CN117024607A - 一种用于抗菌的多肽药物及其应用 - Google Patents
一种用于抗菌的多肽药物及其应用 Download PDFInfo
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- CN117024607A CN117024607A CN202311213128.1A CN202311213128A CN117024607A CN 117024607 A CN117024607 A CN 117024607A CN 202311213128 A CN202311213128 A CN 202311213128A CN 117024607 A CN117024607 A CN 117024607A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
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Abstract
本发明公开了一种抗菌肽及其应用;其由细胞穿透肽X1与炎症抑制肽X2通过偶联获得;所述的细胞穿透肽X1的氨基酸序列为SEQ ID No.1‑SEQ ID No.8中的任意一种;所述的炎症抑制肽X2的氨基酸序列为SEQ ID No.9‑SEQ ID No.10中的任意一种;该抗菌肽可以用于抑制普通感染和一些顽固性感染,可以用于替代抗生素在抗感染领域加以应用,可以解决日益严重的抗生素耐药性问题。
Description
技术领域
本发明涉及多肽技术领域,特别是一种新型抗菌肽及其在抑制炎症领域内的应用。
背景技术
抗生素是由微生物(包括细菌、真菌、放线菌属)或高等动植物在生活过程中所产生的具有抗病原体或其他活性的一类次级代谢产物,能干扰其他生活细胞发育功能的化学物质。它不仅能杀灭细菌,而且对霉菌、支原体、衣原体、螺旋体、立克次氏体等其他致病微生物也有良好的抑制和杀灭作用。
自1928年英国科学家弗莱明发现了第一个抗生素一一青霉素以来,人类暂时摆脱了细菌性感染传染疾病的噩梦。然而,万物相生相克,自然界中细菌自带“升级”功能,耐药性由此产生,发现新的抗生素和产生新的耐药性,被看作是“魔高一尺、道高一丈”的较量。尽管有越来越多的抗生素如雨后春笋般涌现出来,但大范围使用抗生素所导致的耐药性问题也逐渐凸显。耐药性的产生使正常剂量的抗生素不再发挥应有的杀菌作用,甚至使药物无效,从而给疾病的治疗增加难度,并容易使疾病加重。
基于抗生素产生耐药性可能的危害,寻找抗生素替代品成为一种新的挑战。抗菌肽是一类具有抗菌活性的碱性多肽物质,分子量在2000-7000之间,由10-60个氨基酸残基组成。这类活性多肽多数具有强碱性、热稳定性以及广谱抗菌等特点,尤其是其对某些耐药性病原菌的杀灭作用更引起了人们的重视。抗菌肽通过多种机制和不同途径发挥作用的能力,不仅增加了其抗菌活性,而且降低了发生耐药性的倾向。通过多种途径发挥作用可以很大程度上降低细菌同时获得多种突变的可能性,这使得抗菌肽在抗耐药性上具有很好的潜力。
磷脂酰肌醇3-激酶(PI3Ks)蛋白家族参与细胞存活、生长、代谢和血糖稳态等多种细胞功能的调控。吕峰在其博士论文中《p55PIK:慢性炎症分子干预新靶点》中阐述了p55PIK及其N末端24个氨基酸对LPS诱导下HaCaT细胞释放炎性因子的干预作用以及相应的作用机制。
专利CN113354714报道了以NMDA和p55PIK为双靶点的有效抑制炎症的结构,专利CN10106340报道了以NMDA和p55PIK为双靶点的有效抑制炎症的结构,融合多肽及其在肿瘤与细胞生长异常相关疾病治疗中的用途。上述专利相关的多肽簇序列主要为p55PIK蛋白相关序列中的活性基团偶联细胞穿透肽的情况。其中专利CN113354714中主要多肽序列为:YGRKKRRQRRR-MMTYSTELIFYIEMDP;专利CN10106340主要保护的多肽序列为:YGRKKRRQRRR-MDRDDADWREVMMPYSTELIFYIEM。
