provide a good healing environment for the wound, block foreign matter and prevent various bacteria and viruses in the environment from invading the wound and causing infection. Secondly, the known way to treat the wound is to disinfect the wound first, then apply ointment and cover it with gauze, wait for the wound to heal by itself, and then remove the gauze and other external covering and fixing materials. However, for patients with large wounds or those with physical problems that are difficult to heal (such as diabetics), this method takes a long time to heal and requires multiple dressing changes. When the gauze is removed during the dressing change, the gauze and other covering materials often adhere to the tissue fluid of the wound, causing the wound to be torn again due to external force, resulting in further damage to the wound, requiring a longer healing time.

有鑑於此,本發明人致力於將保溼性敷料與負氧離子結合可形成離子性凝膠,以利於傷口快速癒合。本發明人投入眾多研發能量與精神,不斷於 本領域突破及創新,盼能以新穎的技術手段解決習用之不足,除帶給社會更為良善的產品,亦促進產業發展。 In view of this, the inventor is committed to combining moisture-retaining dressings with negative oxygen ions to form ionic gels, which is conducive to the rapid healing of wounds. The inventor has invested a lot of energy and spirit in research and development, and has continuously made breakthroughs and innovations in this field, hoping to solve the shortcomings of usage with novel technical means, not only to bring better products to the society, but also to promote industrial development.

本發明之主要目的係在提供一種水溶性氧化物傷口敷料之製造方法,透過該製造方法所製得的水溶性氧化物傷口敷料利於壞死組織與纖維蛋白的溶解,並可促進滲液中多種生長因數的釋放,進而達到局部濕潤、減低結痂形成,避免新生肉芽組織機械性損傷,減少更換敷料時損傷和疼痛的目的。其次,本發明的水溶性氧化物傷口敷料可形成封閉性保濕環境,敷料形成屏障使傷口感染機會下降,保護創面神經末梢減少疼痛,同時可達到保持創面恒溫,加快細胞分裂以促進創面癒合,該水溶性氧化物傷口敷料可保護活性成分並達到緩釋的效果。 The main purpose of the present invention is to provide a method for manufacturing a water-soluble oxide wound dressing. The water-soluble oxide wound dressing prepared by the manufacturing method is conducive to the dissolution of necrotic tissue and fibroprotein, and can promote the release of various growth factors in the exudate, thereby achieving the purpose of local moisturizing, reducing scab formation, avoiding mechanical damage to new granulation tissue, and reducing damage and pain when changing dressings. Secondly, the water-soluble oxide wound dressing of the present invention can form a closed moisturizing environment. The dressing forms a barrier to reduce the chance of wound infection, protect the nerve endings on the wound surface and reduce pain. At the same time, it can maintain a constant temperature on the wound surface, accelerate cell division to promote wound healing. The water-soluble oxide wound dressing can protect the active ingredients and achieve a sustained release effect.

為達成本發明上述目的,本發明提供一種水溶性氧化物傷口敷料之製造方法,該方法包含如下步驟,首先,提供一蒸餾水或一礦泉水,並加入一氧化物鹽類水溶液於該蒸餾水或該礦泉水中以形成一稀釋氧化物鹽類水溶液,其中,該氧化物鹽類水溶液係透過一加熱電解法將一高壓氧通入一結晶鹽水溶液而形成,該氧化物鹽類水溶液具有約5.5至8之pH值及5~50mol/L的體積莫爾濃度,且該加熱電解法的加熱溫度控制在40~80℃之間。其次,將該稀釋氧化物鹽類水溶液通過一活性碳吸附濾心以去除微量疏水性有害物質。再者,通過一流量控制閥將該稀釋氧化物鹽類水溶液導入一磁化反應器中以進行一合成反應,該磁化反應器具有一0.1到1特斯拉的磁場及一10到100伏特/厘米的電場,該磁化反應器的一合成溫度控制介於10℃至55℃之間,一合成壓力控制介於6kg/cm2至9kg/cm2之間的高壓,一合成時間為30~90分鐘,以形成一濃縮活性氧化物水。此外,將該濃縮活性氧化物水加熱至65~70℃,加入一水溶性高分子及該蒸餾水或該礦泉水並攪拌3.5~4.5小時,攪拌轉速控制在600~650轉/分,再於真空狀態下攪 拌5~6小時,以形成一水溶性氧化物傷口敷料;其中,該水溶性氧化物傷口敷料包含:45.0~55.0%的該蒸餾水或該礦泉水、15.0~25.0%的氧化物鹽類水溶液及30.0~35.0%的水溶性高分子,以該水溶性氧化物傷口敷料的總重量百分比計。 To achieve the above-mentioned purpose of the present invention, the present invention provides a method for manufacturing a water-soluble oxide wound dressing, the method comprising the following steps: first, providing a distilled water or a mineral water, and adding an oxide salt aqueous solution into the distilled water or the mineral water to form a dilute oxide salt aqueous solution, wherein the oxide salt aqueous solution is formed by passing a high-pressure oxygen into a crystalline salt aqueous solution through a heating electrolysis method, the oxide salt aqueous solution has a pH value of about 5.5 to 8 and a volume molar concentration of 5 to 50 mol/L, and the heating temperature of the heating electrolysis method is controlled between 40 and 80° C. Secondly, the dilute oxide salt aqueous solution is passed through an activated carbon adsorption filter to remove trace hydrophobic harmful substances. Furthermore, the diluted oxide salt aqueous solution is introduced into a magnetizing reactor through a flow control valve to perform a synthesis reaction. The magnetizing reactor has a magnetic field of 0.1 to 1 Tesla and an electric field of 10 to 100 volts/cm. The synthesis temperature of the magnetizing reactor is controlled between 10°C and 55°C, the synthesis pressure is controlled at a high pressure of 6kg/ cm2 to 9kg/ cm2 , and the synthesis time is 30 to 90 minutes to form a concentrated active oxide water. In addition, the concentrated active oxide water is heated to 65-70° C., a water-soluble polymer and the distilled water or the mineral water are added and stirred for 3.5-4.5 hours, the stirring speed is controlled at 600-650 rpm, and then stirred for 5-6 hours under a vacuum state to form a water-soluble oxide wound dressing; wherein the water-soluble oxide wound dressing comprises: 45.0-55.0% of the distilled water or the mineral water, 15.0-25.0% of an aqueous solution of oxide salts and 30.0-35.0% of the water-soluble polymer, based on the total weight percentage of the water-soluble oxide wound dressing.

於本發明之水溶性氧化物傷口敷料之製造方法中,該氧化物鹽類水溶液具有10~40mol/L的體積莫爾濃度。 In the method for manufacturing the water-soluble oxide wound dressing of the present invention, the aqueous solution of the oxide salt has a volumetric molar concentration of 10-40 mol/L.

於本發明之水溶性氧化物傷口敷料之製造方法中,該水溶性高分子係為海藻酸鈉、聚乙烯吡咯烷酮、羧甲基纖維素鈉、透明質酸或其任意組合。 In the method for manufacturing the water-soluble oxide wound dressing of the present invention, the water-soluble polymer is sodium alginate, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, hyaluronic acid or any combination thereof.

