200841880 九、發明說明： 【發明所屬之技術領域】 本發明屬於西藥製劑的技術領域，涉及一種治療燒燙傷的藥劑，特別涉及一 觀劑形態基於一氧化氮的新型高效燒烫讎藥劑及其製備方法。 [先前技術] 燒燙傷無論在和平時期和戰爭時期都是常見創傷。據醫學情報統計，我國在和 平時期每年因各種原因發生的燒燙傷患者約占總人口的千分之七到千分之十。隨著 社會的人們生活水準、物質文明的提高，摩托車的普及，免洗餐具茶具的使用，致 燒燙傷更易發生。 目前市面上的燒傷類藥品參差不齊，且治療時間較長，療效較慢。外用藥物治療在 燒傷治療中佔有首要突出地位，中醫及中藥製劑治療燒烫傷目前在市場上應用較爲 廣泛，但藥理和藥效都沒有準確的定位。燒傷的西藥治療主要是使用抗生素來控制 感染。其中使用最廣的當屬磺胺嘧啶銀，它的抗菌作用對控制倉腼感染雖有顯著效 果，但對細胞的活性亦有一定的損害作用，特別是使用高濃度的磺胺嘧啶銀糊劑或 混懸劑，有使創面損害加深之嫌。 一氧化氮爲一種雙原子分子，是很多生物功能的內生生理介體。自從1987年發現 哺乳動物血管內皮細胞能合成內源性一氧化氮以來，一氧化氮這個簡單的雙原子分 子自由基便開始向世人展示其無窮的魅力，被美國《科學》（《Science》）雜誌 評爲1992年的“明星分子”（Molecule of the Year)。一氧化氮除在心血管疾病、 腫瘤的治療等方面發揮作用外，其在燒燙傷治療、創面的修復以及抑制瘢痕生成等 多方面具有獨特的功效。 一氧化氮是體內非特異性防禦反應系統的組成部分。一氧化氮對細菌、真菌、寄生 蟲、瘤細胞有殺傷作用，對體內的腫瘤細胞有毒性作用，但在其發揮免疫作用的同時， 對那些表達一氧化氮合成酶的細胞自身及其附近細胞也有毒性作用。 越來越多的硏究表明一氧化氮在傷口癒合中有著重要的作用。一氧化氮是中性粒細 胞、單核細胞和巨噬細胞遊出活性的抑制劑，對中性粒細胞、單核細胞和巨噬細胞 的趨化性有促進作用。這有利於中性粒細胞的浸潤，將壞死組織與正常組織分隔開， 爲創面修復創造條件。一氧化氮還可以調節血管的口徑和流量，對肉芽組織中新生 200841880 血管提供充足的血液灌流，有利於新生血管的生長。其他作用可能包括：（1) 一氧 化氮調節炎症誘導水腫的形成，抑制細胞滲出而形成肉芽腫。⑵在傷口的癒合中 起作用的不僅僅是iNOS，eNOS (內皮型一氧化氮合酶）也被證實對傷口的癒合有作 用。(3)在體外的硏究中發現，來源於瘢痕疙瘩和肥厚性瘢痕的纖維母細胞表達少 量的eNOS刺激了細胞的高度再生功能。在創傷癒合中傷口的收縮是傷口閉合的一 個關鍵因素，實驗表明對一氧化氮合酶的抑制可延遲傷口的閉合，離體實驗同時也 證明了一氧化氮可以促進角化細胞的移動，對傷口的癒合有一定的促進作用。 Christian等在傷口癒合的動物模型中對中性粒細胞趨化的巨噬細胞炎症蛋白 (MIP-2)和單核細胞趨化的MCP21的動力學表現的硏究中發現，抑制一氧化氮合 酶可導致皮膚傷口的組織再生損害，其可能機制是擾亂了白細胞的浸潤而參與到傷 ^ 口的癒合讎。 隨著人們對一氧化氮在創傷傷口癒合作用的硏究，與一氧化氮相關的促進傷口癒合 的治療方法的硏究也有了很大的發展。臨床上對亞硝酸鈉與維生素C的應用可以 提高一氧化氮含量，對創傷癒合有一定的作用，但用法及用量上還比較混亂，過高的 一氧化氮含量和高酸的情況下可導致進一步的損傷和潰瘍的形成。 目前高濃度的精氨酸的補充治療作爲一種增加傷口內的一氧化氮合成來促進傷口 癒合的方法已經在臨床上開始應用。Bauer等硏究在實驗動物上利用敷有可產生一 氧化氮的藥物敷料對傷口進行治療，可以明顯促進傷口的癒合。一種與一氧化氮的 釋放同時應用的非甾體類藥品(NSAID)在動物實驗上經硏究可增膨原蛋白的合成， • 從而促進創傷傷口的癒合，而在單獨應用NSAID時膠原蛋白合成減少，傷口癒合緩 慢。Hardwick等利用具有可滲透性和親水性的聚酯共聚物膜，介於創傷傷口和可生 成一氧化氮的藥品之間，發現與局部用藥相比可有血管擴張的作用，另外在低濃度 時還可殺滅金黃色蔔萄球菌和大腸桿菌，在有缺血及感染的傷口中有很好的作用。 儘管目前人們對一氧化氮在創傷傷口癒合作用的硏究，與一氧化氮相關的促進傷口 癒合的治療方法的硏究都取得了較大進展，但在使用現有技術過程中，所用藥劑在 促進創傷傷口上皮細胞生成、抗菌消炎和促進皮膚的微循環，增進創傷傷口血管生 成等方面效果仍不太理想。 【發明內容】 針對現有技術的不足，本發明的目的在於提供一種治療燒燙傷的藥劑，即基於一氧 5 200841880 化氮的新型高效燒烫傷類貼劑。使該貼劑療效_切迅速，使用方便。與現有技術相比， 能進一步促進創傷傷口上皮細胞生成、抗菌消獒和促進皮膚的微循環，增進創傷傷□血 管生成等。 本發明涉及一種一氧化氮的局部釋放技福這種方法是由亞硝酸鹽，一種還原試劑 和一種弱酸結合而成。這種弱酸有足夠的酸性象引起亞硝酸鹽從一氧化氮中分離（PKa 介於大約1和4之間）。這些成分結合於一麵|^!1擴散的介質中，這種介質能有效的控 制一氧化氮擴散率並對局部使用有從凰粘性欠當然抗壞血酸維生素C或者抗壞血酸鹽 是首選，也可使用其他的合適的還原試劑例如尥-生育酚（維生素E)。在本發明中， 將三種試劑分佈在兩種凝膠基質中，作爲產生和控制一氧化氮擴散率的成分。從這方面 來說，氮劑凝膠體中只包含了亞硝酸鹽，而^劑凝膠體則包含了有足夠酸性的酸，用來 將亞硝酸鹽從一氧化氮中分離出來。 在酸劑凝膠中更適合含有一種用來幫助保_處於生物活注形態的一氧化氮的還原 試劑。人們更傾向於使用的還原製劑是抗壞血酸維生素C (維他命C )。酸劑凝膠中的酸 最好是檸檬酸，當然無機酸也可能適用，例如_酸。凝膠化製劑包含例如:羥乙基纖維 素’瓊脂和矽酸等的物質。人們更傾向於使用_亞硝酸鹽是亞硝酸鈉，雖然其他的亞硝 酸鹽也可以使用。 本發明是以如下技術方案實現的： 本發明是一種基於一氧化氮的新型高效燒變傷類貼劑，由膠帶和塗布在基質上的氮 劑和酸劑構成。當氮劑和酸劑相結合，便可以_部可控制的釋放有效成分---氧化 氮。所說的基質爲一種載體，可以採用多種材料，如透氣性的聚酯類高分子材料、聚;^ 烴類高分子材料，布或者膠紙等。 (1)本發明的新型高效燒燙傷類貼劑的製備遍法，包括以下步驟： a.亞硝酸鹽中加入適量蒸餾水，使之充分溶解後加入凝膠化製劑，在室溫下擾動， 然後靜置至凝膠清澈，製備成氮劑雜。 其中，亞硝酸鹽優選亞硝酸鈉； 凝膠化製劑選自：羥乙基纖維素、瓊或矽酸等物質，最優選2—經乙基纖維素。 b·氮劑凝膠緩緩通過塗布設備，氮劑被均勻地塗布在聚酯類高分子材料、聚嫌烴 類高分子材料 '紗布或者膠紙的基質上，基質優選透氣性@ ,分切，製備成氮 劑貯藥層備用。 6 200841880 氮劑凝膠也可緩緩通過設備，裝塡於密封袋或小塑膠膠管中備用。 C·在酸劑和還原劑中加入蒸餾水，使之充分溶解後加入凝膠化製劑，在室溫下攪 動，然後靜置至凝膠清澈，製備成酸劑凝膠；其中，酸劑爲檸檬酸或硼酸，更 優選檸檬酸;還原劑爲抗壞血酸維生素C或者α-生育酸維生素E，更優選抗壞 血酸維生素C ·，凝膠化製劑選自：羥乙基纖維、瓊脂或砍酸等物質，最優選2-羥乙基纖維素；亞硝酸鹽、酸劑與還原劑三者用量摩爾比爲1 : 1 : 1。 d·酸劑凝膠緩緩通過塗布設備，酸劑被均句地塗布在聚酯類筒分子材料、聚嫌烴 類高分子材料、紗布或者膠紙的基質上，基質優選透氣性的，分切，製備成酸 劑貯藥層備用。 以上步驟中，氮劑凝膠和酸劑凝膠的製備過程不分先後。 (2 )貼劑製作工藝和用法用量 三種貼劑類型分別採用不同的製作流程和使用方法： I型： 製作流程:整個貼劑呈“T〃字形，分爲兩部分，AffiB 〇其中A部分底部爲膠帶 層，可以採用PVP膠帶、彈力布、氧化鋅膠布或者PU膠帶。在膠帶層中央爲酸劑貯 藥層，是將配置好的酸劑凝膠塗布在基質上，基質可以採用多種材料，如透氣性的 聚酯類高分子材Μ'聚烯烴類高分子材布或者膠紙等°覆蓋層是兩條以不乾 膠布爲材料製成的，它們向外的一端與膠帶層的裸露部分粘貼，向內的一端可以覆 蓋住酸劑貯藥層。Β部分是氮劑貯藥層和上下兩層覆蓋層。氮劑貯藥層是將配置好 的氮劑凝膠塗布在同樣的基質上。 用法用量：清潔創面，將貼劑的防粘膠紙撕下，氮劑貯藥層對折並覆胃#_胃 貯藥層上，將氮劑貯藥層貼於創面，鬆緊適當即可。 Π型 製作流程：II型包括貼劑Α和附件Β 〇其中Α部分爲長方形，底部爲膠帶層，可 以採用PVP膠帶、彈力布、氧化鋅膠布或者PU膠帶。在膠帶層中央爲酸劑貯藥層， 是將配置好的酸劑凝膠塗布在基質上，基質可以採用多種材料，如透氣性的聚酯類 高分子材料 '聚胃胃#·?#料' &等。胃蓋層是兩條以不乾膠布爲 材料製成，它們向外的一端與膠帶層的裸露部分粘貼，向內的一端可以覆蓋住酸劑 貯藥層。附件B爲小正方形密封袋，可採用常規的密封袋，內置配置好的氮劑凝膠。 