新目安眼用凝胶剂与目安眼用凝胶剂体外释放及离体角膜渗透性的比较研究
|
摘要
目的：探索更昔洛韦替代阿昔洛韦组成的新目安眼用凝胶剂体外释药、离体角膜渗透性能是否优于原目安眼用凝胶剂。寻找新目安眼用凝胶剂处方组成中蜂蜜的最佳浓度,制定合理的给药方案,为临床治疗单纯疱疹病毒性角膜炎(HSK)提供一种既能抗病毒,又能增加角膜修复、愈合及再生能力且副作用小的新型眼用凝胶剂提供依据。
方法：以稠度、均匀性、涂展性、成型性(柔软性)等为评价指标,采用正交设计试验、等级一致性检验优选基质、添加剂配比、制备工艺参数：建立新目安眼用凝胶剂中更昔洛韦的HPLC含量测定方法,并进行方法学考察：以更昔洛韦含量、阿昔洛韦含量为指标,采用桨法2,进行体外释药实验,建立更昔洛韦体外释药动力学方程,求算释药速度参数和累积释药百分率参数及误差范围,采用95%可信区间重叠法比较新目安眼用凝胶剂与目安眼用凝胶剂释药速度及释药总量的差异：同样以GCV含量、ACV含量为指标,采用Franz扩散池法,进行离体角膜渗透性实验,建立数学模型,通过数学及统计学处理提取角膜渗透性参数,比较新目安眼用凝胶剂与目安眼用凝胶剂渗透速度及渗透总量的差异,比较新目安眼用凝胶剂释药速度与角膜渗透速度的差异、释药总量与角膜渗透总量的差异：通过离体角膜渗透实验,考察含蜂蜜3%、5%、7%的新目安眼用凝胶剂离体角膜渗透速度和角膜渗透总量的差异。
结果：基质、添加剂配比为：PEG4000为1.Og、PEG400为4.0g、聚山梨酯-80为1.5g；最优工艺参数为：GCV与聚山梨酯-80研匀,加蜂蜜研磨,再与PEG400与PEG4000熔融混合液研磨成凝胶剂。新目安眼用凝胶剂中更昔洛韦的HPLC含量测定方法学考察结果表明：标准曲线线性范围、仪器精密度、重复性、稳定性、加样回收率等指标皆满足定量分析要求,阴性无干扰。新目安眼用凝胶剂释药特性等同于目安眼用凝胶剂,释药速度相似,释药量相同,皆达到或满足临床用药要求,给药方案可设计成一日3次,间隔时间6小时～8小时,每次给药每只眼0.1克。新目安眼用凝胶剂角膜渗透特性优于目安眼用凝胶剂(角膜渗透速度是后者的3.452倍,角膜渗透数量是后者的1.832倍),亦优于市售0.15%更昔洛韦眼用凝胶剂(角膜渗透速度是后者的2.029倍),市售0.15%更昔洛韦眼用凝胶剂角膜渗透特性优于市售3%阿昔洛韦眼膏(角膜渗透数量是后者的2.028倍)。按临床眼用半固体制剂给药皆为一日3次,每次每只眼约0.1克,新目安眼用凝胶剂、市售0.15%更昔洛韦眼用凝胶剂皆能满足临床需求,给药次数及间隔时间基本科学、合理、可行,并为下一步药效、毒理、临床研究提供依据。新目安眼用凝胶剂体外释药速度是离体角膜渗透速度的1.336倍;体外释药量是离体角膜渗透量的2.044倍。属于角膜限速型眼用凝胶剂,即释药特性优于角膜渗透特性,凝胶基质及赋型剂对药物释放无影响,能快速将药物释放出来溶解于泪液中发挥治疗作用。含5%蜂蜜的新目安眼用凝胶剂角膜渗透速度是含3%蜂蜜的1.509倍：含7%蜂蜜是含3%蜂蜜的1.483倍;含5%蜂蜜与含7%蜂蜜角膜渗透速度差异无统计学意义;8小时的兔离体角膜累积渗透百分率Y8h(%),含5%蜂蜜等同于含7%蜂蜜,两者皆高于含3%蜂蜜,含5%蜂蜜的新目安眼用凝胶剂角膜渗透量是含3%蜂蜜的1.170倍：含7%蜂蜜是含3%蜂蜜的1.171倍：含5%蜂蜜与含7%蜂蜜角膜渗透量差异无统计学意义,从经济学角度看,应选含5%蜂蜜的新目安眼用凝胶剂。
结论：新目安眼用凝胶剂制备工艺科学、合理、稳定、可行：该制剂中更昔洛韦HPLC含量测定法符合定量分析要求；新目安眼用凝胶剂释药特性等同于目安眼用凝胶剂,角膜渗透特性优于目安眼用凝胶剂；蜂蜜浓度5%最优：新目安眼用凝胶剂属于角膜限速型眼用凝胶剂,释药特性优于角膜渗透特性。更昔洛韦替代阿昔洛韦组成的新目安眼用凝胶剂体外释药、离体角膜渗透性能优于原目安眼用凝胶剂,给药方案为：一日3次,每次每只眼约0.1克,间隔时间6小时～8小时,给药次数及间隔时间基本科学、合理、可行,并为下一步药效、毒理、临床研究提供依据。
Objective:To search the release in vitro of new MU-AN ophthalmic gel consist of Ganciclovir instead of Aciclovir and the permeability of Cornea in Vitro is whether better than the Old. To seek the optimal concentration of the honey in new MU-AN ophthalmic gel prescription, draw down the best dosage regimen, provide a new MU-AN ophthalmic gel that can resists the virus and improve the capabilities of corneal wound healing and regeneration and have less side-effect for clinical to treat Herpes Simplex Keratitis(HSK)