於本發明之水溶性氧化物傷口敷料之製造方法中,該水溶性高分子包括:1.0~30.0%的海藻酸鈉、1.0~25.0%的聚乙烯吡咯烷酮及1.0~25.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計。 In the manufacturing method of the water-soluble oxide wound dressing of the present invention, the water-soluble polymer includes: 1.0-30.0% sodium alginate, 1.0-25.0% polyvinyl pyrrolidone and 1.0-25.0% sodium carboxymethyl cellulose, based on the total weight percentage of the water-soluble oxide wound dressing.

於本發明之水溶性氧化物傷口敷料之製造方法中,更包括一加入添加劑步驟,將該稀釋氧化物鹽類水溶液導入至一添加劑槽中,並將臭氧加入至該添加劑槽中以進行殺菌。 The manufacturing method of the water-soluble oxide wound dressing of the present invention further includes an additive adding step, wherein the diluted oxide salt aqueous solution is introduced into an additive tank, and ozone is added into the additive tank for sterilization.

於本發明之水溶性氧化物傷口敷料之製造方法中,該氧化物鹽類水溶液由一金屬元素陽離子與碳酸根、硫酸根、鉻酸根、鎢酸根、鉬酸根、磷酸根、砷酸根或釩酸根相互化合所構成的水溶液。 In the method for manufacturing the water-soluble oxide wound dressing of the present invention, the oxide salt aqueous solution is an aqueous solution composed of a metal element cation and a carbonate, sulfate, chromate, tungstate, molybdate, phosphate, arsenate or vanadate.

於本發明之水溶性氧化物傷口敷料之製造方法中,該金屬元素陽離子包括至少一種二價或三價金屬陽離子,其係為Fe2+、Cu2+、Zn2+、Pb2+、Mn2+、Bi3+或其任意組合。 In the manufacturing method of the water-soluble oxide wound dressing of the present invention, the metal element cation includes at least one divalent or trivalent metal cation, which is Fe 2+ , Cu 2+ , Zn 2+ , Pb 2+ , Mn 2+ , Bi 3+ or any combination thereof.

於本發明之水溶性氧化物傷口敷料之製造方法中,該水溶性氧化物傷口敷料厚度為0.1mm以上且4mm以下。 In the manufacturing method of the water-soluble oxide wound dressing of the present invention, the thickness of the water-soluble oxide wound dressing is greater than 0.1 mm and less than 4 mm.

於本發明之水溶性氧化物傷口敷料之製造方法中,該流量控制閥將該稀釋氧化物鹽類水溶液之流速控制為500~8000L/min。 In the manufacturing method of the water-soluble oxide wound dressing of the present invention, the flow control valve controls the flow rate of the diluted oxide salt aqueous solution to 500~8000L/min.

為達成本發明上述另一目的,本發明提供一種藉由上述水溶性氧化物傷口敷料之製造方法所製得之水溶性氧化物傷口敷料。 In order to achieve the above-mentioned other purpose of the present invention, the present invention provides a water-soluble oxide wound dressing produced by the above-mentioned method for producing a water-soluble oxide wound dressing.

11:容置槽 11: Storage tank

12:活性碳吸附濾心 12: Activated carbon adsorption filter

13:電解磁化裝置 13: Electrolytic magnetization device

14:流量控制閥 14: Flow control valve

15:磁化反應器 15:Magnetic Reactor

151:水溶性高分子 151: Water-soluble polymer

16:添加劑槽 16: Add tank

圖1係為本發明水溶性氧化物傷口敷料之製造方法之流程圖;圖2係為本發明實施例1水溶性氧化物傷口敷料之製備系統;圖3係為本發明實施例2水溶性氧化物傷口敷料之製備系統;圖4A係為糖尿病足在未施用本發明水溶性氧化物傷口敷料時所拍攝之患部照片;圖4B係為糖尿病足在施用本發明水溶性氧化物傷口敷料2天後所拍攝之患部照片;以及圖4C係為糖尿病足在本發明施用水溶性氧化物傷口敷料7天後所拍攝之患部照片。 FIG1 is a flow chart of the manufacturing method of the water-soluble oxide wound dressing of the present invention; FIG2 is a preparation system of the water-soluble oxide wound dressing of Example 1 of the present invention; FIG3 is a preparation system of the water-soluble oxide wound dressing of Example 2 of the present invention; FIG4A is a photograph of the affected part of the diabetic foot taken before the water-soluble oxide wound dressing of the present invention is applied; FIG4B is a photograph of the affected part of the diabetic foot taken 2 days after the water-soluble oxide wound dressing of the present invention is applied; and FIG4C is a photograph of the affected part of the diabetic foot taken 7 days after the water-soluble oxide wound dressing of the present invention is applied.

以下係藉由具體實施例說明本發明之實施方式,熟習此技藝之人士可由本說明書所揭示之內容輕易地瞭解本發明之其他優點與功效。此外,本發明亦可藉由其他不同具體實施例加以施行或應用,在不悖離本發明之精神下進行各種修飾與變更。 The following is a specific embodiment to illustrate the implementation of the present invention. People familiar with this art can easily understand the other advantages and effects of the present invention from the content disclosed in this manual. In addition, the present invention can also be implemented or applied through other different specific embodiments, and various modifications and changes can be made without deviating from the spirit of the present invention.

實施例1 Implementation Example 1

請參照圖1及圖2,圖1係為本發明水溶性氧化物傷口敷料之製造方法之流程圖;及圖2係為本發明實施例1水溶性氧化物傷口敷料之製備系統。 Please refer to Figures 1 and 2. Figure 1 is a flow chart of the manufacturing method of the water-soluble oxide wound dressing of the present invention; and Figure 2 is a preparation system of the water-soluble oxide wound dressing of Example 1 of the present invention.