7 200841880 用法用量：清潔創面，從防貼膠紙上揭下貼劑，打開小密封袋，將其內的凝膠 均勻地塗布在酸劑貯藥層後，讓藥物層貼於倉腼，鬆緊適當即可。 m型 製作流程:類似於II型，包括貼劑A和附件B。其中貼劑A的製備流程同II型一致； 附件B爲小塑膠膠管，內含配置好的氮劑凝膠，並用蓋子旋緊。 用法用量··清潔創面，從防貼膠紙上揭下貼劑，打開小塑膠膠管，將其內的凝 膠均勻地塗布在酸劑貯藥層後，讓藥物層貼於創面，鬆緊適當即可。 (3) 使用注意事項： 在使臓類型貼劑時’將酸劑凝膠和氮劑凝膠接觸 > 並儘量保證酸劑凝膠近外界， 氮劑凝膠近皮膚。這是因爲： a·酸劑凝膠和氮劑凝膠接觸後便可在局部釋放一氧化氮，避免細菌感染，達到消 炎、提高皮膚局部免疫力，促進傷口癒合和皮膚再生的功能。 b·由於酸劑凝膠近外界，酸劑凝膠具有還原能力，降低了新產生的一氧化氮被氧化 的可能性。 (4) 貯藏：密閉，置陰涼乾燥處保存。 與現有的燒烫傷類產品、創可貼類產品相比，本發明具有以下的獨特功效： 1 ·一氧化氮分子同時具備殺菌、消炎、提高肌體免疫力、促進傷口癒合和皮膚再生多 種功效。 2·使用酸劑凝膠和氮劑凝膠相接觸局部產生一氧化氮，將一氧化氮首次用於燒燙傷的 ^ 治療上。該方法克服了已有的燒燙傷類產品治療時間較長，療效較慢的缺點，迅速釋放 的一氧化氮能夠及時緩解症狀，且不存在副作用。 3·由於酸劑凝膠近外界，氮劑凝膠近皮膚，有效的解決了生成的一氧化氮被氧化的可 能性。 4·將創可貼與治療燒燙傷藥劑相結合。創可貼型具有一定屏障功能，減少因倉腼裸露 弓1發的倂發症，減少創面疼痛，同時可爲倉_提供一個濕潤的環真加速上皮再生。其 最大的優勢在於易於更換，吸水性強，可防止創面積液感染，可減少供皮區疼痛，促進 表皮化，無感染，無明顯瘢痕形成。 經藥理實驗證實，3S於一氧化氮的新型高效燒燙傷類貼劑原料可有效地治療1、2 級燒燙傷，加速皮膚的癒合。 8 200841880 卜抗菌消炎:表1是分別使用現有技術和本發明的發炎細胞（占傷口面積百分比）與時 間的關係的對比，表明使用本發明的凝膠貼劑的顯著抗菌消炎作用： 表1200841880 IX. Description of the invention: [Technical field of invention] The invention belongs to the technical field of western medicine preparations, and relates to a medicament for treating burns and burns, in particular to a novel high-efficiency scald sputum agent based on nitric oxide and preparation thereof method. [Prior Art] Burns and burns are common traumas in peacetime and wartime. According to medical intelligence statistics, in the country during the peace period, the number of patients suffering from burns and burns for various reasons each year accounts for about seven-tenths of a thousandth of the total population. With the improvement of people's living standards and material civilization in the society, the popularity of motorcycles and the use of disposable tableware and tea sets are more likely to occur. At present, the burn drugs on the market are uneven, and the treatment time is longer, and the curative effect is slower. External drug treatment plays a leading role in the treatment of burns. Traditional Chinese medicine and traditional Chinese medicine preparations are widely used in the market for the treatment of burns and burns, but there is no accurate positioning of pharmacology and efficacy. Western medicine for burns mainly uses antibiotics to control infection. Among them, the most widely used is sulfadiazine silver, its antibacterial effect has a significant effect on the control of Cangjie infection, but also has a certain damage to the activity of cells, especially the use of high concentration of sulfadiazine silver paste or mixed Suspension, it is suspected of deepening wound damage. Nitric oxide is a diatomic molecule that is an endogenous physiological mediator of many biological functions. Since the discovery of mammalian vascular endothelial cells capable of synthesizing endogenous nitric oxide in 1987, nitric oxide, a simple diatomic molecular free radical, has begun to show its infinite charm to the world, and it has been "Science" by the United States. The magazine was named "Molecule of the Year" in 1992. In addition to its role in the treatment of cardiovascular diseases and tumors, nitric oxide has unique effects in the treatment of burns, wound repair, and inhibition of scar formation. Nitric oxide is an integral part of the in vivo non-specific defense response system. Nitric oxide has a bactericidal effect on bacteria, fungi, parasites, and tumor cells, and has toxic effects on tumor cells in the body, but at the same time as its immune function, cells expressing nitric oxide synthase itself and nearby cells It also has toxic effects. More and more research shows that nitric oxide plays an important role in wound healing. Nitric oxide is an inhibitor of neutrophil, monocyte and macrophage migration activity, and promotes the chemotaxis of neutrophils, monocytes