Method:Take consistenc、uniformity、stretchability、 moldability(Flexibility) as the evaluation index, Use orthogonal design test、Level consistency checkout to optimization matrix、the ratio of additives、technological parameter; To establish a method to determine the content of Ganciclovir in new MU-AN ophthalmic gel, and the methodology study was investigated; Use the Ganciclovir、Acyclovir as the index, taking the second Oar Method (in Ch.P2010), drug release in vitro test was investigated, setting up the dynamical equation of Ganciclovir release in vitro, calculating the rate of the drug release in vitro and the total drug release percentage parameter in vitro and the margin of error, take95%Confidence interval superposition method to compare the different between the rate of drug release and the total amount of drug release of new MU-AN ophthalmic gel and the Old. Use the GCV、ACV as the index, too, take the franz diffusion cell method, cornea permeability test in vitro was investigated, setting up mathematical model, disposed of Corneal permeability parameter by Maths and Stat, compare the different between the rate of drug permeate and the total amount of drug permeate of new MU-AN ophthalmic gel and the Old, compare the different between the rate of drug release and the rate of cornea permeate of new MU-AN ophthalmic gel、the different between the total amount of drug release and the total amount of cornea permeate; investigate the different of the rate of drug release and the total amount of cornea permeate of new MU-AN ophthalmic gel consist of3%、5%、7%honey by cornea permeability test in vitro.
Result:The ratio of matrix、additive is that1.Og PEG4000、4.0g PEG400、1.5g Polysorbate-80; The best craft parameter is that mixing GCV with Polysorbate-80、grind with honey、grind with the meltwater combine PEG400with PEG4000. The result of the determination and methodology researching of Ganciclovir by HPLC of new MU-AN ophthalmic gel is that:some index meet the requirements of quantitative analysis, such as standard curve linear range、instrument precision、 repeatability、stability、sample recovery, the blank test showed no interference. The character of drug release of new MU-AN ophthalmic gel is equal to the Old, the rate of drug release is similar. The amount of drug release is the same, Both drugs meet the requirements of clinical medication, the dosage regimen could be designed to three times a day, the interval time is6-8hour, each eye was given0.1g at a time. The character corneal permeability of new MU-AN ophthalmic gel is better than the Old(The rate of corneal permeability is3.452times of the latter,1.832times of the amount of corneal permeability). It is also better than the market0.15%Ganciclovir ophthalmic gel(The rate of corneal permeability is2.029times of the latter). Otherwise, the market0.15%Ganciclovir ophthalmic gel is better than the market3%Acyclovir ophthalmic gel(The amount of corneal permeability is2.028times of the latter).