如圖1及圖2所示,本發明提供一種水溶性氧化物傷口敷料之製造方法,該方法包含:步驟S101:提供一蒸餾水或一礦泉水於一容置槽11中;步驟S102:加入一氧化物鹽類水溶液於該蒸餾水或該礦泉水中以形成一稀釋氧化物 鹽類水溶液;其中,該氧化物鹽類水溶液係透過一加熱電解法將一高壓氧通入一結晶鹽水溶液而形成,該氧化物鹽類水溶液具有約5.5至8之pH值及5~50mol/L的體積莫爾濃度;該氧化物鹽類水溶液較佳地具有10~40mol/L的體積莫爾濃度,該氧化物鹽類水溶液更佳地具有15~35mol/L的體積莫爾濃度,該加熱電解法的加熱溫度控制在40~80℃之間;其中,該氧化物鹽類水溶液由一金屬元素陽離子及碳酸根、硫酸根、鉻酸根、鎢酸根、鉬酸根、磷酸根、砷酸根或釩酸根相互化合所構成的水溶液,該金屬元素陽離子包括至少一種二價或三價金屬陽離子或其任意組合,該金屬元素陽離子較佳為Fe2+、Cu2+、Zn2+、Pb2+、Mn2+或Bi3+。步驟S103:將混有該稀釋氧化物鹽類水溶液通過一活性碳吸附濾心12以去除微量疏水性有害物質。步驟S104:通過一流量控制閥14將該稀釋氧化物鹽類水溶液導入一磁化反應器15中以進行一合成反應,該磁化反應器具有一0.1到1特斯拉之間的磁場及一10到100伏特/厘米之間之電場,因此,當該稀釋氧化物鹽類水溶液通過該磁化反應器15時,水分子中的帶電粒子會受到磁場和電場的作用而發生運動,進而打破水分子中的氫鍵,使氫鍵包覆一氧化物鹽類。此外,該磁化反應器15的一合成溫度控制介於10℃至55℃之間,一合成壓力控制介於6kg/cm2至9kg/cm2之間的高壓,一合成時間為30~90分鐘,以形成一稀釋活性氧化物水。步驟S105:將該稀釋活性氧化物水加熱至65~70℃,加入一水溶性高分子151及該蒸餾水或該礦泉水並攪拌3.5~4.5小時,攪拌轉速控制在600~650轉/分,再於真空狀態下攪拌5~6小時,以形成一水溶性氧化物傷口敷料;其中,以該水溶性氧化物傷口敷料的總重量百分比計包含:45.0~55.0%的該蒸餾水或該礦泉水、15.0~25.0%的氧化物鹽類水溶液及30.0~35.0%的水溶性高分子151,該水溶性高分子151係為海藻酸鈉、聚乙烯吡咯烷酮、羧甲基纖維素鈉、透明質酸或其任意組合;該水溶性高分子151包含:1.0~30.0%的海藻酸鈉、1.0~25.0%的聚乙烯吡咯烷酮及1.0~25.0% 的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計,該水溶性氧化物傷口敷料厚度為0.1mm以上且4mm以下。 As shown in FIG. 1 and FIG. 2 , the present invention provides a method for manufacturing a water-soluble oxide wound dressing, the method comprising: step S101: providing a distilled water or a mineral water in a containing tank 11; step S102: adding an oxide salt aqueous solution into the distilled water or the mineral water to form a dilute oxide salt aqueous solution; wherein the oxide salt aqueous solution is formed by passing a high-pressure oxygen into a crystalline salt aqueous solution by a heated electrolysis method, and the oxide salt aqueous solution has a pH value of about 5.5 to 8 and a volume molar concentration of 5 to 50 mol/L; the oxide The salt aqueous solution preferably has a volume molar concentration of 10-40 mol/L, and the oxide salt aqueous solution more preferably has a volume molar concentration of 15-35 mol/L. The heating temperature of the heating electrolysis method is controlled between 40-80°C; wherein the oxide salt aqueous solution is an aqueous solution composed of a metal element cation and carbonate, sulfate, chromate, tungstate, molybdate, phosphate, arsenate or vanadate, the metal element cation includes at least one divalent or trivalent metal cation or any combination thereof, and the metal element cation is preferably Fe2 + , Cu2 + , Zn2 + , Pb2+ , Mn2 + or Bi3 + . Step S103: The aqueous solution mixed with the diluted oxide salts is passed through an activated carbon adsorption filter 12 to remove trace hydrophobic harmful substances. Step S104: The diluted oxide salts aqueous solution is introduced into a magnetizing reactor 15 through a flow control valve 14 to perform a synthesis reaction. The magnetizing reactor has a magnetic field between 0.1 and 1 Tesla and an electric field between 10 and 100 volts/cm. Therefore, when the diluted oxide salts aqueous solution passes through the magnetizing reactor 15, the charged particles in the water molecules are affected by the magnetic field and the electric field and move, thereby breaking the hydrogen bonds in the water molecules, so that the hydrogen bonds cover the oxide salts. In addition, the synthesis temperature of the magnetizing reactor 15 is controlled between 10°C and 55°C, the synthesis pressure is controlled between 6kg/ cm2 and 9kg/ cm2 , and the synthesis time is 30-90 minutes to form a diluted active oxide water. Step S105: Heat the diluted active oxide water to 65-70°C, add a water-soluble polymer 151 and the distilled water or the mineral water and stir for 3.5-4.5 hours, control the stirring speed at 600-650 rpm, and stir for 5-6 hours under vacuum to form a water-soluble oxide wound dressing; wherein, the water-soluble oxide wound dressing comprises: 45.0-55.0% of the total weight percentage of the active oxide wound dressing; Distilled water or mineral water, 15.0-25.0% aqueous solution of oxide salts and 30.0-35.0% water-soluble polymer 151, wherein the water-soluble polymer 151 is sodium alginate, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, hyaluronic acid or any combination thereof; the water-soluble polymer 151 comprises: 1.0-30.0% sodium alginate, 1.0-25.0% polyvinyl pyrrolidone and 1.0-25.0% sodium carboxymethyl cellulose, and the thickness of the water-soluble oxide wound dressing is greater than 0.1 mm and less than 4 mm, based on the total weight percentage of the water-soluble oxide wound dressing.

本發明的水溶性氧化物傷口敷料採用三維網狀水性凝膠分子技術,該技術特徵在於水凝膠高分子互相連結,形成空間網狀結構,在網狀結構的孔隙中充滿了液體。發生交聯反應的凝膠,由於形成共價交聯網路,凝膠特性表現為溶脹而不溶解。由於水凝膠大量的親水基團,能夠吸收並保持大量水分,因此,本發明的活性氧化物凝膠具有優良的生物相容性、生物可降解性且容易合成,對低分子溶質具有良好的透過性。 The water-soluble oxide wound dressing of the present invention adopts three-dimensional mesh water-based gel molecule technology, which is characterized by the fact that the hydrogel polymers are interconnected to form a spatial mesh structure, and the pores of the mesh structure are filled with liquid. The gel that undergoes cross-linking reaction has the characteristics of swelling but not dissolving due to the formation of a covalent cross-linking network. Due to the large number of hydrophilic groups in the hydrogel, it can absorb and retain a large amount of water. Therefore, the active oxide gel of the present invention has excellent biocompatibility, biodegradability, and is easy to synthesize, and has good permeability to low molecular weight solutes.

傷口癒合測試 Wound healing test

實驗動物1 Experimental animals 1

實驗中所使用是8週大雄性紐西蘭大白兔,體重約為2000~2500g。所有的實驗動物1被飼養於室溫維持在22℃以及相對濕度維持在45%的獨立空調的動物房內,而且水分與飼料被充分地供給。在實驗之前,給予動物至少4週的期間去適應環境。有關實驗動物的飼養環境、處理以及一切實驗程序均符合國家衛生研究院(National Institutes of Health,NIH)的實驗動物飼養管理及使用規範(Guide for the Care and Use of Laboratory Animals)。 The animals used in the experiment were 8-week-old male New Zealand white rabbits weighing about 2000-2500g. All experimental animals1 were kept in an independent air-conditioned animal room with a room temperature maintained at 22°C and a relative humidity maintained at 45%, and water and feed were fully supplied. Before the experiment, the animals were given at least 4 weeks to adapt to the environment. The housing environment, handling and all experimental procedures of the experimental animals were in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals.

皮膚傷口的形成 Formation of skin wounds

將紐西蘭大白兔的背側部分進行剃毛,然後以碘酒以及70%酒精予以消毒後,使用手術刀於紐西蘭大白兔的背部的切出具有一約為2cm×2cm的面積大小以及約為2~3mm的深度的皮膚傷口。 The back of the New Zealand white rabbit was shaved, then disinfected with iodine and 70% alcohol, and a skin wound of approximately 2cm×2cm and 2~3mm deep was cut on the back of the New Zealand white rabbit using a scalpel.