多肽是介于大分子蛋白质和小分子药物之间的具有调节细胞生物功能的化合物。由于其主要来源于天然多肽或者天然多肽类似物,通常情况下,其结构清楚、作用机制明确。多肽药物因其具有靶向性好、免疫原性低、组织渗透性好、易于合成和改造、安全性高、不易在组织中蓄积等优点,在抗肿瘤、抗菌、慢性代谢性疾病、心血管疾病、免疫疾病、镇痛等方面都表现出显著的疗效。
相比于多肽药物的优点,多肽药物的缺点也同样明显,比如在体内容易降解,剂型通常只能选择注射剂,透皮困难,很难外用。这些多肽药物的缺点大大限制了多肽药物本身的应用。
对于抗菌肽来说,除了本身的碱性特性,多肽序列本身的立体结构对于抗菌效果也有非常大的影响。比如α-螺旋和β-折叠结构,另外,多肽序列本身结构中的亲疏水性也将明显影响抗菌肽相应的抗菌活性。
发明内容
本发明的目的是基于多肽序列本身的立体结构和氨基酸亲疏水性,同时考虑多肽本身的作用途径和输送机制,开发一款新型的抗菌肽。
本发明的抗菌肽可以应用于各类感染性疾病及普通感染,作为抗生物的替代药物和改善药物。
为此,本发明提供的第一个技术方案是这样的:
一种抗菌肽,由细胞穿透肽X1与炎症抑制肽X2通过偶联获得;
所述的细胞穿透肽X1的氨基酸序列为SEQ ID No.1-SEQ ID No.8中的任意一种;
所述的炎症抑制肽X2的氨基酸序列为SEQ ID No.9-SEQ ID No.10中的任意一种。
进一步的,上述的抗菌肽,所述的抗菌肽氨基酸序列为SEQ ID No.11-SEQ IDNo.26中的任意一种。
进一步的,上述的抗菌肽,将氨基酸序列为SEQ ID No.11-SEQ ID No.26中的任意一条多肽的C-末端的第一个氨基酸残基偶联到固相载体上,然后依次按照SEQ ID No.11-SEQ ID No.26中这条多肽的氨基酸序列,把相应的氨基酸偶联到固相树脂上,偶联完成得到相应的肽树脂。
进一步的,上述的抗菌肽,当多肽的侧链为Lys、Trp残基用Boc保护;侧链为Ser、Thr、Tyr为残基时用tBu保护,侧链为Glu、Asp残基时用OtBu保护;侧链为Gln残基时,用Trt保护;侧链Arg和D-Arg残基时,用Pbf保护。
进一步的,上述的抗菌肽,细胞穿透肽X1与炎症抑制肽X2具体偶联的方法为:细胞穿透肽X1的C-末端氨基酸的羧基与炎症抑制肽N-末端氨基酸的氨基通过酰胺键进行偶联。
进一步的,上述的抗菌肽,采用Fmoc固相多肽合成技术完成氨基酸的偶联,然后从固相载体上把肽切割下来,最后肽树脂采用高效液相色谱进行纯化,得到高纯度的抗菌肽分子。
本发明提供的第二个技术方案是上述的抗菌肽作为制备治疗广谱抗炎药物的应用。
所述的炎症包括:结膜炎、角膜炎、巩膜炎、虹膜炎、睑腺炎、睑缘炎、睑皮炎、干眼症、中耳炎、化脓性中耳炎、外耳道炎、鼻炎、过敏性鼻炎、皮炎、溃疡糜烂、烧烫伤、红斑狼疮的其中之一。
一种广谱抗炎药物,包括权利要求1所述的抗菌肽以及常规辅料。
本发明提供的第三个技术方案是上述的一种广谱抗炎药物,所述的药物剂型为注射剂、片剂、胶囊、颗粒剂、口服液、软膏剂、乳膏剂、栓剂、凝胶剂、喷雾剂、滴眼剂、滴耳液、滴鼻剂、贴剂、洗剂中的一种。
本发明的有益效果为:
1、本发明的提供的抗菌肽,相比于炎症常规治疗中的抗生物,具有药效高、副作用小、产生耐药可能性低的有点。
2、本发明的提供的抗菌肽,基于药物的二级结构分析和分子设计,在亲水性较强的细胞穿膜肽中,基于d-螺旋形成的空间位点,加入相应的疏水性案件思源,具有更好的体内抗细菌感染治疗效果和更低的诱导细菌耐药性产生的倾向。
3、本发明的提供的抗菌肽,基于药物的作用机制和递送途径分析,选择对应的细胞穿透肽,可以达到最终外用的效果。
附图说明
图1为抗菌肽-26粗品的HPLC分析图