The drug administration is3times a day accroding to the clinical ophthalmic semisolid preparation, each eye was given0.1g at a time, new MU-AN ophthalmic gel、the market0.15%Ganciclovir ophthalmic gel can meet the requirements of clinical demand, Time Administer Drug and interval time is generally scientific、reasonable、feasible, Providing the basis for the pharmacodynamics, toxicology and clinical study in the next step. The rate of drug release in vitro of new MU-AN ophthalmic gel is1.336times of corneal permeability in vitro; the amount of drug release in vitro is2.044times of corneal permeability in vitro. It is belong to Corneal Rate-limiting ophthalmic gel、the character of drug release is better than corneal permeability, hydrogel matrix and butyl stearate has no influence on drug release, drug would be bring treatment effect after the way that it be released quickly then be dissolved in tear. The rate of corneal permeability of the new MU-AN ophthalmic gel consist of5%honey is1.509times of3%. Similarly,7%is1.483times of3%, the result of compare5%with7%showed no statistically significant; Accumulate Permeate Percentage Y8h (%) of8hours of rabbit corneal in vitro, consist of5%honey is equal to7%, both of them is higher than3%. The amount of corneal permeate of the new MU-AN ophthalmic gel consist of5%honey is1.170times than3%; consist of7%honey is1.171times of3%; the result of compare5%with7%showed no statistically significant too; From the economic view, the new MU-AN ophthalmic gel consist of5%honey should be selected
Conclusion:the preparation craft of new MU-AN ophthalmic gel is scientific、reasonable、stability and feasible; the determination of Ganciclovir by HPLC of this preparation is meet the requirements of quantitative analysis; The character of drug release of new MU-AN ophthalmic gel is equal to the Old, The character of Corneal permeability is better than the Old;5%honey is the best; It is belong to Corneal Rate-limiting ophthalmic gel, the character of drug release is better than corneal permeability. The release in vitro and the character of corneal permeability of new MU-AN ophthalmic gel consist of Ganciclovir instead of Aciclovir is better than the Old, the dosage regimen is that: three times a day, each eye was given0.1g at a time, the interval time is6-8hour, the time administer drug and interval time is generally scientific、reasonable and feasible, providing the basis for the pharmacodynamics, toxicology and clinical study in the next step
方法：以稠度、均匀性、涂展性、成型性(柔软性)等为评价指标,采用正交设计试验、等级一致性检验优选基质、添加剂配比、制备工艺参数：建立新目安眼用凝胶剂中更昔洛韦的HPLC含量测定方法,并进行方法学考察：以更昔洛韦含量、阿昔洛韦含量为指标,采用桨法2,进行体外释药实验,建立更昔洛韦体外释药动力学方程,求算释药速度参数和累积释药百分率参数及误差范围,采用95%可信区间重叠法比较新目安眼用凝胶剂与目安眼用凝胶剂释药速度及释药总量的差异：同样以GCV含量、ACV含量为指标,采用Franz扩散池法,进行离体角膜渗透性实验,建立数学模型,通过数学及统计学处理提取角膜渗透性参数,比较新目安眼用凝胶剂与目安眼用凝胶剂渗透速度及渗透总量的差异,比较新目安眼用凝胶剂释药速度与角膜渗透速度的差异、释药总量与角膜渗透总量的差异：通过离体角膜渗透实验,考察含蜂蜜3%、5%、7%的新目安眼用凝胶剂离体角膜渗透速度和角膜渗透总量的差异。
