【作者】 孙亦群；

【导师】 周莉玲； 李锐；

【作者基本信息】 广州中医药大学 ， 中西医结合基础， 2001， 硕士

【摘要】 经皮给药系统（Transdermal Delivery Drug Systym TDDs，orTransdermal Therapeutic Systym，TTS）以其可避免肝脏的“首过效应”和胃肠道的破坏，具有维持稳定、持久的血药浓度，提高生物利用度，毒副作用小，给药方便等明显优势，成为现代制剂研究的热点之一。 九分散是一个传统中药制剂。具活血散瘀、消肿止痛之功效，内服或外用治疗跌打损伤、瘀血肿痛。文献显示，九分散用于治疗痹证疗效显著。但由于处方中有马钱子这一毒性中药，内服易引起中毒，而外敷生物利用度低，因此有必要进行剂改研究。本研究探讨将其制成经度给药制剂九分喷雾剂的可行性。 目的：（1）探讨炮制对乳香、没药挥发油化学成分的影响；（2）筛选九分散提取工艺；（3）建立九分喷雾剂的分析测定方法及透皮吸收实验方法；（4）筛选九分喷雾剂处方；（5）制备九分喷雾剂并进行质量标准研究及其释放行为研究。 方法：（1）采用蒸馏法测定乳香、没药炮制前后挥发油总量的变化，并用气质联用（GC-MS）法分析其化学成分及各成分含量的变化；（2）采用正交试验法及薄层扫描（TLCS）法，从溶剂量、溶剂浓度、提取次数三方面筛选九分散提取工艺；（3）以紫外分光光度法及透皮吸收实验，从四种接收液中筛选接收液；（4）用TLCS法及透皮吸收实验，从19种处方中筛选九分喷雾剂处方；（5）制定九分喷雾剂质量标准，并进行释放率研究。 结果：（1）炮制使乳香、没药挥发油总量有所减少，中低沸点化学成分及各成分含量亦有所减少；二药的生品中挥发油含量 SUNWQUN最高，其化学成分及各成分含量最多，醋制品次之，炒制品最少。（2）经正交实验法优选，得出结论：溶剂量和提取次数对提取有明显影响，最佳提取条件为10倍于药材量的水，提取3次，lhj次。臼）从生理盐水、生理盐水／乙醇门：3，V：V＊PH6．8磷酸盐缓冲沏乙醇（8：2，V：V）、含 25％乙醇的 PH74磷酸盐缓冲液四种接收液中筛选，天内回收率分别为89．37土3．of，101．of士2．66 86．48士2．85，59．44土3．54；天间回收率分别为88．96士2．52，103．09士1．53，90．38士5．61，65．26士2．48；其 Q－T方程分别为牛6．866t＋5．504，Q二17．054t－14．943，Q二10．412t－5．568，Q书．024t－8．672；结果表明，天内及天间回收率和透皮速率常数均以生理盐水／乙醇门：3，V：V）为最高。（4）从19种处方中筛选，以稳定性及喷雾效果为指标，选出四种处方，再以透皮速率为指标筛选，其主要成分士的宁、马钱子碱、盐酸麻黄碱在四种处方中的 QT方程分别为：处方1：小0升人6卜356．18，Qwt6．25t＋68．24，中ZI．167t＋l．254；处方 吕：Q＝65．52t－72．33，Q一9．74！－101．74，e 56．！88n83，905：处方16：中1！3．97【461．95，Q＝9 7．96＊05．75，的5．302p3o．％6：处方互7：Q＝ 139．23饲38刀吕，Q－124．35t－if6．l！，Q－ops．290t＋67．994。从结果可以看出，处方17的稳定性及喷雾效果好，透皮速率最高。6）用TLCS法测定含量，于硅胶OF川薄层板上，以氯仿，甲醇－氨水以mwL）Q：6：！）展开，双波长扫描，士的宁、马钱子碱波长为 入 s二254 urn，人 r二325urn：盐酸麻黄碱波长为人 s二500 n。，入 r＝440un。测定结果：九分喷雾剂主要成分士的宁、马钱子碱、盐酸麻黄碱的天内回收率分别为 99．048士2．388t 99．532土0．958 99．504土0．555；天间回收率分别为 98．796 ti．058，99．58土 0．476，99．42士 0，838：表 4 九分幢经皮给汪制剂的研究明该分析方法稳定可靠。制剂中各成分含量分别为1．474土0．047，1．372上 0．052，1．506土 0．064（n一4）。（6）九分喷雾剂的Q－T 方程分别 为：士的宁 牛220．94lt－486＊06，马钱子碱中208．146t454．629，麻黄碱Q－177．69it·247826；其释放率趋势为：随着时间的延长，累积渗透量增加，释放速率则基本维持稳定，12h的总释药率约为 50％。 结论：乳香、没药以生品入药为宜。九分散提取工艺为10倍于药材量的水，提取3次，lh／次。以生理盐水／乙醇门：3，V：V）为本研究的透皮吸收接收液。九分喷雾剂处方为：样品20％的乙醇液＋3％冰片＋5％甘油。建立九分喷雾剂的TLCS测定方法，该法灵敏、简单，选择性及重复性好，适于九分喷雾剂的经皮渗透研究及质量标准研究。体外研究表明，本制剂所选处方可促进其有效成分的经皮渗透并可维持恒速释药。更多还原

