【作者】 王嫄；

【导师】 朱豫；

【作者基本信息】 郑州大学 ， 眼科学， 2011， 硕士

【摘要】 目的眼膏在眼科疾病治疗中的应用十分广泛,能在结膜囊内维持长时间的有效药物浓度。其主要是由药物成分和赋形剂制作而成,赋形剂的选择不同,可能导致眼膏对眼表或药物作用部位的不良反应存在差异。近些年,诸多文献研究指出将眼膏应用于泪道探通术后,能起到支撑泪道和防治泪道再粘连的作用,但也有报道称眼膏通过手术或创伤之假道进入眼结膜下、眶内组织及眼睑和泪囊周围组织时,将引起严重的炎症反应,且治疗比较棘手。本实验目的：观察不同基质的外用眼膏进入结膜下组织后引起的不良反应情况,筛选出基质可降解吸收、不良反应较少的眼膏,为临床工作中正确选用眼膏提供一定的实验依据,并起到一定的指导作用。材料与方法1.动物与分组2-4周龄的健康清洁级豚鼠72只,体重120-150 g,雌雄兼用,无眼部疾患及头面部异常。随机数字表法分为A、B、C三组,每组24只。2.动物模型制作盐酸奥布卡因滴眼液行豚鼠眼表面麻醉,在显微镜下使用1 ml注射器和7号(22 G)注射针头,A组右眼上方球结膜下注射以凡士林、羊毛脂和液状石蜡为基质的红霉素眼膏0.2 ml,B组右眼上方球结膜下注射以玻璃酸钠和卡波姆为基质的氧氟沙星眼膏0.2ml,C组作为对照组,右眼上方球结膜下注射羟丙基甲基纤维素0.2 ml。3.观察项目和时间点分别于结膜下注射三种药物后立即观察药物在结膜下聚集情况；注射后1d、3d、7d、14d、21d、28d观察结膜肿胀程度,以0、+、++、+++表示：0为无明显肿胀,+为结膜水肿扁平隆起、无皱褶形成,++为结膜隆起、睑裂区可见,+++为结膜泡状隆起、突出睑裂、部分遮盖角膜上缘；注射后上述六个时间点观察药物扩散与降解吸收情况；以及上述六个时间点的结膜组织病理学变化。4.统计学分析采用SPSS17.0统计软件进行统计学分析。三组间结膜肿胀程度的有序变量资料采用秩和检验,检验标准a=0.05,P<0.05为差异有统计学意义。结果1.三种药物注射到局部的情况注射后立即观察,A组药物在结膜下呈黄白色油质状；B组药物呈淡白色半透明状；C组药物在结膜下呈液状透明。2.三种药物注射后结膜肿胀程度A组：结膜肿胀以+++为主,14d发生明显变化,0只眼为+++,21 d、28 d结膜仍见肿胀,未见明显消退。B组：结膜肿胀以++为主,14 d结膜肿胀程度明显减轻,范围明显缩小,28 d结膜肿胀完全消退。C组：结膜肿胀以+为主,7d结膜肿胀逐渐消退,14d结膜肿胀已完全消退。三组间结膜肿胀程度在1d、3d、7d比较差异有统计学意义(P<0.05)。3.药物扩散与降解吸收情况A组：注射眼膏后3d开始,眼膏逐渐向四周球结膜下扩散,但未见明显降解吸收。B组：从3d开始,见眼膏向下方球结膜下扩散,并随着扩散逐渐被降解吸收,28 d眼膏已被完全吸收。C组药物各个时间点均未见扩散,于注射后1d开始逐渐被降解吸收,14d时已被完全降解吸收。4.组织病理学观察A组：见以中性粒细胞为主的炎症细胞浸润结膜组织,包括淋巴细胞,大量成纤维细胞及纤维组织增生；21d、28d纤维组织增生机化,炎症细胞基本消失。B组：见以中性粒细胞为主的炎症细胞浸润结膜组织,周围血管扩张充血,仅少量纤维组织增生；28 d结膜结构基本恢复正常。C组：仅有少量炎症细胞浸润结膜组织,7d炎症细胞消失,未见纤维组织增生,14d结膜结构恢复正常。结论以凡士林、羊毛脂和液状石蜡为基质的眼膏进入组织中将引起严重的炎症反应,建议不要用于有创口的组织表面。以玻璃酸钠和卡波姆为基质的眼膏进入结膜下组织后仅引起轻度的组织炎症反应,认为用于泪道探通术后可起到支撑管腔和防止组织粘连的作用。羟丙基甲基纤维素不引起明显的炎症反应,但由于其黏度较低,不用于泪道探通术后注入泪道内。更多还原