结果：基质、添加剂配比为：PEG4000为1.Og、PEG400为4.0g、聚山梨酯-80为1.5g；最优工艺参数为：GCV与聚山梨酯-80研匀,加蜂蜜研磨,再与PEG400与PEG4000熔融混合液研磨成凝胶剂。新目安眼用凝胶剂中更昔洛韦的HPLC含量测定方法学考察结果表明：标准曲线线性范围、仪器精密度、重复性、稳定性、加样回收率等指标皆满足定量分析要求,阴性无干扰。新目安眼用凝胶剂释药特性等同于目安眼用凝胶剂,释药速度相似,释药量相同,皆达到或满足临床用药要求,给药方案可设计成一日3次,间隔时间6小时～8小时,每次给药每只眼0.1克。新目安眼用凝胶剂角膜渗透特性优于目安眼用凝胶剂(角膜渗透速度是后者的3.452倍,角膜渗透数量是后者的1.832倍),亦优于市售0.15%更昔洛韦眼用凝胶剂(角膜渗透速度是后者的2.029倍),市售0.15%更昔洛韦眼用凝胶剂角膜渗透特性优于市售3%阿昔洛韦眼膏(角膜渗透数量是后者的2.028倍)。按临床眼用半固体制剂给药皆为一日3次,每次每只眼约0.1克,新目安眼用凝胶剂、市售0.15%更昔洛韦眼用凝胶剂皆能满足临床需求,给药次数及间隔时间基本科学、合理、可行,并为下一步药效、毒理、临床研究提供依据。新目安眼用凝胶剂体外释药速度是离体角膜渗透速度的1.336倍;体外释药量是离体角膜渗透量的2.044倍。属于角膜限速型眼用凝胶剂,即释药特性优于角膜渗透特性,凝胶基质及赋型剂对药物释放无影响,能快速将药物释放出来溶解于泪液中发挥治疗作用。含5%蜂蜜的新目安眼用凝胶剂角膜渗透速度是含3%蜂蜜的1.509倍：含7%蜂蜜是含3%蜂蜜的1.483倍;含5%蜂蜜与含7%蜂蜜角膜渗透速度差异无统计学意义;8小时的兔离体角膜累积渗透百分率Y8h(%),含5%蜂蜜等同于含7%蜂蜜,两者皆高于含3%蜂蜜,含5%蜂蜜的新目安眼用凝胶剂角膜渗透量是含3%蜂蜜的1.170倍：含7%蜂蜜是含3%蜂蜜的1.171倍：含5%蜂蜜与含7%蜂蜜角膜渗透量差异无统计学意义,从经济学角度看,应选含5%蜂蜜的新目安眼用凝胶剂。
结论：新目安眼用凝胶剂制备工艺科学、合理、稳定、可行：该制剂中更昔洛韦HPLC含量测定法符合定量分析要求；新目安眼用凝胶剂释药特性等同于目安眼用凝胶剂,角膜渗透特性优于目安眼用凝胶剂；蜂蜜浓度5%最优：新目安眼用凝胶剂属于角膜限速型眼用凝胶剂,释药特性优于角膜渗透特性。更昔洛韦替代阿昔洛韦组成的新目安眼用凝胶剂体外释药、离体角膜渗透性能优于原目安眼用凝胶剂,给药方案为：一日3次,每次每只眼约0.1克,间隔时间6小时～8小时,给药次数及间隔时间基本科学、合理、可行,并为下一步药效、毒理、临床研究提供依据。
Objective:To search the release in vitro of new MU-AN ophthalmic gel consist of Ganciclovir instead of Aciclovir and the permeability of Cornea in Vitro is whether better than the Old. To seek the optimal concentration of the honey in new MU-AN ophthalmic gel prescription, draw down the best dosage regimen, provide a new MU-AN ophthalmic gel that can resists the virus and improve the capabilities of corneal wound healing and regeneration and have less side-effect for clinical to treat Herpes Simplex Keratitis(HSK)
Method:Take consistenc、uniformity、stretchability、 moldability(Flexibility) as the evaluation index, Use orthogonal design test、Level consistency checkout to optimization matrix、the ratio of additives、technological parameter; To establish a method to determine the content of Ganciclovir in new MU-AN ophthalmic gel, and the methodology study was investigated; Use the Ganciclovir、Acyclovir as the index, taking the second Oar Method (in Ch.P2010), drug release in vitro test was investigated, setting up the dynamical equation of Ganciclovir release in vitro, calculating the rate of the drug release in vitro and the total drug release percentage parameter in vitro and the margin of error, take95%Confidence interval superposition method to compare the different between the rate of drug release and the total amount of drug release of new MU-AN ophthalmic gel and the Old. Use the GCV、ACV as the index, too, take the franz diffusion cell method, cornea permeability test in vitro was investigated, setting up mathematical model, disposed of Corneal permeability parameter by Maths and Stat, compare the different between the rate of drug permeate and the total amount of drug permeate of new MU-AN ophthalmic gel and the Old, compare the different between the rate of drug release and the rate of cornea permeate of new MU-AN ophthalmic gel、the different between the total amount of drug release and the total amount of cornea permeate; investigate the different of the rate of drug release and the total amount of cornea permeate of new MU-AN ophthalmic gel consist of3%、5%、7%honey by cornea permeability test in vitro.