水溶性氧化物傷口敷料成分含量 Content of water-soluble oxide wound dressing ingredients

實驗組1:該水溶性氧化物傷口敷料包含:55%的該蒸餾水或該礦泉水、15.0%的氧化物鹽類水溶液、3.0%的海藻酸鈉、2.0%的聚乙烯吡咯烷酮及25.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計。 Experimental Group 1: The water-soluble oxide wound dressing comprises: 55% of the distilled water or the mineral water, 15.0% of an aqueous solution of oxide salts, 3.0% of sodium alginate, 2.0% of polyvinyl pyrrolidone and 25.0% of sodium carboxymethyl cellulose, based on the total weight percentage of the water-soluble oxide wound dressing.

實驗組2:該水溶性氧化物傷口敷料包含:55.0%的該蒸餾水貨該礦泉水、20.0%的氧化物鹽類水溶液、3.0%的海藻酸鈉、2%的聚乙烯吡咯烷酮及20.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計。 Experimental Group 2: The water-soluble oxide wound dressing comprises: 55.0% of the distilled water or the mineral water, 20.0% of an aqueous solution of oxide salts, 3.0% of sodium alginate, 2% of polyvinyl pyrrolidone and 20.0% of sodium carboxymethyl cellulose, based on the total weight percentage of the water-soluble oxide wound dressing.

對照組1:該水溶性氧化物傷口敷料包含:55%的該蒸餾水或該礦泉水、15.0%的氧化物鹽類水溶液、3.0%的海藻酸鈉、2.0%的聚乙烯吡咯烷酮及25.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計。 Control group 1: The water-soluble oxide wound dressing comprises: 55% of the distilled water or the mineral water, 15.0% of an aqueous solution of oxide salts, 3.0% of sodium alginate, 2.0% of polyvinyl pyrrolidone and 25.0% of sodium carboxymethyl cellulose, based on the total weight percentage of the water-soluble oxide wound dressing.

對照組2:該水溶性氧化物傷口敷料包含:55.0%的該礦泉水或蒸餾水、20.0%的氧化物鹽類水溶液、3.0%的海藻酸鈉、2%的聚乙烯吡咯烷酮及20.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計。 Control group 2: The water-soluble oxide wound dressing comprises: 55.0% of the mineral water or distilled water, 20.0% of an aqueous solution of oxide salts, 3.0% of sodium alginate, 2% of polyvinyl pyrrolidone and 20.0% of sodium carboxymethyl cellulose, based on the total weight percentage of the water-soluble oxide wound dressing.

水溶性氧化物傷口敷料的施用 Application of water-soluble oxide wound dressings

紐西蘭大白兔被隨機地分成2個實驗組以及2個對照組,其中各組的紐西蘭大白兔是依照上述的方法來形成皮膚傷口;接著,實驗組1及2的紐西蘭大白兔的皮膚傷口分別被施用以依據上述實驗組1及2的水溶性氧化物傷口敷料,並在動物的傷口上覆蓋聚氨酯(polyurethane,PU)防水薄膜以保持溼潤。而對照組1及2的紐西蘭大白兔依照上述的方法來形成皮膚傷口;接著,對照組1及2的紐西蘭大白兔的皮膚傷口分別被施用以依據上述對照組1及2的水溶性氧化物傷口敷料。實驗被進行總共歷時14天,在施用敷料之後的第2、6、10及14天之時,分別對各組紐西蘭大白兔的傷口面積進行測量,結果如下表1所示。 New Zealand white rabbits were randomly divided into 2 experimental groups and 2 control groups, wherein the New Zealand white rabbits in each group were formed with skin wounds according to the above method; then, the skin wounds of the New Zealand white rabbits in experimental groups 1 and 2 were respectively applied with the water-soluble oxide wound dressings according to the above experimental groups 1 and 2, and the wounds of the animals were covered with a polyurethane (PU) waterproof film to maintain moisture. The New Zealand white rabbits in control groups 1 and 2 were formed with skin wounds according to the above method; then, the skin wounds of the New Zealand white rabbits in control groups 1 and 2 were respectively applied with the water-soluble oxide wound dressings according to the above control groups 1 and 2. The experiment lasted a total of 14 days. The wound area of each group of New Zealand white rabbits was measured on the 2nd, 6th, 10th and 14th days after the application of the dressing. The results are shown in Table 1 below.

Figure 112114290-A0305-02-0009-1
Figure 112114290-A0305-02-0009-1
Figure 112114290-A0305-02-0010-2
Figure 112114290-A0305-02-0010-2

實驗組1及實驗組2的差異在於氧含量,實驗組2的氧含量高於實驗組1,由上表可知,高氧含量提高了傷口閉合率。其次,實驗組1及實驗組2在動物的傷口上覆蓋聚氨酯防水薄膜以保持傷口溼潤,而對照組1及對照組2並未在動物的傷口上覆蓋聚氨酯防水薄膜,由上表可知,傷口在濕性環境下癒合速度更快。綜上所述,傷口濕性癒合具有以下優勢,首先,有利於壞死組織與纖維蛋白的溶解,濕性環境下,傷口滲出液中的組織蛋白溶解酶,可促進壞死組織的溶解與吸收。其次,調節創面氧張力,促進毛細血管形成,低氧環境刺激毛細血管增生,有利於上皮細胞與膠原生成。再者,促進滲液中多種生長因數的釋放,保留在創面中的滲液釋放並啟動多種酶和酶的活化因數,滲液還能有效地維持細胞的存活,促進多種生長因數的釋放,刺激細胞增殖。此外,保持創面恒溫,加快細胞分裂,促進創面癒合,局部濕潤、減低結痂形成,避免新生肉芽組織機械性損傷,減少更換敷料時損傷和疼痛;保護創面神經末梢,減少疼痛。又,封閉性保濕環境,敷料形成屏障,感染機會下降,密閉狀態下的微酸環境,抑制細菌生長,有利於白細胞繁殖及發揮功能。 The difference between experimental group 1 and experimental group 2 lies in the oxygen content. The oxygen content of experimental group 2 is higher than that of experimental group 1. As can be seen from the table above, high oxygen content improves the wound closure rate. Secondly, experimental group 1 and experimental group 2 cover the wounds of animals with polyurethane waterproof film to keep the wounds moist, while control group 1 and control group 2 do not cover the wounds of animals with polyurethane waterproof film. As can be seen from the table above, the wounds heal faster in a humid environment. In summary, moist wound healing has the following advantages. First, it is conducive to the dissolution of necrotic tissue and fibroblasts. In a humid environment, the tissue protein dissolving enzymes in the wound exudate can promote the dissolution and absorption of necrotic tissue. Secondly, it regulates the oxygen tension of the wound surface and promotes the formation of capillaries. The hypoxic environment stimulates the proliferation of capillaries, which is beneficial to the formation of epithelial cells and collagen. Furthermore, it promotes the release of various growth factors in the exudate. The exudate retained in the wound surface releases and activates various enzymes and enzyme activation factors. The exudate can also effectively maintain the survival of cells, promote the release of various growth factors, and stimulate cell proliferation. In addition, it maintains a constant temperature on the wound surface, accelerates cell division, promotes wound healing, moisturizes the wound locally, reduces scab formation, avoids mechanical damage to new granulation tissue, reduces damage and pain when changing dressings, protects the nerve endings on the wound surface, and reduces pain. In addition, the closed moisturizing environment and the dressing form a barrier, which reduces the chance of infection. The slightly acidic environment in a closed state inhibits bacterial growth and is beneficial to the reproduction and function of white blood cells.