图2为抗菌肽-26纯品的HPLC分析图
具体实施方式
为了更清楚的理解本发明,现参照下列实施例进一步描述本发明。实施例仅用于解释而不以任何方式限制本发明。实施例中,各原始试剂材料均可商购获得,未注明具体条件的实验方法为所属领域熟知的常规方法和常规条件,或按照仪器制造商所建议的条件。
实施例1:多肽序列的合成
本实例提供的抗菌肽,由细胞穿透肽X1与炎症抑制肽X2通过偶联获得;
所述的细胞穿透肽X1的氨基酸序列为SEQ ID No.1-SEQ ID No.8中的任意一种,具体见表1;
所述的炎症抑制肽X2的氨基酸序列为SEQ ID No.9-SEQ ID No.10中的任意一种,具体见表2;
上述的抗菌肽,细胞穿透肽X1与炎症抑制肽X2具体偶联的方法为:
细胞穿透肽X1的C-末端氨基酸的羧基与炎症抑制肽N-末端氨基酸的氨基通过酰胺键进行偶联,得到氨基酸序列为SEQ ID No.11-SEQ ID No.26的多肽。
表1
表2
使用Fmoc固相多肽合成技术,首先将SEQ序列11-26中的任意一条多肽的C-末端的第一个氨基酸残基偶联到固相载体上,然后依次按照SEQ序列11-26中的任意一条多肽的序列,把相应的氨基酸偶联到固相树脂上。比如SEQ序列11:首先把Fmoc-Pro-OH偶联到固相载体上,然后依次偶联Fmoc-Asp(OtBu)-OH、Fmoc-Met-OH、Fmoc-Glu(OtBu)-OH、Fmoc-Ile-OH、Fmoc-Tyr(tBu)-OH、Fmoc-Phe-OH、Fmoc-Ile-OH、Fmoc-Leu-OH、Fmoc-Glu(OtBu)-OH、Fmoc-Thr(tBu)-OH、Fmoc-Ser(tBu)-OH、Fmoc-Tyr(tBu)-OH、Fmoc-Pro-OH、Fmoc-Met-OH、Fmoc-Met-OH、Fmoc-Arg(Pbf)-OH、Fmoc-Arg(Pbf)-OH、Fmoc-Trp(Boc)-OH、Fmoc-Arg(Pbf)-OH、Fmoc-Arg(Pbf)-OH、Fmoc-Trp(Boc)-OH、Fmoc-Trp(Boc)-OH、Fmoc-Arg(Pbf)-OH、Fmoc-Arg(Pbf)-OH。其它多肽序列采用与SEQ序列11相同的方法进行偶联。其中,Lys、Trp残基侧链用Boc保护,Ser、Thr、Tyr侧链用tBu保护,Glu、Asp侧链用OtBu保护,Gln侧链用Trt保护,Arg和D-Arg侧链用Pbf保护。偶联完成得到相应的肽树脂,具体肽序见表3。
表3
实施例2:肽树脂的裂解
将实施例1得到的肽树脂,采用裂解液(TFA:TIS:EDT:PhOH:H2O=90:3:3:2:2,体积比)进行裂解,室温反应2.5小时,滤掉树脂,树脂用50mlTFA洗涤,合并滤液,加入到无水乙醚中析出白色固体,离心,无水乙醚洗涤固体,真空干燥后,得到对应的粗肽。其中SEQ序列26的粗肽HPLC分析色谱图见图1。
实施例3:粗肽的纯化
用多肽纯化中通用的HPLC纯化方法,对实施例2中得到的上述进行纯化,得到纯度大于98%精肽。其中SEQ序列26的粗肽HPLC分析色谱图见图2。
纯化方法
1.样品预处理:称取粗品适量,加至烧杯中,加入含有3-7%乙腈的水溶液,搅拌溶清后过滤。制成浓度约为5-10mg/mL粗品溶液,待用。
2.一步纯化:将粗品溶液进行一步纯化,色谱条件:制备色谱柱:C18反相硅胶填料,色谱柱规格为50*250mm,流动相A:0.1%-0.5%TFA/水溶液,流动相B:0.1%-0.5%TFA/乙腈,检测波长:230nm,流速:50mL/min,上样量:0.5g-1g/次,洗脱梯度:0-60min B%为5%-35%;60-100min B%为35%-70%。收集纯度大于90%的馏分样品。