and macrophages. This facilitates the infiltration of neutrophils, separating the necrotic tissue from the normal tissue and creating conditions for wound repair. Nitric oxide can also regulate the diameter and flow of blood vessels, and provide sufficient blood perfusion to the new 200841880 blood vessels in granulation tissue, which is conducive to the growth of new blood vessels. Other effects may include: (1) Nitric oxide regulates inflammation-induced edema formation and inhibits cell exudation to form granulomas. (2) It is not only iNOS that acts in the healing of wounds, but also eNOS (endothelial nitric oxide synthase) has been shown to have an effect on wound healing. (3) In vitro studies revealed that the expression of a small amount of eNOS by fibroblasts derived from keloids and hypertrophic scars stimulated the highly regenerative function of the cells. The contraction of wounds in wound healing is a key factor in wound closure. Experiments have shown that inhibition of nitric oxide synthase can delay the closure of wounds. Ex vivo experiments also demonstrate that nitric oxide can promote the movement of keratinocytes. The healing of the wound has a certain promoting effect. Christian et al. found in the animal model of wound healing that the neutrophil chemoattractant macrophage inflammatory protein (MIP-2) and monocyte chemotactic MCP21 kinetics showed inhibition of nitric oxide Enzymes can cause tissue regeneration damage in skin wounds, and the possible mechanism is to disturb the infiltration of white blood cells and participate in the healing of the wounds. With the study of the role of nitric oxide in the healing of wound wounds, the research on the treatment of wound healing associated with nitric oxide has also been greatly developed. Clinical application of sodium nitrite and vitamin C can increase the content of nitric oxide and have a certain effect on wound healing, but the usage and dosage are still confusing. Excessive levels of nitric oxide and high acid can lead to Further damage and ulcer formation. The current high-concentration arginine supplementation therapy has been applied clinically as a method to increase nitric oxide synthesis in wounds to promote wound healing. Bauer et al. used a drug dressing with nitric oxide to produce wounds on experimental animals to significantly promote wound healing. A non-steroidal drug (NSAID) that is used in conjunction with the release of nitric oxide can be used in animal experiments to increase the synthesis of proinflammatory proteins, thereby promoting healing of wound wounds, and collagen synthesis in the application of NSAID alone. Reduced, the wound heals slowly. Hardwick et al. utilize a permeable and hydrophilic polyester copolymer membrane that is found to have vasodilatation compared to topical medications between wound wounds and nitric oxide-producing drugs, and at low concentrations It also kills Staphylococcus aureus and Escherichia coli and has a good effect in wounds with ischemia and infection. Despite the current research on the role of nitric oxide in the healing of wound wounds, and the research on the treatment of nitric oxide-related wound healing, great progress has been made, but in the process of using the prior art, the agents used are promoting The effects of wound wound epithelial cell production, antibacterial and anti-inflammatory, and promoting microcirculation of the skin and promoting vascularization of wounds and wounds are still not satisfactory. SUMMARY OF THE INVENTION In view of the deficiencies of the prior art, an object of the present invention is to provide a medicament for treating burns and burns, that is, a novel high-efficiency burn-in-type patch