【Abstract】 Jiufen san is a traditional chinese drug. it can anti-inflammation, ease pain and eliminating the stagnant ,activating the blood and relieving the swelling. It is used to cure sprain, contusion and Bi syndromes. However ,it’s toxicity is stronger when it is taken orally. It’s biological utilization ratio is lower when it is applied external.Therefore, it is vary necessary to st’Udy on tr8nsdermal delivery drug(TDD) system of Jiufen san.Objective: (1)TO expiore the infiuence to the chemicalcomPOnents of essential oil in olibanum and myrrha after processing,(2)To select the exhaction Procedure of Jiufen sare (3)TO establish themethods for study on the detCrmination and the PercutaneousPenetraion of the Proparation spraytng of Jiufen, (4)TO oPtimize theprescriPtion of the Proparaion sPIaying of Jiufen, (5)TO Ptepare thepreparahon spraying of Jiufen, (6)TO lay down it’s quality standardand to study it’s reIeasing ruIe.Metbods: Wth distillation method to det6rmine the change ofthe tOta content of essential oil in olibanum and myrrha before andafter processing. Wth GC-MS methed to analyZC the changC of thechemical comPOneme and itS contents of essential oil in olibanum andmyrrha before and affer processing (2) Wth orthogonal design andTLCS methOd tO seleCt the extIaction PrOCedur of Jiufen san. (3) WthUV analysis methOd and the hodermal StUdy tO determine thereceptor suiting for the the PrO~on sPraying of Jiufen. (4) WthTLCS method and the ndermal study of thc the proopionspraying of Jiufen tO seleCt the periPtion of it and tO lay dOwn it’squality standard and tO study it’s the releasing ruIe.Result: (1)The total content of esscntial oil in olibanufn andmyrrha is decrescence after processing The middle and IowerboilPOint chemical components and its cOnents are also dccrescenceafter processing.The content of essential oil and its chcndcal6comPOnents are the most in the two crude thegs, and than in the twodriges that were stir-fried by vinegar and than in the twO stir-fyingdrugS.(2)The volume of solvent and the number of hmes of eXtractionhave notable effect for exthechon. The best conditions are l0 times ofthe herb quanity of waef, extI’act 3 times, l hour Per time .(3) The Q-Tequations of saline, saline / alchol (7f3,vfv),PH6.8 phOsphate buffer/alchol (8t2,v;v),PH7.4 Phosphate buffer content 25% alchol are for6.866t+5.504, Q=17. 054t--l4. 943, Q=10. 4l2t--5. 568,Q=6. 024t--8. 672 respectively, vhich suggest saline / alchol(7;3,vfv) is the best fOr the recePtor. (4) To optimize the bestprescriPtion of the the Proopion spraytng of Jiufen from l9 sorts ofit’s prescriptions by insPecting it’s Stability and the effect of sprayingand the transdermal speed constant (J). The Q-T equations ofstrycbone,brucine, ephedrine in 4 sorts of prescriPtion are fprescriPtion lf Q=l04.46t-356.l8, Q=46.25t+68.24,Q=2l.l67t+l.254: prescriPtion 8: oo5.52t-72.33, Q=59.74t-l0l.74,cy56.188t+83.905: prescriphon l6: cyll3.97t-46l.95,Qeq7.96t-405.75, Q=45.302t+30.766: prescriPtion l7: Q=l39.23t-l38.08, Q=l24.35t-l l6.l l, Q--op8.290t+67.994. Prescription l7 is thebest one. (5) The thin-layer plate is made with silica gel GF,.. Thespread out agent is chlorofOrm- methanol-ammonia solUtion(4momi) (2: 6: l ) .Dual vavelength scan t strycbone and brucine tx s=254 nm, x r=325nm: ephedrinef x s=500 nm, x r=440nm. Thecontent of the Proparation spraytng of Jiufen is l.474 t0. 047, l. 372 f 0. 052, l. 506f0. 064 (n=4 ). The Q-T equation of it’s7is strychninef Q=220.94lt486.006, brucinef Q=208.l46t454.629,ephedrinef Q=177.691t-247.826 .The study on releasing rule suggeststhe accumulative amoam of tusdermal drug increases with time,butthe releasing speed is some steady the total releasing ratio of l2 huorsis about 50 %.ConcIu8ions: Olibanum and myrrha shuold be used with theircrude drugs. The best exthechon procedure are l0 times of the herbquantity of ndef, einct 3 times,更多还原