3.二步纯化:将一步纯化样品溶液进行二步纯化,色谱条件:制备色谱柱:C18反相硅胶填料,色谱柱规格为50*250mm,流动相A:0.1%-0.5%醋酸/水,流动相B:0.1%-0.5%醋酸/乙腈,检测波长:230nm,流速:50mL/min,上样量:0.5g-1g/次,洗脱梯度:0-60min B%为5%-25%;60-100min B%为25%-70%。收集纯度大于98%的馏分样品;
4.浓缩:将转盐液转移至旋蒸瓶中进行浓缩,浓缩温度为33~35℃,真空度P≤0.085mbar,去除乙腈和大部分水,浓缩时间不超过3h。
5.冻干:将浓缩样品溶液进行冻干,得到纯度大于98%的精肽。
具体纯化后的数据见下表4:
表4
实施例4:抗菌肽螺旋结构的测定
利用圆二色谱(CD)仪,在室温下常规条件(50mM KH2PO4/K2HPO4/100nM KCl,pH=7.0)和含有α-螺旋诱导剂三氟乙醇的溶液(50mM KH2PO4/K2HPO4/100nM KCl,pH=7.0缓冲溶液/50%的三氟乙醇)中,分别测定抗菌肽的平均残基摩尔椭圆率。
检测结果见下表5:
表5
SEQ ID序列号 | 温和条件螺旋率(%) | 50%三氟乙醇螺旋率(%) |
11 | 21.6 | 93.4 |
12 | 18.7 | 78.5 |
13 | 18.9 | 80.4 |
14 | 17.4 | 72.3 |
15 | 17.6 | 76.5 |
16 | 18.3 | 82.6 |
17 | 19.2 | 88.9 |
18 | 18.7 | 78.4 |
19 | 23.5 | 91.6 |
20 | 18.5 | 77.4 |
21 | 18.7 | 79.2 |
22 | 17.2 | 70.1 |
23 | 17.4 | 74.3 |
24 | 18.2 | 80.6 |
25 | 19.0 | 88.1 |
26 | 18.6 | 79.1 |
从表中结果可以看出,上述抗菌肽的α-螺旋处于较高的比率,这将有利于这些抗菌多肽的抗菌活性。
实施例6:抗菌肽对正常细胞的毒性
MTT法检测细胞的存活率。取两种成纤维细胞Fibrocyte-1和Fibrocyte-2,以每孔104个细胞接种于96孔的培养板,贴壁后分别予以0(对照组)、30、100μM的抗菌肽1-16。处理24h后,弃去培养液,每孔加入100μL的0.5μM的MTT培养液,并设置DMSO为调零孔。37℃避光孵育6小时,弃液后每孔加入100μL的DMSO,室温震荡5分钟。用酶联免疫检测仪测定570nm的吸光度值A570。细胞存活率(%)=处理组A570/对照组A570×100%。具体的结果见下表6:
表6
抗菌肽(SEQ ID序列号) | 浓度30μM的存活率(%) | 浓度100μM的存活率(%) |
11 | 99.96 | 99.83 |
12 | 99.85 | 99.69 |
13 | 99.90 | 99.73 |
14 | 99.56 | 99.51 |
15 | 99.72 | 99.68 |
16 | 99.82 | 99.78 |
17 | 99.59 | 99.38 |
18 | 99.54 | 99.42 |
19 | 99.91 | 99.87 |
20 | 99.31 | 99.20 |
21 | 99.46 | 99.39 |
22 | 99.57 | 99.52 |
23 | 99.86 | 99.78 |
24 | 99.05 | 98.93 |
25 | 99.74 | 99.60 |
26 | 99.33 | 99.29 |
从上述检测的结果可以看出,上述抗菌肽对正常细胞的人成纤维细胞基本没有太大的毒性影响,特别在低浓度(30μM)的条件下。这说明,抗菌肽对健康细胞无明显毒性。当上述抗菌肽被用作哺乳动物、尤其是人的治疗药物时,事实上基本不会发生太大的副作用。
实施例7:抗菌肽对皮肤抗感染实验
实验菌株:表皮葡萄球菌和金黄色葡萄球菌
实验方案:
动物模型:ICR小鼠:20g±3g,雌性,分为38组(每种菌液感染为19组),每组5只,分别为感染对照组、百多邦软膏对照组、16种1%抗菌肽喷剂对照组、空白喷剂对照组。其中1%抗菌肽喷剂和空白喷剂采用领域内公开方法进行正常制备。普通动物房饲养,自由摄水和进食。
菌液制备:取表皮葡萄球菌和金黄色葡萄球菌的菌株,分别接种于MHB培养基中,过夜培养,然后将培养后的菌液稀释至5×106CFU/ml,备用。
皮肤造模:将小鼠背部用脱毛膏脱毛,待毛发脱除干净后,用砂纸打磨至渗血,皮下注射相应的菌液,0.05ml。
给药:除感染对照组外,其余均涂抹对应的外用乳膏,剂量为0.1ml,早晚各一次,连续7天一个疗程。
检测:7天之后,无菌条件下取样本各脏器、血液及感染部分皮肤样本,检测活菌数量并统计。
抗菌肽喷剂对表皮葡萄球菌皮肤感染影响,相应的结果见下表7:
表7
组别 | 血液 | 皮肤 | 肝脏 | 脾脏 |
感染对照 | 152 | 12158 | 96 | 41 |
百多邦对照 | 32 | 397 | 21 | 12 |
抗菌肽-1 | 20 | 189 | 15 | 9 |
抗菌肽-2 | 13 | 102 | 6 | 5 |
抗菌肽-3 | 13 | 106 | 7 | 5 |
抗菌肽-4 | 23 | 236 | 11 | 9 |
抗菌肽-5 | 25 | 287 | 14 | 9 |
抗菌肽-6 | 29 | 301 | 15 | 10 |
抗菌肽-7 | 30 | 325 | 20 | 10 |
抗菌肽-8 | 14 | 114 | 8 | 5 |
抗菌肽-9 | 18 | 168 | 13 | 8 |
抗菌肽-10 | 12 | 82 | 5 | 4 |
抗菌肽-11 | 12 | 78 | 5 | 4 |
抗菌肽-12 | 19 | 208 | 9 | 7 |
抗菌肽-13 | 22 | 243 | 12 | 9 |
抗菌肽-14 | 27 | 269 | 12 | 9 |
抗菌肽-15 | 29 | 290 | 17 | 10 |
抗菌肽-16 | 11 | 73 | 6 | 5 |
空白对照 | 116 | 10302 | 61 | 32 |
抗菌肽喷剂对金黄色葡萄球菌皮肤感染影响,相应的结果见下表8:
表8
氨基酸序列为SEQ ID No.11-SEQ ID No.26的抗菌肽,依次记为抗菌肽-1-抗菌肽-16。
上述结果显示,抗菌肽1-16均有良好的对表皮葡萄球菌和金黄色葡萄球菌有一定的抑制作用。
实施例8:抗菌肽在中耳炎中的应用
实验方案:
采用蒸馏水、甘油配制1%抗菌肽的滴耳液。
取正常的雄性BALB/C小鼠95只,25g±2g,每只动物在实验前均通过耳窥镜检查无外耳道及中耳感染。留下5只作为正常对照组。另外90只通过分泌型中耳炎建模,得到分泌型中耳炎模型的小鼠,分为18组,每组5只。分别为感染对照组、左氧氟沙星滴耳液对照组、16种1%抗菌肽喷剂对照组,普通动物房饲养,自由摄水和进食。
给药:每次给药0.2ml,每天两次,早晚各一次,连续7天为一个疗程,连续两个疗程。其中,正常对照组和感染对照组分别滴加不含任何药物成分的滴耳液(蒸馏水和甘油)。
14天实验结束后,麻醉处死所有样本,取双侧耳泡,用质量分数为4%的多聚甲醛固定,再用质量分数为5%的硝酸水溶液脱钙,石蜡包埋切片,常规染色光镜下检测鼓室黏膜增生情况。用测微计在光镜下测量各组中耳黏膜厚度。
抗菌肽对中耳黏膜厚度影响的结果,相应的结果见下表9:
表9
组别 | 肿胀度(mg) |
正常对照 | 0.0815±0.01263 |
感染对照 | 0.8756±0.09702 |
左氧氟沙星 | 0.4260±0.04147 |
抗菌肽-1 | 0.3478±0.03892 |
抗菌肽-2 | 0.1809±0.02653 |
抗菌肽-3 | 0.1713±0.02599 |
抗菌肽-4 | 0.2963±0.05167 |