based on nitrogen oxides of 200841880. The effect of the patch is rapid and easy to use. Compared with the prior art, it can further promote the formation of wound wound epithelial cells, antibacterial elimination and promote microcirculation of the skin, and promote blood vessel formation of wounds and wounds. The present invention relates to a partial release technique of nitric oxide. This method is a combination of nitrite, a reducing agent and a weak acid. This weak acid is sufficiently acidic to cause the nitrite to separate from nitric oxide (with a PKa between about 1 and 4). These ingredients are combined in a medium that diffuses |^!1. This medium can effectively control the diffusion rate of nitric oxide and is used for topical use. It is preferred that ascorbic acid ascorbate or ascorbate is preferred. Others can also be used. Suitable reducing agents such as guanidine-tocopherol (vitamin E). In the present invention, three reagents are distributed in two gel matrices as components for generating and controlling the diffusion rate of nitric oxide. In this respect, the nitrogen gel contains only nitrite, and the gel contains a sufficiently acidic acid to separate the nitrite from nitric oxide. It is more suitable in an acid gel to contain a reducing agent for helping to maintain nitric oxide in a bioactive form. The reducing agent that people prefer to use is ascorbate vitamin C (vitamin C). The acid in the acid gel is preferably citric acid, although inorganic acids may also be suitable, such as _acid. The gelled preparation contains, for example, a substance such as hydroxyethyl cellulose 'agar and citric acid. People prefer to use nitrite as sodium nitrite, although other nitrites can be used. The present invention is achieved by the following technical solution: The present invention is a novel high-efficiency burn-in-type patch based on nitric oxide, which is composed of a tape and a nitrogen agent and an acid agent coated on a substrate. When the nitrogen agent and the acid agent are combined, the active ingredient, nitrogen oxide, can be released in a controlled manner. The substrate is a carrier, and various materials such as a gas permeable polyester polymer material, a polyhydrocarbon polymer material, a cloth or a tape, and the like can be used. (1) The preparation method of the novel high-efficiency burn-type patch of the present invention comprises the following steps: a. adding an appropriate amount of distilled water to the nitrite, fully dissolving it, adding the gelled preparation, disturbing at room temperature, and then The mixture was allowed to stand until the gel was clear, and a nitrogen agent was prepared. Among them, the nitrite is preferably sodium nitrite; the gelation preparation is selected from the group consisting of hydroxyethyl cellulose, agar or citric acid, and most preferably 2-ethyl cellulose. b. Nitrogen gel slowly passes through the coating equipment, and the nitrogen agent is uniformly coated on the polyester polymer material, the polysulfide polymer material 'gauze or the matrix of the adhesive tape, and the matrix is preferably breathable @, slitting Prepare a nitrogen storage layer for use. 6 200841880 Nitrogen gel can also be slowly passed through equipment and packed in sealed bags or small plastic hoses for use. C. adding distilled water to the acid agent and the reducing agent, fully dissolving it, adding the gelation preparation, stirring at room temperature, and then standing still until the gel is clear to prepare an acid gel; wherein the acid agent is lemon Acid or boric acid, more preferably citric acid; reducing agent is ascorbic acid vitamin C or α-tocopherol vitamin E, more preferably ascorbic acid vitamin