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论文范文：氨甲环酸柔性纳米脂质体凝胶的制作和体外释药分析第一章绪论皮肤色素沉着是临床上皮肤科常见的病症之一，它是由于皮肤受到紫外线照射、炎症刺激等外源性因素和自身疾病引起的内源性因素使大量黑色素非正常聚集于皮肤的不同部位，在皮肤表面呈现出局部颜色变黑，如黑斑息肉综合征、特发性多发性斑状色素沉着、黄褐斑、雀斑、色斑及老年斑等[1]。
皮肤色素沉着类疾病尽管没有疼痛、瘙痒等痛苦，但由于黑色素沉着导致的皮肤肤色不均，进而影响到人们的日常生活。
随着社会的发展，抗色素沉着类疾病引起了人们的关注，从而出现了各式各样祛斑产品和治疗方法[5]。
氨甲环酸(TranexamicAcid，TA)作为一种蛋白酶抑制剂，抑制黑斑部位表皮细胞的机能，改善黑斑部位活性化因子群的活跃状态[6]，抑制黑色素的生产而被应用于治疗色素沉着等病症。
目前临床上使用TA 治疗色素沉着疾病多是口服或静脉注射给药，常引起胃肠道刺激等不良反应[7_8]。
经查阅文献的得知：TA作为经皮给药制剂的主要剂型是膏剂，然而因皮肤角质层这一主要的物理屏障，疗效不显著。
近年来，在新技术和新设备不断发展的情况下，关于经皮给药系统在促进药物透皮吸收的方法方面取得了很大的进步[9]。
微乳[iG]、固体脂质纳米粒[11]、脂质体[12]等新型药物载体可与角皮肤质层具有很高的融合性，从而将药物传递到皮肤内部来克服皮肤角质层屏障的影响。
柔性纳米脂质体(Flexible nano-liposomes，FNL)是在脂质体的类脂材料中加入胆酸钠、脱氧胆酸钠等表面活性剂，使其除具有普通脂质体经皮给药系统的优点如生物利用度高、皮肤亲和力好和安全无毒外，还具有高度的变形性、适宜的亲水性和渗透性[13]。
因此能够高效地穿透比自身小数倍的皮肤孔道。
此外，柔性纳米脂质体的结构类似于生物膜结构，与皮肤角质层具有很高的融合性，可以使药物尽可能多地在皮肤的表皮和真皮层内形成一个药物e库，而发挥其缓释效果，使药物能够在局部病变部位持久地起治疗作用。
-实验研宪-0.05%环抱素A纳米粒滴眼液治疗干眼症的实验研究林琳曹俊昌杨政冯春燕【摘要】目的观察0.05%环抱素A纳米粒滴眼液对干眼症的治疗效果$方法将新西兰兔24只随机分为4组，空白组、阴性对照组、0.05%环抱素A滴眼液组、0.05%环抱素A纳米粒滴眼液组，每组6只$利用东萇M碱诱导干眼模型，造模成功后开始实验干预：阴性对照组不予处理(.05%环抱素A滴眼液组及0.05%环抱素A纳米粒滴眼液组分别给与相应滴眼液％次/天，共持续28天$在干预第1、2、3、4周分别进行Schirmer1(SIT)试验、泪膜破裂时间(BUT)&角膜荧光素染色(CFS)检测$并于干预结束后光镜下观察结膜组织的病理学改变。
结果与空白组相比，造模后各干预组泪液分泌量明显减少、泪膜破裂时间显著缩短(P V0.05)与阴性对照组相比，干预后同时段0.05%环抱素A滴眼液组及0.05%环抱素A纳米粒滴眼液组泪液分泌量增加、泪膜破裂时间延长，干预第1周改善效果最为明显，且0.05%环抱素A纳米粒滴眼液组效果更为显著(!"0.05)$造模后结膜上皮结构紊乱，杯状细胞反应性增多、胞浆丰富，固有层炎性细胞浸润增多$0.05%环抱素A滴眼液组及0.05%环抱素A纳米粒滴眼液组干预4周后，结膜上皮形态排列结构趋于规则，杯状细胞数量减少、胞浆丰富，固有层炎性细胞浸润减少，且0.05%环抱素A纳米粒滴眼液干预效果更为显著$结论0.05%环抱素A纳米粒滴眼液能够有效改善干眼症状，且效果优于传统的0.05%环抱素A滴眼液$【关键词】环抱素A；纳米粒滴眼液；干眼症DOI：10.3969/j.issn.1674-9006.2021.01.001中图分类号：R77The treatment of0.05%cyclosporine a nanoparticle eye drops on dry eye disease Lin Lin,Cao Junchang,Yang Zheng-,Feng Chunyan(The Second A f f iliated Hospital of Fujian University of TCM,Fuzhou,Fujian,350000)[Abstract#Objective To observe the therapeutic effect of0.05%cyclosporine A nanoparticle eyedrops on dry eye disease.Methods24New Zealand rabbits were randomly divided into4groups：blankgroup,negative control group,0.05%cyclosporin A eye drops group,and0.05%cyclosporin A nanoparti-cleeyedropsgroup%with6rabbitsineach.Thedryeyemodelwasinducedbyscopolamine%fo l owedbytheexperimental intervention started after successful