【Abstract】 PurposeOculentum is widely used in the treatment of eye disease, and the medicine density can be kept effectively in the conjunctiva sac for a long time. It is mainly manufactured by pharmaceutical ingredients and excipients, if the excipients are different, the adverse reactions caused by eye oculentum to the surface of ocular or the position affected by drugs are different. In recent years, researchs in many documents point out that the oculentum can sustain the lacrimal duct and avoid the lacrimal duct being conglutinated again if it is applied to lacrimal surgery, but the oculentum can also cause severe inflammation and it is hard to be treated if it goes into the subconjunctival tissue, orbital tissues, the tissue surrounding lacrimal sac and the eyelids through the false passage caused by surgery or trauma.The purpose of the experiment is to observe the adverse reactions caused by the different substrate oculentum when they are going into the subconjunctival tissue. The eye oculentums, which have little side effects and can be degraded and absorbed, are selected. This can provide experimental evidence and plays a role of instruction for the selection of eye oculentums in the clinical work.Materials and methods 1. Animals and Grouping72 guinea pigs, which are healthy and in clean level,2 to 4 weeks old, weighing 120～150 g, were selected. Male and female was open, and excluded a variety of eye diseases. They were randomly divided into three groups of A, B, C, and 24 in every group.2. Animal model productionAfter the ocular surface anesthesia by the eye drops of hydrochloric acid Ao Buka, the erythromycin eye oculentum, which takes vasline, lanolin and liquid paraffin as substrate, was injected into upper subconjunctival tissue of the right eye of guinea pigs in 0.2ml using 1 ml syringes and 7 (22 G) needle under the microscope in group A. The ofloxacin eye oculentum, which takes the sodium hyaluronate and carbomer as substrate, was injected into upper subconjunctival tissue of the right eye of guinea pigs in 0.2ml in group B. The hydroxypropyl methylcellulose was taken as a contrast and was injected into upper subconjunctival tissue of the right eye of guinea pigs in 0.2ml in group C.3. Project and time pointsTo observe the accumulative situations after the three drugs were injected into the subconjunctival tissue immediately;the swelling of the conjunctiva on the day of 1d,3d,7d,14 d,21 d,28 d were observed, just as 0,+,++,+++:0 shows it is have no obvious swelling,+shows the conjunctival edema is flat elevation and have no wrinkle,++shows the conjunctiva is upheaved and the area of palpebral fissure is visible,+++shows the conjunctiva is upheaved like the bubble and escaped from palpebral fissure, and the conjunctiva which is severe swelling covered the upper edge of the cornea partially; the diffusion, degradation and absorption of drugs at the above of six time were observed, the histopathological changes of the conjunctiva at the six time above were observed.4. Statistical analysisSPSS17.0 statistical software was used for statistical analysis. The method of Rank sum test was used to analyze the difference rates of the conjunctival swelling among the three groups. Inspection standard was 0.05, and P<0.05, so it had statistical significance. Results1. The situation of the three drugs injected into the local positionThe situations were observed immediately after injection, Group A of drugs looked like the thick oil which was yellow and white under the conjunctiva. Group B of drugs looked pale, white and translucent. Group C of drugs were liquid and transparent under the conjunctiva.2. The swelling degree of conjunctiva after the injection of three drugsGroup A:most swelling degree of the conjunctiva was +++, significant changes occurred on the 14th day,0 eye showed +++. On the 21th,28th day, the swelling of the conjunctiva was still seeing, and there was no significant regression. Group B: most swelling of conjunctiva was ++, the swelling degree of conjunctiva was significantly reduced on the 14th day, and the scope was significantly reduced too. On the 28th day, the swelling of conjunctiva was completely withered up. Group C: most swelling degree of conjunctiva was +, the swelling of the conjunctiva was gradually reduced in 7th day. On the 14th day, the swelling of the conjunctiva was completely subsided.1 d,3 d,7 d the difference rates of the conjunctival swelling among the three groups showed less than 0,05, there was significant difference between the three groups(P<0.05).3. The situation of drug diffuse and degradation and absorptionGroup A:after injection of eye oculentum, on the 3th day, eye oculentum was spreading to the bottom of the ball of the conjunctiva aroudly, but had no significant degradation and absorption. Group B:from the 3th day, eye oculentum was spreading to the blow of subconjunctival tissue, and was gradually degraded and absorbed with the diffusion, on the 28th day, the oculentum was completely absorbed. Group C:the drug was not diffused at each time and was degraded and absorbed at the first day after injection, and it was completely absorbed on 14th day.4. Histopathological changesGroup A:there were inflammatory cells, which were mainly consisted of neutrophil, could be seen in the conjunctival tissue, including lymphocytes, and a large number of fibrous tissue could be seen. The fibrous tissue proliferated and inflammatory cells disappeared on the 21th and 28th day. Group B:there were also inflammatory cells, which were mainly consisted of neutrophil, could be seen in the conjunctival tissue, peripheral vasodilation, had only a small amount of fibrous tissue; on 28th day, conjunctival structure returned to normal. Group C:there were only a small amount of inflammatory cells infiltrated into the conjunctiva tissue, inflammatory cells disappear on 7th day, and have no hyperplastic fibrous tissue, on 14th day, the structure of conjunctiva returned to normal.ConclusionWhen the erythromycin eye oculentum, which takes the vasline, lanolin and liquid paraffin as substrate, was injected into the conjunctival tissue, it would cause the worst inflammatory reaction, therefore, it was not recommended for the tissue of a wound surface.When the ofloxacin eye oculentum, which takes the sodium hyaluronate and carbomer as substrate, was injected into the conjunctival tissue, it would cause slight inflammatory reaction, and it could be used in the lacrimal surgery to play a part in supporting and preventing the tissue to adhesion.The hydroxypropyl methylcellulose did not cause significant inflammatory reaction, but it was not used to inject to the lacrimal because of its low viscosity.更多还原