抗菌肽-5 | 0.3081±0.04469 |
抗菌肽-6 | 0.3894±0.07368 |
抗菌肽-7 | 0.4315±0.06708 |
抗菌肽-8 | 0.2147±0.03657 |
抗菌肽-9 | 0.3192±0.02674 |
抗菌肽-10 | 0.1788±0.03029 |
抗菌肽-11 | 0.1684±0.02791 |
抗菌肽-12 | 0.2876±0.06304 |
抗菌肽-13 | 0.2985±0.05713 |
抗菌肽-14 | 0.3609±0.0684 |
抗菌肽-15 | 0.4298±0.07359 |
抗菌肽-16 | 0.1942±0.03576 |
备注:氨基酸序列为SEQ ID No.11-SEQ ID No.26的抗菌肽,依次记为抗菌肽-1-抗菌肽-16。
从表中数据可以看出,小鼠感染中耳炎之后,中耳黏膜厚度明显增厚。而使用左氧氟沙星滴耳液之后,黏膜厚度降低,说明左氧氟沙星滴耳液对于炎症也有一定的效果。使用抗菌肽1-16之后,小鼠中耳黏膜厚度均有降低,说明上述抗菌肽对于中耳炎均有一定的疗效。从数据看,抗菌肽2、3、8、10、11、16的效果最好。
显然,上述实施例仅仅是为清楚地说明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其他不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
1.一种抗菌肽,其特征在于,由细胞穿透肽X1与炎症抑制肽X2通过偶联获得;
所述的细胞穿透肽X1的氨基酸序列为SEQ ID No.1-SEQ ID No.8中的任意一种;
所述的炎症抑制肽X2的氨基酸序列为SEQ ID No.9-SEQ ID No.10中的任意一种。
2.根据权利要求1所述的抗菌肽,其特征在于,所述的抗菌肽氨基酸序列为SEQ IDNo.11-SEQ ID No.26中的任意一种。
3.根据权利要求1所述的抗菌肽,其特征在于,将氨基酸序列为SEQ ID No.11-SEQ IDNo.26中的任意一条多肽的C-末端的第一个氨基酸残基偶联到固相载体上,然后依次按照SEQ ID No.11-SEQ ID No.26中这条多肽的氨基酸序列,把相应的氨基酸偶联到固相树脂上,偶联完成得到相应的肽树脂。
4.根据权利要求1所述的抗菌肽,其特征在于,当多肽的侧链为Lys、Trp残基用Boc保护;侧链为Ser、Thr、Tyr为残基时用tBu保护,侧链为Glu、Asp残基时用OtBu保护;侧链为Gln残基时,用Trt保护;侧链Arg和D-Arg残基时,用Pbf保护。
5.根据权利要求1所述的抗菌肽,其特征在于,细胞穿透肽X1与炎症抑制肽X2具体偶联的方法为:细胞穿透肽X1的C-末端氨基酸的羧基与炎症抑制肽N-末端氨基酸的氨基通过酰胺键进行偶联。
6.根据权利要求1所述的抗菌肽,其特征在于,所述的抗菌肽,采用Fmoc固相多肽合成技术完成氨基酸的偶联,然后从固相载体上把肽切割下来,最后采用高效液相色谱进行纯化,得到高纯度的抗菌肽分子。
7.权利要求1所述的抗菌肽作为制备治疗广谱抗炎药物的应用。
8.根据权利要求7所述的抗菌肽作为制备治疗广谱抗炎药物的应用,其特征在于,所述的炎症包括:结膜炎、角膜炎、巩膜炎、虹膜炎、睑腺炎、睑缘炎、睑皮炎、干眼症、中耳炎、化脓性中耳炎、外耳道炎、鼻炎、过敏性鼻炎、皮炎、溃疡糜烂、烧烫伤、红斑狼疮的其中之一。
9.一种广谱抗炎药物,其特征在于,包括权利要求1所述的抗菌肽以及常规辅料。
10.根据权利要求9所述的一种广谱抗炎药物,其特征在于,所述的药物剂型为注射剂、片剂、胶囊、颗粒剂、口服液、软膏剂、乳膏剂、栓剂、凝胶剂、喷雾剂、滴眼剂、滴耳液、滴鼻剂、贴剂、洗剂中的一种。
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