modeling:the negative control group was not treated；the0.05%cyclosporin A eye drops group andJhe0.05%cyclosporin A nanopar icle eye drops group were given JhecorrespondingeyedropsJhree imesadayforaJoJalof28days.AndJhen%JheSchirmerIJesJ(SIT)%tear film break-up time(BUT),and corneal fluorescein staining(CFS)tests were performed at weeks1,2,3%Dnd4ofintervention.ThepDthologicDlchDngesofconjunctivDltissueswereDlsoobservedunderDlightmicroscope after the end of the intervention.Results Compared with the blank group,the tear secretion wassignificantly reduced,and the BUT was significantly shortened in each intervention group after modeling(P V0.05).Compared to the negative control group,the tear secretion increased and the BUT prolonged atJhesame ime inJerval inJhe0.05%cyclosporine A eye drops group and0.05%cyclosporine A nanopar icleeye drops group after intervention.Meanwhile,the improvement effect was most significant in the firstweek of intervention,and in the0.05%cyclosporine A nanoparticle eye drops group(P V0.05).Aftermodel establishment,the structure of conjunctival epithelium was disordered,coupling with increased goblet基金项目：福建省卫健委青年科研课题(2018-1-84)作者单位'50000,福建福州，福建中医药大学附属第二人民医院眼科通讯作者：冯春燕，E-mail：19563671@cell reactivity,abundant cytoplasm and increased inflammatory cell infiltration in the lamina propria.After4 weeks of intervention in the0.05%cyclosporine A eye drops group and0.05%cyclosporine A nanoparticle eye drops group,the morphological arrangement structure of the conjunctival epithelium tended to be regular,together with decreased number of goblet cells,abundant cytoplasm,decreased infiltration of inflammatory cells in the lamina propria,as well as more significant intervention effect of0.05%cyclosporine A nanoparticle eye drops.Conclusion The0.05%cyclosporin A nanoparticle eye drops can effectively improve thesymptomsofdryeyewithbe t ere f ectthanthatoftraditional0"05%cyclosporineAeyedrops"【Keywords】Cyclosporine A；Nanoparticle eye drops；Dry eye disease环抱素A（CsA）是一种强效的免疫抑制剂，因其作用效果显著、特异性较高而被广泛的应用于器官移植术后免疫排斥反应的防治。