C ·, gelling agent is selected from the group consisting of: hydroxyethyl fiber, agar or chopping acid, etc. Preferably, the 2-hydroxyethyl cellulose; the nitrite, the acid agent and the reducing agent are used in a molar ratio of 1:1:1. d. The acid gel is slowly passed through the coating device, and the acid agent is uniformly coated on the matrix of the polyester tube molecular material, the polyhydrocarbon polymer material, the gauze or the adhesive tape, and the substrate is preferably gas permeable. Cut, prepare the acid storage layer for use. In the above steps, the preparation process of the nitrogen gel and the acid gel is in no particular order. (2) Patch preparation process and usage and dosage The three types of patch use different production processes and usage methods: Type I: Production process: The whole patch is “T〃 shape, divided into two parts, AffiB 〇 part A bottom For the tape layer, PVP tape, elastic cloth, zinc oxide tape or PU tape can be used. In the middle of the tape layer, the acid storage layer is coated on the substrate, and the substrate can be made of various materials. For example, the gas-permeable polyester polymer material 聚烯烃 'polyolefin polymer cloth or adhesive tape, etc., the cover layer is made of two kinds of self-adhesive tapes, and the outward end and the bare part of the tape layer. Paste, the inward end can cover the acid reservoir layer. The Β part is the nitrogen reservoir layer and the upper and lower coating layers. The nitrogen reservoir layer is coated with the formulated nitrogen agent on the same substrate. Usage and dosage: Clean the wound surface, tear off the anti-adhesive paper of the patch, fold the nitrogen storage layer and cover the stomach #_ stomach storage layer, stick the nitrogen storage layer on the wound surface, and tighten it properly. Π type production process: Type II includes patch Α Attachment Β 〇 The Α part is rectangular, the bottom is tape layer, you can use PVP tape, elastic cloth, zinc oxide tape or PU tape. In the middle of the tape layer is the acid storage layer, which is coated with acid gel. On the substrate, the substrate can be made of various materials, such as a gas permeable polyester polymer material 'Juweiwei #·?#料' & etc. The gastric cap layer is made of two kinds of self-adhesive cloth materials, they The outward end is pasted with the exposed portion of the tape layer, and the inward end covers the acid reservoir. The accessory B is a small square sealed bag that can be sealed with a conventional sealed bag and a built-in nitrogen gel. 200841880 Dosage: Clean the wound, remove the patch from the anti-adhesive paper, open the small sealed bag, and evenly coat the gel inside the acid storage layer, let the drug layer stick to the cartridge, and tighten it properly. M-type production process: similar to type II, including patch A and accessory B. The preparation process of patch A is the same as type II; accessory B is a small plastic hose containing the configured nitrogen gel and used The lid is tightened. Usage and dosage · · Clean Face, remove the patch from the anti-adhesive tape, open the small plastic hose, and evenly apply the gel inside the acid storage layer, let the drug layer stick to the wound surface, and tighten it properly. (3) Use Note: When making the sputum type patch, 'contact the acid gel with the nitrogen gel> and try to ensure that the acid gel is close to the outside, and the nitrogen gel is close to the skin. This is because: a·acid condensate After contact with the gel and the nitrogen gel, it can release nitric oxide locally, avoid bacterial infection, achieve anti-inflammatory, improve local immunity of the skin, and promote wound healing and skin regeneration. b·Because the acid gel is close to the outside, acid The agent gel has reducing ability and reduces the possibility of newly generated nitric oxide being oxidized. (4) Storage: sealed, stored in a cool dry place. Compared with existing burnt products and band-aid products, this The invention has the following unique effects: 1 · Nitric oxide molecules have both bactericidal, anti-inflammatory, improved immunity, wound healing and skin regeneration. 