Result:The ratio of matrix、additive is that1.Og PEG4000、4.0g PEG400、1.5g Polysorbate-80; The best craft parameter is that mixing GCV with Polysorbate-80、grind with honey、grind with the meltwater combine PEG400with PEG4000. The result of the determination and methodology researching of Ganciclovir by HPLC of new MU-AN ophthalmic gel is that:some index meet the requirements of quantitative analysis, such as standard curve linear range、instrument precision、 repeatability、stability、sample recovery, the blank test showed no interference. The character of drug release of new MU-AN ophthalmic gel is equal to the Old, the rate of drug release is similar. The amount of drug release is the same, Both drugs meet the requirements of clinical medication, the dosage regimen could be designed to three times a day, the interval time is6-8hour, each eye was given0.1g at a time. The character corneal permeability of new MU-AN ophthalmic gel is better than the Old(The rate of corneal permeability is3.452times of the latter,1.832times of the amount of corneal permeability). It is also better than the market0.15%Ganciclovir ophthalmic gel(The rate of corneal permeability is2.029times of the latter). Otherwise, the market0.15%Ganciclovir ophthalmic gel is better than the market3%Acyclovir ophthalmic gel(The amount of corneal permeability is2.028times of the latter).
The drug administration is3times a day accroding to the clinical ophthalmic semisolid preparation, each eye was given0.1g at a time, new MU-AN ophthalmic gel、the market0.15%Ganciclovir ophthalmic gel can meet the requirements of clinical demand, Time Administer Drug and interval time is generally scientific、reasonable、feasible, Providing the basis for the pharmacodynamics, toxicology and clinical study in the next step. The rate of drug release in vitro of new MU-AN ophthalmic gel is1.336times of corneal permeability in vitro; the amount of drug release in vitro is2.044times of corneal permeability in vitro. It is belong to Corneal Rate-limiting ophthalmic gel、the character of drug release is better than corneal permeability, hydrogel matrix and butyl stearate has no influence on drug release, drug would be bring treatment effect after the way that it be released quickly then be dissolved in tear. The rate of corneal permeability of the new MU-AN ophthalmic gel consist of5%honey is1.509times of3%. Similarly,7%is1.483times of3%, the result of compare5%with7%showed no statistically significant; Accumulate Permeate Percentage Y8h (%) of8hours of rabbit corneal in vitro, consist of5%honey is equal to7%, both of them is higher than3%. The amount of corneal permeate of the new MU-AN ophthalmic gel consist of5%honey is1.170times than3%; consist of7%honey is1.171times of3%; the result of compare5%with7%showed no statistically significant too; From the economic view, the new MU-AN ophthalmic gel consist of5%honey should be selected
Conclusion:the preparation craft of new MU-AN ophthalmic gel is scientific、reasonable、stability and feasible; the determination of Ganciclovir by HPLC of this preparation is meet the requirements of quantitative analysis; The character of drug release of new MU-AN ophthalmic gel is equal to the Old, The character of Corneal permeability is better than the Old;5%honey is the best; It is belong to Corneal Rate-limiting ophthalmic gel, the character of drug release is better than corneal permeability. The release in vitro and the character of corneal permeability of new MU-AN ophthalmic gel consist of Ganciclovir instead of Aciclovir is better than the Old, the dosage regimen is that: three times a day, each eye was given0.1g at a time, the interval time is6-8hour, the time administer drug and interval time is generally scientific、reasonable and feasible, providing the basis for the pharmacodynamics, toxicology and clinical study in the next step
引文
[1]陈祖基.眼科临床药理学[M].北京：化学工业出版社2002：147
[2]高雄伟,李冰.治疗单纯疱疹病毒性角膜炎的新尝试一全身应用更昔洛韦胶囊.中国医疗前沿,2011,(2)：57-58.
[3]严惠芬.更昔洛韦眼用凝胶治疗浅层单疱病毒性角膜炎.医学信息：下旬刊,2011,(6)：160.
[4]卢春富.更昔洛韦眼用凝胶联合干扰素治疗单疱病毒性角膜炎疗效观察.中国现代医生,2011,(11)：128.