环孢素A眼用乳剂凝胶的研究杜爽;孙春萌;沈雁;涂家生【期刊名称】《药学与临床研究》【年(卷),期】2011(19)3【摘要】目的:制备一种环孢素A眼用乳剂凝胶(CsAE-gel),并对其含量和体外释放度进行考察.方法:采用响应面Box-behnken设计对CsAE-gel中乳剂的处方及工艺进行优化,另外通过调节pH考察凝胶黏度对乳剂稳定性的影响,以建立最终处方.采用HPLC方法测定CsAE-gel中CsA含量,色谱柱为Waters XBridge C18(4.6 mm×150mm,5μm),流动相为乙腈-水-甲醇-磷酸(550∶400∶50∶0.5,v/v),检测波长210 nm,柱温70℃.并考察了凝胶黏度及灭菌对体外释放的影响.结果:CsA在浓度0.4～16μg·mL-1范围内呈良好的线性关系(r=1),日内和日间RSD分别为0.24%和0.41%,平均回收率为99.0%.灭菌及凝胶黏度对CsAE-gel体外释放均无显著影响.结论:CsAE-gel稳定性好,体外释放效果良好,流变学性质符合眼用制剂要求.%Objective: To prepare an ophthalmic emulsive gel of cyclosporine A (CsA E-gel), and investigate its content and in-vitro releaseactivity.Methods: The formulation and production of CsA E-gel was optimized using the Box-behnken surface response design, and the effect of the gel viscosity under different pH on the stability of emulsion was investigated.Based on the results, the optimal formulation was established.The content of CsA in CsA E-gel was determined by HPLC.The separation was carried out on a Waters XBridge C18 column (4.6 mm×150 mm, 5 μm), eluted with the mobile phase of acetonitrile-water-methanol-phosphoric acid (550∶ 400∶50∶0.5).The flow rate was 1.2 mL·min-1, the detection wavelengthwas 210 nm, and the column temperature was 70℃.In addition, the effects of the gel viscosity and sterilization on in-vitro release activity were also determined.Results: A good linear relationship was found over a concentration range of 0.4～16 μg·min-1, with a correlation coefficient of 1.The RSD values of interday and intra-day precision were 0.24％ and 0.41％ respectively.The average recovery of CsA was 99.0％.There was no significant effect of the gel viscosity and sterilization on in-vitro release activity.Conclusion:The CsA E-gel has a good stability and in-vitro release activity, and its rheological property meets the requirements of ophthalmic preparatior.【总页数】5页(P215-219)【作者】杜爽;孙春萌;沈雁;涂家生【作者单位】中国药科大学药剂教研室,南京,210009;中国药科大学药剂教研室,南京,210009;中国药科大学药剂教研室,南京,210009;中国药科大学药剂教研室,南京,210009【正文语种】中文【中图分类】R988.1;R944.9【相关文献】1.环孢素眼植入凝胶膜的制备及其体外释放研究 [J], 陈建英;凌沛学;贺艳丽;刘杰;汪敏2.环孢素眼植入凝胶膜的制备及其体外释放研究 [J], 陈建英;凌沛学;贺艳丽;刘杰;汪敏3.LC-MS/MS法测定人全血中环孢素A浓度及环孢素眼用乳剂健康人体药代动力学研究 [J], 王淑民;李鹏飞;赵秀丽;马萍;刘丽宏4.环孢素眼用乳剂的制备及质量控制 [J], 王延东;陈茂玲;叶成添;唐细兰5.加拿大批准环孢素0.05%眼用乳剂Restasis治疗干眼病 [J], 马培奇因版权原因，仅展示原文概要，查看原文内容请购买。