2. Use an acid gel and a nitrogen gel to locally produce nitric oxide, and use nitric oxide for the first time for the treatment of burns. The method overcomes the shortcomings of the prior treatment of burned scald products and has a slow therapeutic effect, and the rapidly released nitric oxide can relieve the symptoms in time without side effects. 3. Since the acid gel is close to the outside, the nitrogen gel is close to the skin, effectively solving the possibility of the generated nitric oxide being oxidized. 4. Combine band-aid with therapeutic burns. The band-aid type has a certain barrier function, which reduces the hair loss caused by the naked bow of the squat, reduces the pain of the wound, and provides a moist ring for the _ _ _ _ Its biggest advantage is easy to replace, strong water absorption, can prevent infection of wound area, reduce pain in the donor area, promote epidermalization, no infection, no obvious scar formation. Pharmacological experiments confirmed that 3S new high-efficiency burn-and-burn patch materials for nitric oxide can effectively treat grade 1 and 2 burns and accelerate skin healing. 8 200841880 Antibacterial anti-inflammatory: Table 1 is a comparison of the relationship between inflammatory cells (% of wound area) and time of the prior art and the present invention, respectively, showing significant antibacterial and anti-inflammatory effects using the gel patch of the present invention: Table 1
間。 表2 間 上皮細胞生長\\ 3天 5天 10天 15天 現有技術 20. 0% 29. 0% 39. 5% 40. 2% 明 29. 0% 34. 0% 48. 0% 61.0% gjf的微循環：表3是分別使用現有技術和本發明的血管生成（占傷口總面積的百分 比）與時間的關係的對比，表明使用本發明的凝膠貼劑顯著使血管生成增加。between. Table 2 Interstitial cell growth \\ 3 days 5 days 10 days 15 days prior art 20. 0% 29. 0% 39. 5% 40. 2% 明 29. 0% 34. 0% 48. 0% 61.0% gjf Microcirculation: Table 3 is a comparison of angiogenesis (% of total wound area) versus time using prior art and the present invention, respectively, indicating that angiogenesis is significantly increased using the gel patch of the present invention.
表 3___________ 時間 3天 5天 10天 15天 血管生 現有技術 0. 3% 0. 6% 1.1% 1.5% 一明 〇. 7% 1.5% 3.1% 3. 3% 發炎細 3天 5天 10天 15天 現有技術 80.0% 50. 0% 20. 5% 10. 0% 本發明 72. 0% 34. 0% 10. 0% 7.0% 2 . 速傷口癒合:表2是分別使用現有技術和本發明的上皮細胞生長（占傷口尺寸的百 分比）與時間的關係的對比，表明使用本發明的凝膠貼劑能更加顯著縮短傷口癒合的時 附圖說明 圖1 :本發明實施例1的立體圖。 9 200841880 【實施方式】 以下結合說明書附圖對本發明做進一步的描述，實施例僅爲本發明的較佳實施例 而已，當不能以此限定本發明的範圍。即大凡依本發明申請專利範圍所作的均等變化 與修飾，皆應仍屬本發明專利涵蓋的範圍內。 實施例1 稱取亞硝酸鈉0·1克，加入50毫升蒸餾水，使之充分溶解後加入2-羥乙基纖維素 750，000 0.16克：在室溫的環境中不停的攪動6小時，然後靜置24小時直至凝膠清 澈，製備成氮劑凝膠。氮劑凝膠緩緩通過塗布設備，每2毫升氮劑被均勻地塗布在基 質上，基質採用透氣性的聚酯類高分子材料、聚烯烴類高分子材料、紗布或者膠紙等。 分切，製備成氮劑貯藥層備用。 稱取檸檬酸〇·31克，L(+)-抗壞血酸0·26克，加入50毫升蒸餾水，使之充分溶解後 加入2-羥乙基纖維素750，000 0.16克，在室溫的環境中不停的攪動3小時，然後靜置 24小時直至凝膠清澈，製備成酸劑凝膠。酸劑凝膠緩緩通過塗布設備，每2毫升酸劑 被均勻地塗布在基質上，基質可以採用多種材料，如透氣性的聚酯類高分子材料、聚 烯烴類高分子材料 '紗布或者膠紙等。分切，備成酸劑貯藥層備用d 成品如圖1所示，$1個貼劑呈“Τ"字形，分爲兩部分，Α和Β。其中Α部分底部爲膠 帶層（1)，可以採用PVP膠帶、彈力布、氧化鋅膠布或者PU膠帶。在膠帶層（；l )中 央爲酸劑貯藥層（2)。覆蓋層（3)是兩條以不乾膠布爲材料製成的，它們向外的一 端與膠帶層（1)的裸露部分粘貼，向內的一端可以覆蓋住酸劑貯藥層（2)。B部分是 氮劑貯藥層（4)和上下兩層覆蓋層(3)和⑸。 用法用量：清潔創面，將貼劑的防粘膠紙撕下，氮劑貯藥層對折並覆蓋在酸劑貯藥層 上，將氮劑貯藥層貼於創面，鬆緊適當即可。 實施例2 用與實施例1相同的方法製備新型高效燒烫傷類貼劑’但在製備過程中，氮劑凝 膠緩緩通過設備，每2毫升氮劑被分裝置於2釐米x2釐米的密封袋中，可採用常規的密 封袋，爲附件B 〇 成品包括貼劑（A)和附件（B)。其中A部分與實施例1的A部分相同，爲長方形， 底部爲膠帶層(1)，可以採用PVP膠帶、彈力布、氧化鋅膠布或者PU膠帶。在膠帶層 (1)中央爲酸劑貯藥層（2)，覆蓋層（3)是兩條以不乾膠布爲材料製成，它們向外 10 200841880 的一端與膠W層（1)的裸露部分粘貼，向內的一端可以覆蓋住酸劑貯藥層（2)。 