[5]徐丽华.更昔洛韦凝胶在带状疱疹病毒性角膜炎中的疗效观察.西南军医,2011,(6)：1054-1055.
[6]古丽努尔·托肯,刘雪清.回顾性分析本院用更昔洛韦与阿昔洛韦治疗单纯疱疹病毒性角膜炎的疗效.中国临床药理学杂志,2011,(6)：425-426.
[7]林体锋,薛圣游,卓文渊等.更昔洛韦眼用凝胶和阿昔洛韦滴眼液治疗单疱性病毒性角膜炎的疗效比较.中国药业,2011,(13)：53-54.
[8]李忠亮,王晓波,宋晓楠.更昔洛韦分散片在健康人体的相对生物利用度与生物等效性.解放军药学学报,2007,(5)：341-344.
[9]张俊杰,高长凤,王丽娅.更昔洛韦原位胶化滴眼液兔眼部药物动力学及生物利用度研究.中华眼科杂志,2006,(7)：637-641.
[10]张嘉声.更昔洛韦眼用凝胶与更昔洛韦滴眼液治疗带状疱疹角膜炎的疗效比较.国际眼科杂志,2011,(2)：309-310.
[11]苏易云,何月枝,温天时.更昔洛韦眼用凝胶联合干扰素治疗单纯疱疹病毒性角膜炎疗效观察.中国当代医药,2010.(18)：53-54.
[12]荆国利,景善雨,周育柱.更昔洛韦眼用凝胶治疗单纯疱疹病毒性角膜炎的临床观察.河南医学研究,2010,(1)：74-75.
[13]Anand BS. In vivo antiviral efficacy of a dipeptide acyclovir prodrug, val-val-acyclovir,against HSV-1 epithelial and stromal keratitis in the rabbit eye model [J]. Invest Ophthalmol Vis Sci.2003 jun;44(6):2529-34
[14]Pavan-Langston D.Pavan-Lanqston. Herpes simplex virus ocular infections:current concepts of acute, latent and reactivated disease [J]. Trans Am Ophthalmol Soc.1990;88:727-96
[15]Heiligenhaus A, Li H, Schmitz A, et al. Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T herper 2 cytokines [J].Clin Exp Immunol.2005 Oct; 142(1):180-7
[16]袁会勇.更昔洛韦眼用凝胶联合干扰素治疗单纯疱疹病毒性角膜炎的疗效分析与评价.临床合理用药杂志,2011,(06X)：43-44.
[17]田艳明,王文强,朱代安,等.蜂蜜胰岛素滴眼对角膜渍疡的疗效观察[J].中国中医眼科杂志.1997,7(2)：133
[18]Hosaka Y. Binding of influenza type A viruses to group B Streptococcus and emagglutination by virus-bound bacteria.J Electron Microsc[J].2000;49(6):765-73
[19]Doughty MJ.Subjective vs. Objective analysis of the corneal endothelial cells in the rabbit cornea by scanning electron microscopy-a comparison of two different methods of corneal fixation [J].J Vet Ophthalmol.2006 Mar-Apr; 9 (2):127-35.
[20]Pancheva. SN. Potentiating effect of ribavirin in the anti-herpes activity of acyclovir [J].Antiviral Res.1991;16:151-161.
[21]庞松然.更昔洛韦眼用凝胶联合维生素C、糖皮质激素球结膜下注射治疗角膜内皮炎的临床研究. 中国医药指南,2011,(21)：302-304.
[22]顾桂秋,张西果,赵如慧等.更昔洛韦分散片的处方工艺研究.中国现代临床医学,2005,(5)：1—2.
[23]李孝东,陈智金,张娜等.更昔洛韦β-环糊精包合物制备.中国医院药学杂志,2008,(23)：2019-2021.
[24]徐红蓉,李雪宁,陈伟力,等.液相色谱一串联质谱法测定缬更昔洛韦血药浓度及其在健康人体的药代动力学研究[J].中国临床药理学杂志,2007,23(3)：205-208.
[25]肖岚,朱荣华,李宏亮等.高效液相色谱法测定血浆中更昔洛 韦及其生物等效性.中南药学,2006,(3)：184-186.
[26]石翠斌,白小红,姜丽芳,等.HPLC法同时快速测定血浆中更昔洛韦、阿昔洛韦和喷昔洛韦的浓度.药物分析杂志,2006,(9)：1199-1203.