f or m a hu ei ch i ngensi s H si ao[J].Y aku gaku Z asshi ,1971,91(5):593-596.[2]刘庆丰，孙启祥，胡雅儿，等.地黄中的梓醇对β肾上腺素受体c A M P 系统的调整作用[J ].放射免疫学杂志，2004，17（5）:358-360.[3]R e ci o MC ,G i ne r R M ,M anez S,et al.S tr u ct u r al con si d er -at i ons on t he i r i doids as anti -i nf l am m at or y agent s[J].Pl ant a M ed,1994,60(3):232-234.[4]M e hr ot r a R ,R aw at S,K ul shr e sht ha D K ,et al.In v i tr o f f f B []I M R ,,333[5]温学森，杨世林，马小军，等.地黄在加工炮制过程中H PLC 谱图的变化[J].中草药，2004，35（2）:153-156.[6]徐智，吴国明，钱桂生，等.大鼠衰老模型的初步建立[J].第三军医大学学报，2003，25(4):312-315.[7]赵宇，温学森，崔晶，等.鲜地黄中α-半乳糖苷酶和β-葡萄糖苷酶的提取与初步纯化[J].中药材，2006，29（2）:137-139.[8]肖敏，刘树锋，朱崇日，等.短双歧杆菌α-D -半乳糖苷酶的纯化及性质[J].中华微生物学和免疫学杂志，2001，（3）33收稿日期：2008-07-31作者简介：陈建英（1970-），女，高级工程师E-m a i l :dudum a m a 2001@s i na.c om*通讯作者：贺艳丽，女，研究员E-m a i l :he yanl i 0622@si na.c om环孢素眼植入凝胶膜的制备及其体外释放研究陈建英，凌沛学，贺艳丽*，刘杰，汪敏（山东省生物药物研究院，山东济南250108）摘要：目的以交联透明质酸为载体制备环孢素眼植入凝胶膜，观察其体外药物释放特性。
环孢素眼用乳剂的制备及质量控制作者：王延东陈茂玲叶成添唐细兰来源：《中国实用医药》2010年第12期【摘要】目的研制低浓度的环孢素眼用乳剂,并建立该制剂的质量控制方法。
方法采用羟丙甲纤维素为增稠剂,按处方制备低浓度的环孢素眼用乳剂,用高效液相色谱法测定环孢素的含量,观察家兔眼部刺激性,并对制剂的稳定性进行考察。
结果环孢素在5~60 mg/L浓度范围内线性关系良好(r=0.9999),平均回收率为 100.39%,相对标准偏差(RSD)为 1.15%。
滴眼后无刺激性,而且稳定性较好。
结论该制剂制备工艺简单,含量测定方法简便、准确,质量稳定,对眼部无刺激性,是一种较理想的眼用制剂,可用于干眼症及其他眼部免疫性疾病的治疗。
【关键词】环孢素;眼用乳剂;制备;质量控制Preparation and quality control of ciclosporin ophthalmic emulsionWANG Yan-dong,CHEN Mao-ling,YE Cheng-tian,et al.Zhongshan Ophthalmic Center,Sun Yat-senUniversity,Guangdong,Guangzhou 510060,China【Abstract】 Objective To prepare low concentration ciclosporin ophthalmic emulsion and establish its quality control methods.Methods Low concentration ciclosporin ophthalmic emulsion was prepared by means of the formula.Hypromellose was used as thickening agent and the content of ciclosporin was determined by HPLC.Stimulus of ciclosporin on rabbits’ eye and the stability of low concentration ciclosporin ophthalmic emulsion were observed.Results The calibration curve of ciclosporin was linear within the concentration range of 5~60 mg/L,r=0.9999.The average recovery of ciclosporin was 100.39%,(RSD=1.15%).Ciclosporin had no stimulus on rabbits’ eye and its stability was very good.Conclusion The preparation is simple,its content determination is convenient and accurate,quality is stable,and it has stimulus on eyes.It is an ideal ophthalmic preparation and can be used to cure dry eyes and other ophthalmic immune diseases.【Key words】Ciclosporin;Ophthalmic emulsion;Preparation;Quality control干眼症是最常见的眼表疾病之一,严重干眼症患者可引起视力明显下降而影响工作和生活,甚至导致失明,长期以来无特效疗法[1,2]。