构潔倉画，從防貼鱗氏上揭下貼劑，打開小密封袋，將其內的凝膠 均勻地全布在酸劑貯藥層後，讓藥物層貼於創面，鬆緊適當即可。 實施例3 用與實施例1相同的方法製備新型高效燒燙傷類貼劑，但在製備過程中，氮劑凝 ’ _2ig升氮劑被分裝置於3毫升的小塑膠膠管中，並用蓋子旋緊，作 爲附件B。 成品與實施例2相同。 用法用量··清潔創面，從防貼膠紙上揭下貼劑，打開小塑膠膠管，將其內的凝膠 均勻地塗布在酸劑貯藥層後，讓藥物層貼於創面，鬆緊適當即可。 • 實議4 用與實施例1相同的方法製備新型高效燒燙傷類貼劑，但在製備過程中，酸劑檸 檬酸〇·31克改爲硼酸〇,〇91g，其他條件不變。 實施例5 用與實施例1相同的方法製備新型高效燒燙傷類貼劑，但在製備過程中，還原劑抗 壞血酸維生素C改爲等摩爾量的α -生育酚（維生素E)，其他條件不變。 實施例6 用與實施例1相同的方法製備新型高效燒燙傷類貼劑，但在製備過程中，凝膠化 製劑2-羥乙基纖維素750，000改爲瓊脂，其他條件不變。 • 實施例7 用與實施例1相同的方法製備新型高效燒燙傷類貼劑，但在製備過程中，凝膠化製 劑2-羥乙基纖維素750，000改爲矽酸，其他條件不變。 【圖式簡單說明】 圖1爲本成品的圖型，整個貼劑呈“Τ”字形，分爲兩部分，Α和Β。其中Α部分底 部爲膠帶層⑴，可以採用PVP膠帶、彈力布、氧化鋅膠布或者PU膠帶。在膠帶層（1) 中央爲酸劑貯藥層（2)。覆蓋層〇)是兩條以不乾膠布爲材料製成的’它們向外的 一端與膠帶層（1)的ί果露部分粘貼，向內的一端可以覆蓋住酸劑貯藥層（2)。B部分 11 200841880 是氮劑貯藥層（4)和上下兩層覆蓋層⑶和⑸。 【主要元件符號說明】 A代表酸劑 B代表氮劑 ⑴爲膠帶層 (2) 酸劑貯藥層 (3) 覆蓋層 ⑷氮劑貯藥層 ⑸覆蓋層Table 3___________ Time 3 days 5 days 10 days 15 days Angiosthesis prior art 0. 3% 0. 6% 1.1% 1.5% Alum. 7% 1.5% 3.1% 3. 3% Inflamed fine 3 days 5 days 10 days 15 Days prior art 80.0% 50. 0% 20. 5% 10. 0% of the invention 72. 0% 34. 0% 10. 0% 7.0% 2. Speed wound healing: Table 2 is the use of the prior art and the present invention respectively Comparison of epithelial cell growth (percentage of wound size) versus time indicates that the use of the gel patch of the present invention can significantly shorten wound healing. FIG. 1 is a perspective view of Embodiment 1 of the present invention. The invention is further described in the following with reference to the accompanying drawings, which are merely preferred embodiments of the invention, and are not intended to limit the scope of the invention. That is, the equivalent changes and modifications made by the invention in accordance with the scope of the invention are still within the scope of the invention. Example 1 Weighed 0.11 g of sodium nitrite, added 50 ml of distilled water, and dissolved it sufficiently, and then added 2-hydroxyethyl cellulose to 750,000 0.16 g: stirring was continued for 6 hours in a room temperature environment. It was then allowed to stand for 24 hours until the gel was clear to prepare a nitrogen gel. The nitrogen gel is slowly passed through the coating apparatus, and each 2 ml of the nitrogen agent is uniformly applied to the substrate, and the substrate is made of a gas permeable polyester polymer material, a polyolefin polymer material, gauze or tape. Slitting, preparing a nitrogen storage layer for use. Weigh 31 g of bismuth citrate, 0. 26 g of L(+)-ascorbic acid, add 50 ml of distilled water, dissolve it sufficiently, and add 2-hydroxyethyl cellulose 750,000 0.16 g in a room temperature environment. The mixture was stirred for 3 hours, and then allowed to stand for 24 hours until the gel was clear to prepare an acid gel. The acid gel is slowly passed through the coating equipment, and every 2 ml of the acid agent is evenly coated on the substrate. The substrate can be made of various materials, such as a gas permeable polyester polymer material, a polyolefin polymer material, gauze or glue. Paper, etc. Slitting, preparation of acid storage layer spare d finished product as shown in Figure 1, $1 patch is "Τ", the font is divided into two parts, Α and Β. The bottom part of the 为 part is the tape layer (1), can Use PVP tape, elastic cloth, zinc oxide tape or PU tape. In the middle of the tape layer (; l) is the acid storage layer (2). The cover layer (3) is made of two kinds of self-adhesive tape. The outward end of the tape is adhered to the bare portion of the tape layer (1), and the inward end covers the acid reservoir layer (2). Part B is the nitrogen reservoir layer (4) and the upper and lower cover layers ( 3) and (5). Usage and dosage: Clean the wound surface, tear off the anti-adhesive paper of the patch, fold