實驗動物2 Experimental Animals 2

實驗動物2係購自國家實驗動物中心之C57BL/6J Narl品系小鼠,體重40~45g,年齡為8週。所有的實驗動物2被飼養於室溫維持在18~26℃以及相對濕度維持在30~70%,光照週期為12小時光照,12小時黑夜的獨立空調的動物房內,而且水分與飼料被充分地供給。有關實驗動物的飼養環境、處理以及一切實驗程序均符合國家衛生研究院的實驗動物飼養管理及使用規範。 Experimental animals 2 were C57BL/6J Narl mice purchased from the National Laboratory Animal Center, weighing 40-45g and aged 8 weeks. All experimental animals 2 were kept in an independent air-conditioned animal room with a room temperature of 18-26℃ and a relative humidity of 30-70%, a light cycle of 12 hours of light and 12 hours of darkness, and sufficient water and feed. The breeding environment, handling and all experimental procedures of the experimental animals were in compliance with the National Institutes of Health's experimental animal breeding management and use regulations.

非感染的傷口處理 Non-infected wound care

手術前將小鼠以腹腔注射方式給予0.6/kg的麻醉劑,待小鼠麻醉後,將其背部毛髮剃除,並在小鼠背部的切出具有一約為1.2cm×1.2cm的面積大 小的皮膚傷口。其次,將小鼠分為空白對照組、凡士林組及實驗組,空白對照組對傷口不進行處理;凡士林組使用棉花棒沾取適量的凡士林後,將其均勻塗抹在傷口上;實驗組使用棉花棒沾取適量的水溶性氧化物傷口敷料後,將其均勻塗抹在傷口上。 Before the operation, the mice were given 0.6/kg of anesthetic by intraperitoneal injection. After the mice were anesthetized, the hair on their backs was shaved, and a skin wound of about 1.2cm×1.2cm was cut on the backs of the mice. Secondly, the mice were divided into a blank control group, a vaseline group, and an experimental group. The blank control group did not treat the wound; the vaseline group used a cotton swab to dip an appropriate amount of vaseline and evenly applied it to the wound; the experimental group used a cotton swab to dip an appropriate amount of water-soluble oxide wound dressing and evenly applied it to the wound.

感染的傷口處理 Infected wound treatment

手術前將小鼠以腹腔注射方式給予0.6/kg的麻醉劑,待小鼠麻醉後,將其背部毛髮剃除,並在小鼠背部的切出具有一約為1.2cm×1.2cm的面積大小的皮膚傷口。再將金黃色葡萄球菌稀釋至105CFU/150μl,並於每隻小鼠加入150μl菌液,使菌液完全滲入皮膚內約5分鐘。其次,將小鼠分為空白對照組、凡士林組及實驗組,空白對照組對傷口不進行處理;凡士林組使用棉花棒沾取適量的凡士林後,將其均勻塗抹在傷口上;實驗組使用棉花棒沾取適量的水溶性氧化物傷口敷料後,將其均勻塗抹在傷口上。 Before surgery, mice were given 0.6/kg of anesthetic by intraperitoneal injection. After the mice were anesthetized, their back hair was shaved and a skin wound of about 1.2cm×1.2cm was cut on the back of the mice. Staphylococcus aureus was diluted to 10 5 CFU/150μl, and 150μl of bacterial solution was added to each mouse, allowing the bacterial solution to completely penetrate the skin for about 5 minutes. Secondly, the mice were divided into a blank control group, a vaseline group, and an experimental group. The blank control group did not treat the wound; the vaseline group used a cotton swab to dip an appropriate amount of vaseline and evenly applied it to the wound; the experimental group used a cotton swab to dip an appropriate amount of water-soluble oxide wound dressing and evenly applied it to the wound.

傷口組織細菌含量試驗 Wound tissue bacterial content test

小鼠實驗第七天後,收集創傷小鼠背部傷口的化膿組織。將組織剪成碎片,並以超音波細胞粉碎機將組織打碎。於4℃下以1,500rpm離心8分鐘後,收集上清液。將該上清液進行序列稀釋,菌液均勻塗抹於瓊脂上後,於37℃培養箱中培養約16小時後,計算菌落數。每克組織所含菌數(CFU/g)=(菌落數*稀釋倍數*10/組織克數)。 On the seventh day of the mouse experiment, the purulent tissue of the back wound of the injured mouse was collected. The tissue was cut into pieces and crushed with an ultrasonic cell crusher. After centrifugation at 1,500rpm for 8 minutes at 4°C, the supernatant was collected. The supernatant was serially diluted, and the bacterial solution was evenly applied to the agar. After incubation in a 37°C incubator for about 16 hours, the number of colonies was calculated. The number of bacteria per gram of tissue (CFU/g) = (number of colonies * dilution multiple * 10/gram of tissue).

結果 result

在非感染的小鼠傷口外觀變化進行評估,在小鼠背部皮膚開創傷口後,每二天清理傷口並更換藥物。相較於其他組別,非感染性傷口以水溶性氧化物傷口敷料進行處理後,其傷口具有較佳的癒合效率。於第8至10天時,空白對照組及凡士林組其傷口癒合並不明顯。相較之下,水溶性氧化物傷口敷料其傷 口外觀已明顯開始癒合。由表2結果顯示,在給予水溶性氧化物傷口敷料治療後,非感染性傷口可約8至10天癒合。 The changes in the appearance of wounds in non-infected mice were evaluated. After the wounds were made on the back skin of the mice, the wounds were cleaned and the medicines were changed every two days. Compared with other groups, the wounds of non-infected wounds treated with water-soluble oxide wound dressings had better healing efficiency. On the 8th to 10th day, the wounds of the blank control group and the vaseline group did not heal significantly. In contrast, the appearance of the wounds of the water-soluble oxide wound dressings had obviously begun to heal. The results in Table 2 show that after treatment with water-soluble oxide wound dressings, non-infected wounds can heal in about 8 to 10 days.

Figure 112114290-A0305-02-0012-3
Figure 112114290-A0305-02-0012-3

而在感染的小鼠傷口外觀變化進行評估,以金黃色葡萄球菌感染傷口,於感染第七天後,每兩天清理傷口並更換藥物。相較於其他組別,感染性傷口以水溶性氧化物傷口敷料進行處理後,其傷口有顯著縮小的趨勢。在第6天時,以水溶性氧化物傷口敷料處理之傷口,已達到60%以上的傷口癒合。於第6天時,空白對照組及凡士林組其傷口尚未開始癒合。相較之下,水溶性氧化物傷口敷料其傷口外觀已顯著開始癒合。由表3結果顯示,於感染的小鼠傷口中給予水溶性氧化物傷口敷料治療後,傷口可提前約8至12天癒合。 The changes in the appearance of the wounds of infected mice were evaluated. The wounds were infected with Staphylococcus aureus. After the seventh day of infection, the wounds were cleaned and the medication was changed every two days. Compared with other groups, the infected wounds treated with water-soluble oxide wound dressings showed a significant shrinkage trend. On the sixth day, the wounds treated with water-soluble oxide wound dressings had achieved more than 60% wound healing. On the sixth day, the wounds of the blank control group and the vaseline group had not yet begun to heal. In contrast, the appearance of the wounds of the water-soluble oxide wound dressings had begun to heal significantly. The results in Table 3 show that after the wounds of infected mice were treated with water-soluble oxide wound dressings, the wounds could heal about 8 to 12 days earlier.