(19)中华人民共和国国家知识产权局(12)发明专利申请(10)申请公布号 (43)申请公布日 (21)申请号 202011164106.7(22)申请日 2020.10.27(71)申请人 成都市妇女儿童中心医院地址 610000 四川省成都市青羊区日月大道一段1617号(72)发明人 许飞 (74)专利代理机构 成都行之专利代理事务所(普通合伙) 51220代理人 胡晓丽(51)Int.Cl.A61K 38/13(2006.01)A61K 9/06(2006.01)A61K 47/22(2006.01)A61P 9/10(2006.01)A61P 9/00(2006.01)A61K 49/00(2006.01)(54)发明名称水凝胶搭载环孢素A在制备治疗心肌缺血再灌注损伤的药物中的应用(57)摘要本发明公开了水凝胶搭载环孢素A在制备治疗心肌缺血再灌注损伤的药物中的应用，解决了现有技术存在的环孢素A直接给药毒性过大问题，通过水凝胶搭载环孢素A的给药方式，不仅可以局部增加CsA药效而减少全身毒性作用，还可以通过具有局部电传导和粘合作用的水凝胶A心脏补片改善心梗后的心肌损伤。
权利要求书1页 说明书6页 附图2页CN 112168952 A 2021.01.05C N 112168952A1.一种治疗心肌缺血再灌注损伤的药物，其特征在于，包括：水凝胶和环孢素A。
2.水凝胶搭载环孢素A在制备治疗心肌缺血再灌注损伤的药物中的应用。
3.水凝胶搭载环孢素A在构建大鼠心肌缺血再灌注损伤模型中的应用。
4.根据权利要求3所述的水凝胶搭载环孢素A在构建大鼠心肌缺血再灌注损伤模型中的应用，所述大鼠心肌缺血再灌注损伤模型的构建方法包括以下步骤：(1)将SD大鼠分为5组，分别为假手术组、模型组、CsA腹腔注射组、水凝胶A组、含CsA水凝胶A组，除假手术组外均进行LAD结扎；(2)分别在再灌注3h、24h、48h和7d，取大鼠静脉血，检测血液中炎症因子的表达、线粒体DNA含量、促凋亡因子细胞色素C表达变化；(3)采用小动物心脏彩超检测心脏收缩功能，包括左心室射血分数、左心室短轴缩短率；(4)取大鼠心脏，采用TTC染色法检测大鼠的心梗面积，同时取部分心肌组织检测心肌细胞凋亡指标的表达变化、心肌细胞mPTP的开放程度。
环孢素A微乳巴布膏眼贴的制备及体外透皮实验陈敏;许丽疆;翁景宁;上官晓辉;严俊;黄金棋;陈丹娜【摘要】背景:免疫性眼病如甲亢性突眼、葡萄膜炎等疾病严重危害患者的眼健康,是眼科的常见病和疑难病,目前最常见的治疗方法为口服激素和免疫抑制剂,疗效不佳、反复发作、预后差同时全身不良反应很大.此类疾病多有淋巴细胞直接或间接参与.尝试把免疫抑制剂制作成巴布膏眼贴,通过局部外用使药物进入体内,利用环孢素A微乳的淋巴靶向性能,使环孢素A作用在睑周淋巴结,从而达到治疗或控制睑周淋巴结参与反应的免疫性眼病.这种方法为局部外用,不用全身用药,针对性强,药物剂量小,如果治疗效果好,可以有效治疗免疫性眼病并规避原有药物全身应用及长期应用的不良反应.目的:制备环孢素A微乳巴布膏眼贴,研究环孢素A微乳巴布膏眼贴体外透皮吸收特性.方法:将环孢素A微乳与聚丙烯酸钠、聚乙烯醇、聚乙烯吡络烷酮、明胶、桃胶、羧甲基纤维素钠、羟丙基纤维素等的水溶性高分子材料混合物以1 mg:1 mL的比例充分混匀,涂布于无纺布上制备成巴布膏.Franz扩散池法测定该巴布膏在ICR小鼠腹部皮肤的通透性.高效液相色谱分析法检测环孢素A浓度,并进行皮肤刺激性和过敏性实验.结果与结论:实验成功制备了粘性适宜、透气透水性能良好、敷贴舒适、无皮肤刺激性和过敏反应的环孢素A微乳巴布膏,环孢素A含量为10 mg/片,质量浓度为1 g/L.环孢素A微乳透皮的浓度随着时间的增加而增加,具有较好的透皮效果.证实将环孢素A微乳制备成巴布膏眼贴是可行的.其在透皮性能、黏附能力、皮肤舒适方面表现良好.%BACKGROUND: Immune eye diseases such as hyperthyroidism exophthalmos and uveitis seriously endanger the eye health of patients, which are common and difficult eye diseases. Current treatments for these diseases include oral administration of hormones and immunosuppressive agents, with poor efficacy, recurrentattacks and poor prognosis. Meanwhile, these treatments can induce systemic adverse reactions. Lymphocytes are directly or indirectly involved in these diseases. Therefore, we try to make papua eye patch carrying immunosuppressant, and deliver