[27]史桂玲,刘杰.HPLC法测定更昔洛韦血药浓度.天津药学,2006,(4)：40-41.
[28]常珍,曹桂芳,高雷,等.更昔洛韦含量及有关物质的HPLC测定.药物分析杂志,2005,(9)：1058-1060.
[29]曹海.更昔洛韦的HPLC测定.黑龙江医药,2004,(1)：12-13.
[30]王茂义,苏华.RP—HPLC法测定更昔洛韦血清浓度.西安医科大学学报,1999,(4)：571-572.
[31]吴畏,孟德胜.更昔洛韦在犬体内血药浓度的测定及其分散片的相对生物利用度研究.中国药房,2010,(5)：420-422.
[32]沈雁,涂家生,陆洋,等.更昔洛韦滴眼液在家兔房水内的药物浓度测定及其药动学特征. 中国临床药学杂志,2007,(4)：199-203.
[33]张俊杰,高长凤,王丽娅.更昔洛韦原位胶化滴眼液兔眼部药物动力学及生物利用度研究.中华眼科杂志,2006,(7)：637-641.
[34]丁蓉,潘柏良.更昔洛韦肺部靶向微囊的制备及体外释放度测定.中国药房,2008,(31)：2447-2448.
[35]林风云,罗易,朱照静.更昔洛韦超声定位靶向释药微囊的制备与体外释药.中国医院药学杂志,2010,(9)：765—768.
[36]熊增慧,吴海燕.更昔洛韦在家兔体内药动学研究.中国药学杂志,1996,(12)：739-742.
[37]张嘉声.更昔洛韦滴眼液联合炎琥宁治疗单纯疱疹病毒性角膜炎的疗效观察.国际眼科杂志,2011(2)：309-310.
[1]徐彦,潘立群,施义,贾晓斌,兰雪莲,陈德轩.温度敏感型盐酸川芎嗪腹腔用原位缓释凝胶的制备研究与评价[J].时珍国医国药,2007,18(5)：1068-1070。
[2]魏刚,陆丽芳,钟高仁,丁佳,陆伟跃.温度敏感型原位凝胶用于蛋白类药物缓释注射给药系统的初步研究[J].中国医药工业杂志,2006,37(9)：597-601。
[3]高琳雁,李桂玲,邓丽娟,丁维明,李眉.温度敏感原位凝胶在眼部给药系统中的研究进展[J].中国抗生素杂志,2009,34(3)：142-147。
[4]魏刚,陆伟跃,郑俊民.温度敏感原位凝胶中药物的扩散行为[J].药学学报,2004,39(3)：232-235。
[5]马守伟,甘勇,甘莉,朱春柳,朱家壁.新型眼用阳离子微乳-原位凝胶的制备及其体外角膜滞留特性的研究[J].药学学报,2008,43(7)：749-755。
[6]陈立亚.眼用即型凝胶的特点及质量控制[J].药学实践杂志,2007,25(4)：193-195,226。
[7]李素霞,曹德英,王刚.眼用即型凝胶的研究进展[J].中国医院药学杂志,2008,28(3)：228-230。
[8]卢亚欣,何海冰,崔越,唐星.乙酸异丁酸蔗糖酯原位凝胶流变学性质的研究[J].药学学报,2007,42(4)：445-449。
[9]崔海珍,刘福强,王艳萍,赵楠,李予严.银杏叶鼻用原位凝胶 的制备及体外吸收研究[J].药学实践杂志,2010,28(2)：118-121。
[10]仇海镇,李娟.原位凝胶的研究进展及其在药剂学中的应用[J].医学信息,2010,23(4)：1524-1526。
[11]孙海燕,杜兴,沙红玉.原位凝胶在滴眼剂中的研究进展[J].综述报告,2005,14(8)：90-91。
[12]王艳,王柏.原位凝胶在滴眼剂应用[J].药学专论,2008,17(6)：19-21。
[13]代龙.珍珠明目眼用即型凝胶的质量标准研究[J].齐鲁药事,2008,27(12)：726-729。
[14]Mengping Zhou, Maureen D, Donovan. Intranasal mucociliary clearance of putative bioadhesive polymer gels [J]. Int J Pharm.1996.135(1-2):115-125.