Figure 112114290-A0305-02-0012-4
Figure 112114290-A0305-02-0012-4

抗菌試驗 Antibacterial test

此外,抑制傷口細菌生長以及保護傷口免受感染為照護要點,以ASTM E2315方法進行金黃色葡萄球菌及凝聚桿菌屬(Aggregatibacter)之抗菌試驗,其步驟如下。 In addition, inhibiting the growth of wound bacteria and protecting the wound from infection are the key points of care. The antibacterial test of Staphylococcus aureus and Aggregatibacter was carried out using the ASTM E2315 method. The steps are as follows.

步驟1:取金黃色葡萄球菌經適當時間放大培養後,製備20毫升之菌液,將菌液濃度調整為5x105CFU/mL。 Step 1: Prepare 20 ml of bacterial culture solution by culturing Staphylococcus aureus for an appropriate period of time and adjust the concentration of the bacterial culture solution to 5x10 5 CFU/mL.

步驟2:將步驟1之菌液分為五個組別,五個組別分別作用0小時、0.5小時、1.0小時、2.0小時及4.0小時,每一個組別包括3個樣品,3個樣品包括空白組、實驗組1及實驗組2,空白組為未加入水溶性氧化物傷口敷料;實驗組1為加入水溶性氧化物傷口敷料包括:55%的該蒸餾水或該礦泉水、15.0%的氧化物鹽類水溶液、3.0%的海藻酸鈉、2.0%的聚乙烯吡咯烷酮及25.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計;實驗組2:加入水溶性氧化物傷口敷料包含:55.0%的該礦泉水或該蒸餾水、20.0%的氧化物鹽類水溶液、3.0%的海藻酸鈉、2%的聚乙烯吡咯烷酮及20.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計。 Step 2: Divide the bacterial solution of step 1 into five groups, the five groups are treated for 0 hours, 0.5 hours, 1.0 hours, 2.0 hours and 4.0 hours respectively, each group includes 3 samples, the 3 samples include blank group, experimental group 1 and experimental group 2, the blank group is not added with water-soluble oxide wound dressing; experimental group 1 is added with water-soluble oxide wound dressing including: 55% of the distilled water or mineral water, 15.0% of oxide salt aqueous solution, 3.0% of sea salt Sodium alginate, 2.0% polyvinyl pyrrolidone and 25.0% sodium carboxymethyl cellulose, calculated as a percentage of the total weight of the water-soluble oxide wound dressing; Experimental Group 2: The water-soluble oxide wound dressing was added to include: 55.0% of the mineral water or the distilled water, 20.0% of the oxide salt aqueous solution, 3.0% sodium alginate, 2% polyvinyl pyrrolidone and 20.0% sodium carboxymethyl cellulose, calculated as a percentage of the total weight of the water-soluble oxide wound dressing.

步驟3:分別自各樣品中取0.1毫升之菌液均勻塗抹於培養基上,每一樣品製備兩重覆之培養基,接著於37℃下培養24小時。 Step 3: Take 0.1 ml of bacterial solution from each sample and evenly apply it on the culture medium. Prepare two replicates of culture medium for each sample, and then culture at 37℃ for 24 hours.

步驟4:計數細菌量,並分別以下式計算抑菌率。抑菌率=原接菌量(Log10)-樣品做用後之菌量(Log10)/原接菌量(Log10)x 100%。 Step 4: Count the number of bacteria and calculate the antibacterial rate using the following formula. Antibacterial rate = original inoculum (Log10) - number of bacteria after sample treatment (Log10) / original inoculum (Log10) x 100%.

如上所述,實驗組1及實驗組2的差異在於氧含量,實驗組2的氧含量高於實驗組1,由表4可知,高氧含量提高抗菌率。對金黃色葡萄球菌的抗菌力,其抑制率可達到99.9%。其次,凝聚桿菌屬(Aggregatibacter)之抗菌試驗的方式與金黃色葡萄球菌相同,其抑制率亦可達到99.9%。 As mentioned above, the difference between experimental group 1 and experimental group 2 lies in the oxygen content. The oxygen content of experimental group 2 is higher than that of experimental group 1. As shown in Table 4, high oxygen content increases the antibacterial rate. The antibacterial effect on Staphylococcus aureus can reach an inhibition rate of 99.9%. Secondly, the antibacterial test method of Aggregatibacter is the same as that of Staphylococcus aureus, and its inhibition rate can also reach 99.9%.

Figure 112114290-A0305-02-0013-5
Figure 112114290-A0305-02-0013-5
Figure 112114290-A0305-02-0014-6
Figure 112114290-A0305-02-0014-6

血液中血氧分壓 Blood oxygen partial pressure

無論是靜脈血氧還是動脈血氧在同一個體上,血液中pH、pCO2、pO2之數值接相近,在施用水溶性氧化物傷口敷料後,會增加血液中O2含量以及降低血液中CO2含量,可以提高生物體中的含氧量,以促進傷口癒合速度。 Whether it is venous blood oxygen or arterial blood oxygen in the same individual, the values of pH, pCO2 , and pO2 in the blood are similar. After applying water-soluble oxide wound dressings, the O2 content in the blood will increase and the CO2 content in the blood will decrease, which can increase the oxygen content in the organism and promote the healing speed of the wound.

以本發明的水溶性氧化物傷口敷料之製造方法所製成的該水溶性氧化物傷口敷料具有羧甲基纖維素鈉、聚乙烯吡咯烷酮與海藻酸鈉的特性可形成高黏度的膠體,組成一種含有大量水分的網狀高分子膠體、具黏著性與良好的吸水性;膠體與體表面接觸時可發生反覆水合作用,具有向表面提供水分與吸收滲液的雙重功能,藉以控制出血或體液流失。羧甲基纖維素鈉親水基團吸收水分後變成凝膠狀附著在血管創面,膨脹後形成凝膠層,達成傷口止血。其次,該水溶性氧化物傷口敷料在傷口表面形成保護層,無色透明,高含水性;藉以維持傷口濕潤,避免摩擦、刺激傷口,不傷害新生肉芽組織,減少二次損傷。由於羧甲基纖維素鈉具有酸性的羧基與血紅蛋白中的Fe2+結合,形成棕色黏性膠塊,以達到封閉毛細血管末端而止血。此外,凝膠體對血小板亦有黏附及聚集作用,可以加速凝血。 The water-soluble oxide wound dressing produced by the manufacturing method of the water-soluble oxide wound dressing of the present invention has the characteristics of sodium carboxymethyl cellulose, polyvinyl pyrrolidone and sodium alginate, which can form a high-viscosity colloid, forming a network polymer colloid containing a large amount of water, with adhesion and good water absorption; the colloid can be repeatedly hydrated when in contact with the body surface, and has the dual functions of providing water to the surface and absorbing exudate, thereby controlling bleeding or loss of body fluids. After absorbing water, the hydrophilic group of sodium carboxymethyl cellulose becomes a gel and adheres to the blood vessel wound surface, and after swelling, a gel layer is formed to stop bleeding of the wound. Secondly, the water-soluble oxide wound dressing forms a protective layer on the wound surface. It is colorless, transparent, and highly water-containing. It maintains the moisture of the wound, avoids friction and irritation of the wound, does not damage the new granulation tissue, and reduces secondary damage. Because sodium carboxymethyl cellulose has an acidic carboxyl group, it combines with Fe 2+ in hemoglobin to form a brown viscous gel to seal the end of the capillaries and stop bleeding. In addition, the gel also has an adhesion and aggregation effect on platelets, which can accelerate blood coagulation.