the nitrogen storage layer and cover it on the acid storage layer, and stick the nitrogen storage layer on the wound surface. Example 2 A new high-efficiency burn-in patch was prepared in the same manner as in Example 1 but in the preparation process, the nitrogen gel was slowly passed through the apparatus, and 2 ml of nitrogen was dispensed in 2 cm. In the sealed bag of x2 cm, a conventional sealed bag can be used, and the finished product including the patch (A) and the accessory (B) is included in the accessory B. It is the same as the part A of the embodiment 1, and has a rectangular shape, and the bottom is a tape layer (1), and a PVP tape, a stretch cloth, a zinc oxide tape or a PU tape can be used. In the middle of the tape layer (1), an acid storage layer ( 2), the cover layer (3) is made of two kinds of self-adhesive tapes, which are pasted to the bare part of the glue W layer (1) at the end of 10 200841880, and the inward end can cover the acid storage. Layer (2). Clean the warehouse painting, remove the patch from the anti-sticking scale, open the small sealed bag, and evenly distribute the gel inside the acid storage layer, and let the drug layer adhere to the wound surface. The elasticity is appropriate. Example 3 A new type of high-efficiency burn-in type patch is prepared in the same manner as in Example 1, but in the preparation process, the nitrogen agent is condensed into a small plastic hose of 3 ml. In the middle, and use the lid to tighten, as the accessory B. The finished product is the same as in Example 2. Usage and dosage ··Clean the wound, remove the patch from the anti-adhesive paper, open the small plastic hose, and evenly coat the gel inside After the acid reservoir is stored, let the drug layer stick to the wound surface and tighten it properly. 4 A new type of high-efficiency burn-in-type patch was prepared in the same manner as in Example 1, but in the preparation process, the acid agent bismuth citrate·31 g was changed to bismuth borate, 〇91 g, and other conditions were unchanged. Example 5 In the same manner as in Example 1, a new type of high-efficiency burn-in patch was prepared, but in the preparation process, the reducing agent ascorbic acid vitamin C was changed to an equimolar amount of α-tocopherol (vitamin E), and other conditions were unchanged. A new high-efficiency burn-in patch was prepared in the same manner as in Example 1, but in the preparation process, the gelled preparation of 2-hydroxyethylcellulose 750,000 was changed to agar, and other conditions were unchanged. A new high-efficiency burn-in patch was prepared in the same manner as in Example 1, but in the preparation process, the gelled preparation 2-hydroxyethylcellulose 750,000 was changed to tannic acid, and other conditions were unchanged. [Simple description of the diagram] Figure 1 shows the pattern of the finished product. The entire patch is in the shape of a "Τ", divided into two parts, Α and Β. The bottom part of the crucible is a tape layer (1), and a PVP tape, a stretch cloth, a zinc oxide tape or a PU tape can be used. In the center of the tape layer (1) is the acid reservoir layer (2). The cover layer is made of two kinds of self-adhesive tapes. 'The outer end of the cover layer is adhered to the lyophilized part of the tape layer (1), and the inward end can cover the acid reservoir layer (2) . Part B 11 200841880 is a nitrogen reservoir layer (4) and two upper and lower cover layers (3) and (5). [Main component symbol description] A stands for acid agent B stands for nitrogen agent (1) is tape layer (2) acid agent storage layer (3) coating layer (4) nitrogen agent storage layer (5) coating layer
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