the drug through the topical use. Cyclosporin A microemulsion targeting lymphocytes can treat or control palpebral lymph nodes involved in the immune eye diseases. It is a topical method rather than the systemic medication, which is targeted and has small doses of drugs. If possible, this treatment can effectively treat immune eye diseases and avoid systemic drug adverse reactions and long-term adverse reactions induced by original drugs. OBJECTIVE: To study the preparation of cyclosporin A microemulsion papua cream eye patch, and its transdermal absorption characteristics in vitro. METHODS: Cyclosporine A microemulsion was fully mixed with water-soluble polymer materials at a ratio of 1 mg:1 mL, including sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, gelatin, peach gum, sodium carboxymethylcellulose, hydroxypropylcellulose, and then coated onto the non-woven fabric to prepare Babu cream. Permeability of the Babu cream on the abdominal skin of ICR mice was determined by Franz diffusion cell method. High-performance liquid chromatography was used to detect the concentration of cyclosporine A, and skin irritation and anaphylaxis were also measured. RESULTS AND CONCLUSION: Cyclosporin A microemulsion papua cream eye patch was successfully prepared with appropriate viscosity, good permeability, good permeability, comfortable application, no skin irritation and allergic reaction. The content of cyclosporine A was 10 mg/tablet, andthe concentration was 1 g/L. The concentration of cyclosporine A microemulsion increased with the increase of time, and it had good transdermal effect. This study proved that it is feasible to prepare cyclosporine A microemulsion into papua patch. It has good performance in skin permeability, adhesion and skin comfort.【期刊名称】《中国组织工程研究》【年(卷),期】2018(022)010【总页数】6页(P1553-1558)【关键词】环孢素A微乳;巴布膏;眼贴;工艺研究;体外透皮;免疫性眼病;甲状腺相关眼病;局部给药;生物材料【作者】陈敏;许丽疆;翁景宁;上官晓辉;严俊;黄金棋;陈丹娜【作者单位】莆田学院附属医院眼科,福建省莆田市 351100;莆田学院附属医院眼科,福建省莆田市 351100;福建医科大学附属协和医院眼科,福建省福州市 350000;福建医科大学附属龙岩市第一医院血液风湿科,福建省龙岩市 364000;莆田学院附属医院血液风湿科,福建省莆田市 351100;莆田学院附属医院血液内科,福建省莆田市 351100;厦门大学药学院转化医学中心,福建省厦门市 361102;莆田学院细胞与基因工程研究所,福建省莆田市351100;莆田学院附属医院眼科,福建省莆田市351100【正文语种】中文【中图分类】R3180 引言 Introduction眼部发生一系列的免疫病理变化，引起眼部各种免疫性疾病的发生，统称为免疫性眼病[1]。