實施例2 Example 2

請參照圖3,圖3係為本發明實施例2水溶性氧化物傷口敷料之製備系統。 Please refer to Figure 3, which is a preparation system for water-soluble oxide wound dressings in Example 2 of the present invention.

如圖3所示,實施例2與實施例1的步驟大致相同,不同處在於:在實施例2中,將該該稀釋氧化物鹽類溶液通過該活性碳吸附濾心12的步驟前,更包括添加臭氧之步驟,將該稀釋氧化物鹽類溶液導入至一添加劑槽16中,並將該臭氧加入至該添加劑槽16中,該臭氧可對該稀釋氧化物鹽類溶液進行殺菌步驟。 As shown in FIG3 , the steps of Example 2 are substantially the same as those of Example 1, except that: in Example 2, before the step of passing the diluted oxide salt solution through the activated carbon adsorption filter 12, an ozone adding step is further included, the diluted oxide salt solution is introduced into an additive tank 16, and the ozone is added into the additive tank 16, and the ozone can sterilize the diluted oxide salt solution.

人體實驗 Human experiments

請參閱圖4A至4C,圖4A係為糖尿病足在未施用本發明水溶性氧化物傷口敷料時所拍攝之患部照片;圖4B係為糖尿病足在施用本發明水溶性氧化物傷口敷料2天後所拍攝之患部照片;以及圖4C係為糖尿病足在本發明施用水溶性氧化物傷口敷料7天後所拍攝之患部照片。 Please refer to Figures 4A to 4C. Figure 4A is a photograph of the affected part of a diabetic foot taken before the water-soluble oxide wound dressing of the present invention is applied; Figure 4B is a photograph of the affected part of a diabetic foot taken 2 days after the water-soluble oxide wound dressing of the present invention is applied; and Figure 4C is a photograph of the affected part of a diabetic foot taken 7 days after the water-soluble oxide wound dressing of the present invention is applied.

如圖4A至4C所示,測試者為一糖尿病足,該測試者的足肌腱韌帶組織已發生破潰,膿性分泌物及壞死組織增多。施用本發明水溶性氧化物傷口敷料於該病患的患部並觀察0至7天傷口癒合情形,該水溶性高分子的總重量百分比計包含:30.0%的海藻酸鈉、25.0%的聚乙烯吡咯烷酮及25.0%的羧甲基纖維素鈉,以100wt%該水溶性氧化物傷口敷料總重量百分比計算;在使用2天後潰瘍的情形改善,在使用7天後傷口慢慢癒合且傷口範圍縮小。 As shown in Figures 4A to 4C, the tester had diabetic foot, and the tendon ligament tissue of the tester had been ruptured, and purulent secretions and necrotic tissue increased. The water-soluble oxide wound dressing of the present invention was applied to the affected part of the patient and the wound healing was observed from 0 to 7 days. The total weight percentage of the water-soluble polymer included: 30.0% sodium alginate, 25.0% polyvinyl pyrrolidone and 25.0% sodium carboxymethyl cellulose, calculated based on 100wt% of the total weight percentage of the water-soluble oxide wound dressing; the ulcer situation improved after 2 days of use, and the wound slowly healed and the wound area was reduced after 7 days of use.

綜上所述,本發明的水溶性氧化物傷口敷料之製造方法所製成的水溶性氧化物傷口敷料使傷口處於濕性環境下,因此,傷口滲出液中的組織蛋白溶解酶,可促進壞死組織的溶解與吸收;低氧環境刺激毛細血管增生,有利於上皮細胞與膠原生成。其次,本發明的水溶性氧化物傷口敷料使傷口在封閉性保濕環境,敷料形成屏障感染機會下降,密閉狀態下的微酸環境,抑制細菌生長,有利於白細胞繁殖及發揮功能。再者,本發明的水溶性氧化物傷口敷料有助於保 留在創面中的滲液釋放並啟動多種酶和酶的活化因數,滲液還能有效地維持細胞的存活,促進多種生長因數的釋放刺激細胞增殖。藉此,本發明的水溶性氧化物傷口敷料具有抗炎性反應及傷口平整功效,進而可達到加速傷口癒合的目的。 In summary, the water-soluble oxide wound dressing produced by the manufacturing method of the water-soluble oxide wound dressing of the present invention puts the wound in a humid environment, so the tissue protein lytic enzyme in the wound exudate can promote the dissolution and absorption of necrotic tissue; the hypoxic environment stimulates the proliferation of capillaries, which is beneficial to the formation of epithelial cells and collagen. Secondly, the water-soluble oxide wound dressing of the present invention puts the wound in a closed and moisturizing environment, and the dressing forms a barrier to reduce the chance of infection. The slightly acidic environment in a closed state inhibits bacterial growth and is beneficial to the reproduction and function of white blood cells. Furthermore, the water-soluble oxide wound dressing of the present invention helps to release the exudate retained in the wound surface and activate various enzymes and enzyme activation factors. The exudate can also effectively maintain cell survival and promote the release of various growth factors to stimulate cell proliferation. Thus, the water-soluble oxide wound dressing of the present invention has anti-inflammatory reaction and wound smoothing effects, thereby achieving the purpose of accelerating wound healing.

惟以上所述僅為本發明之較佳實施例,非意欲侷限本發明的專利保護範圍,故舉凡運用本發明說明書及圖式內容所為的等效變化,均同理皆包含於本發明的權利保護範圍內,合予陳明。 However, the above is only a preferred embodiment of the present invention and is not intended to limit the scope of patent protection of the present invention. Therefore, all equivalent changes made by using the contents of the present invention's specification and drawings are also included in the scope of patent protection of the present invention and are hereby stated.

11:容置槽 11: Storage tank

12:活性碳吸附濾心 12: Activated carbon adsorption filter

13:電解磁化裝置 13: Electrolytic magnetization device

14:流量控制閥 14: Flow control valve

15:磁化反應器 15:Magnetic Reactor

151:水溶性高分子 151: Water-soluble polymer

Claims (10)

一種水溶性氧化物傷口敷料之製造方法,該方法包含如下步驟:提供一蒸餾水或一礦泉水;加入一氧化物鹽類水溶液於該蒸餾水或該礦泉水中以形成一稀釋氧化物鹽類水溶液,其中,該氧化物鹽類水溶液係透過一加熱電解法將一高壓氧通入一結晶鹽水溶液而形成,該氧化物鹽類水溶液具有約5.5至8之pH值及5~50mol/L的體積莫爾濃度,且該加熱電解法的加熱溫度控制在40~80℃之間;將該稀釋氧化物鹽類水溶液通過一活性碳吸附濾心以去除微量疏水性有害物質;以及通過一流量控制閥將該稀釋氧化物鹽類水溶液導入一磁化反應器中以進行一合成反應,且該磁化反應器具有一0.1到1特斯拉的磁場及一10到100伏特/厘米的電場,該磁化反應器的一合成溫度控制介於10℃至55℃之間,一合成壓力控制介於6kg/cm2至9kg/cm2之間的高壓,一合成時間為30~90分鐘,以形成一濃縮活性氧化物水;將該濃縮活性氧化物水加熱至65~70℃,加入一水溶性高分子及該蒸餾水或該礦泉水並攪拌3.5~4.5小時,攪拌轉速控制在600~650轉/分,再於真空狀態下攪拌5~6小時,以形成一水溶性氧化物傷口敷料;其中,該水溶性氧化物傷口敷料包含:45.0~55.0%的該蒸餾水或該礦泉水、15.0~25.0%的氧化物鹽類水溶液及30.0~35.0%的水溶性高分子,以該水溶性氧化物傷口敷料的總重量百分比計。 A method for manufacturing a water-soluble oxide wound dressing comprises the following steps: providing a distilled water or a mineral water; adding an oxide salt aqueous solution into the distilled water or the mineral water to form a dilute oxide salt aqueous solution, wherein the oxide salt aqueous solution is formed by passing a high-pressure oxygen into a crystalline salt aqueous solution through a heating electrolysis method, the oxide salt aqueous solution has a pH value of about 5.5 to 8 and a volume molar concentration of 5 to 50 mol/L, and the heating temperature of the heating electrolysis method is The temperature of the dilute oxide salt aqueous solution is controlled between 40 and 80° C.; the dilute oxide salt aqueous solution is passed through an activated carbon adsorption filter to remove trace hydrophobic harmful substances; and the dilute oxide salt aqueous solution is introduced into a magnetizing reactor through a flow control valve to perform a synthesis reaction, and the magnetizing reactor has a magnetic field of 0.1 to 1 Tesla and an electric field of 10 to 100 volts/cm, a synthesis temperature of the magnetizing reactor is controlled between 10° C. and 55° C., and a synthesis pressure is controlled between 6 kg/cm 2 to 9 kg/ cm2 , a synthesis time of 30 to 90 minutes to form a concentrated active oxide water; the concentrated active oxide water is heated to 65 to 70°C, a water-soluble polymer and the distilled water or the mineral water are added and stirred for 3.5 to 4.5 hours, the stirring speed is controlled at 600 to 650 rpm, and then stirred for 5 to 6 hours under a vacuum state to form a water-soluble oxide wound dressing; wherein the water-soluble oxide wound dressing comprises: 45.0 to 55.0% of the distilled water or the mineral water, 15.0 to 25.0% of an aqueous solution of oxide salts and 30.0 to 35.0% of the water-soluble polymer, based on the total weight percentage of the water-soluble oxide wound dressing. 如申請專利範圍第1項所述之水溶性氧化物傷口敷料之製造方法,其中,該氧化物鹽類水溶液具有10~40mol/L的體積莫爾濃度。 A method for manufacturing a water-soluble oxide wound dressing as described in Item 1 of the patent application, wherein the oxide salt aqueous solution has a volume molar concentration of 10-40 mol/L. 如申請專利範圍第1項所述之水溶性氧化物傷口敷料之製造方法,其中,該水溶性高分子係為海藻酸鈉、聚乙烯吡咯烷酮、羧甲基纖維素鈉、 透明質酸或其任意組合。 The method for manufacturing a water-soluble oxide wound dressing as described in item 1 of the patent application, wherein the water-soluble polymer is sodium alginate, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, hyaluronic acid or any combination thereof. 如申請專利範圍第3項所述之水溶性氧化物傷口敷料之製造方法,其中,該水溶性高分子包括:1.0~30.0%的海藻酸鈉、1.0~25.0%的聚乙烯吡咯烷酮及1.0~25.0%的羧甲基纖維素鈉,以該水溶性氧化物傷口敷料的總重量百分比計。 The method for manufacturing a water-soluble oxide wound dressing as described in item 3 of the patent application, wherein the water-soluble polymer comprises: 1.0-30.0% sodium alginate, 1.0-25.0% polyvinyl pyrrolidone and 1.0-25.0% sodium carboxymethyl cellulose, calculated as a percentage of the total weight of the water-soluble oxide wound dressing. 如申請專利範圍第1項所述之水溶性氧化物傷口敷料之製造方法,更包括一加入添加劑步驟,將該稀釋氧化物鹽類水溶液導入至一添加劑槽中,並將臭氧加入至該添加劑槽中以進行殺菌。 The method for manufacturing a water-soluble oxide wound dressing as described in item 1 of the patent application further includes a step of adding an additive, introducing the diluted oxide salt aqueous solution into an additive tank, and adding ozone into the additive tank for sterilization. 如申請專利範圍第1項所述之水溶性氧化物傷口敷料之製造方法,其中,該氧化物鹽類水溶液由一金屬元素陽離子與碳酸根、硫酸根、鉻酸根、鎢酸根、鉬酸根、磷酸根、砷酸根或釩酸根相互化合所構成的水溶液。 The method for manufacturing a water-soluble oxide wound dressing as described in item 1 of the patent application, wherein the oxide salt aqueous solution is an aqueous solution composed of a metal element cation and a carbonate, sulfate, chromate, tungstate, molybdate, phosphate, arsenate or vanadate. 如申請專利範圍第6項所述之水溶性氧化物傷口敷料之製造方法,其中,該金屬元素陽離子包括至少一種二價或三價金屬陽離子,其係為Fe2+、Cu2+、Zn2+、Pb2+、Mn2+、Bi3+或其任意組合。 A method for manufacturing a water-soluble oxide wound dressing as described in item 6 of the patent application, wherein the metal element cation includes at least one divalent or trivalent metal cation, which is Fe 2+ , Cu 2+ , Zn 2+ , Pb 2+ , Mn 2+ , Bi 3+ or any combination thereof. 如申請專利範圍第1項所述之水溶性氧化物傷口敷料之製造方法,其中,該水溶性氧化物傷口敷料厚度為0.1mm以上且4mm以下。 A method for manufacturing a water-soluble oxide wound dressing as described in Item 1 of the patent application, wherein the thickness of the water-soluble oxide wound dressing is greater than 0.1 mm and less than 4 mm. 如申請專利範圍第1項所述之水溶性氧化物傷口敷料之製造方法,其中,該流量控制閥將該稀釋氧化物鹽類水溶液之流速控制為500~8000L/min。 As described in item 1 of the patent application scope, the method for manufacturing a water-soluble oxide wound dressing, wherein the flow control valve controls the flow rate of the diluted oxide salt aqueous solution to 500~8000L/min. 一種如申請專利範圍第1至9項中任一項所述之製造方法所製得之水溶性氧化物傷口敷料。 A water-soluble oxide wound dressing produced by the manufacturing method described in any one of items 1 to 9 of the patent application scope.
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CN115645598A (en) 2022-09-30 2023-01-31 曼秀雷敦(中国)药业有限公司 Hydrocolloid dressing and preparation method thereof

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