[15]yim Z, Zupon MA, Chaudry I A. Stable oleaginous gel, US Pat.4851220,25 July 1989.
[16]Moghimi SM. Opsono-recognition of liposomes by tissue macrophages [J] Int J Pharm.1998.162(1-2):11-18.
[17]Allen C. Eisenberg A, Maysinger D. Nano engineering block eopolymer aggregates for drug delivery[J]. Colloids Surfaces B; Biointerfaces,1999,16 (1-4):3.
[18]Bhauarai N, Ramay HR, Gunn J. el a1. PEG-grafted chitosan as an injectable thermosensitive hydrogcl for sustained protein release [J]. J Controlled Release, 2005,103(3): 609-624.
[19]Zenter GM, Rathi R, Shin CH, el a1. Biodegradable block copolymers for delivery of proteins and water insoluble drugs[J]. J Controlled Release,2001,72(2-3):203-215.
[20]Yah ZHAO, Peng YUE, Tao TAO, Qing-hua CHEN. Drug brain distribution following intranasal administration of Huperzine A in situ gel in rats [J]. Acta Pharmacol Sin,2007,28 (2): 273-278。
[21]Shi-1ei CAO, Qi-zhi ZHANG, Xin-guo JIANG. Preparation of ion-activated in situ gel systems of scopolamine hydrobromide and evaluation of its antimotion sickness efficacy [J]. Acta Pharmacol Si,2007,28 (4):584-590。
[22]张治强,张玮,陈光,张敏,霍俊滨,崔磊,楚皓文,高静.pH敏感型盐酸左氧氟沙星眼用即型凝胶的制备及其体外释放考察[J].药学实践杂志,2010,28(2)：122-125。
[23]朱海彦,杨凤霞.pH敏感型原位凝胶的研究进展[J].齐鲁药事,2006,25(8)：486-488。
[24]陈丽娜,李东,谢静,廖朝峰.阿奇霉素眼用即型凝胶的稳定性研究[J].中国现代药物应用,2010,4(8)：12-14。
[25]马文狄,潘卫三,徐晖,聂淑芳,张立婷,郑俊民.丙烯酸一Pluronic F127接枝共聚物的流变学性质[J].沈阳药科大学学报,2007,24(3)：129-132。
[26]徐晖,王绍宁,周力民,冯彩霞,唐星,郑俊民.丙烯酸一泊洛沙姆407共聚物的合成及其原位胶凝性质[J].沈阳药科大学学报,2006,23(7)：421-424。
[27]李欣宇,朱照静,程安媛.地塞米松磷酸钠温度敏感原位凝胶的特性研究[J].药学学报,2008,43(2)：208-213。
[28]张俊明,李良,郑国安,郭晟,丁琦.复方熊胆眼用即型凝胶局部眼刺激性试验[J].内蒙古中医药,2009,(12)：61-62。
[29]孙达,王启龙,潘俊芳,张朝晖.格拉司琼原位凝胶注射剂的体内释药研究[J].时珍国医国药,2010,21(7)：1808-1809。
[30]陈钢,侯世祥,刘军,栾建刚,张瑜.鼓室注射地塞米松原位凝胶的体内分布及药动学研究[J].四川大学学报(医学版),2006,37(3)：456-459。
[31]宋成君,王莹,王春艳,田蕾,刘艳君,张瑞斌.黄芩温度敏感凝胶剂的研究[J].中国中药杂志,2008,33(6)：628—631。
[32]徐亚静,胡容峰,尹辉,高宇.加替沙星pH敏感眼用原位凝胶体外释放的研究[J].中国生化药物杂志,2010,31(2)：107-110。
[33]修佳.甲磺酸帕珠沙星即型凝胶滴眼剂的制备及质量控制[J].临床医学,2008,28(8)：108-110。
[34]姜芳宁,刘效栓,刘光斌.甲磺酸帕珠沙星眼用即型凝胶的制备及质量控制[J]. 中国实用医药,2010,5(11)：14-15。
[35]王丽娟,朱照静,吴青,马俐丽.均匀设计法优选布洛芬缓释原位凝胶剂处方及释药性质的研究[J].重庆医科大学学报,2009,34 (12)：1704-1708。
[36]杨琳,张永萍.均匀设计法优选盐酸麻黄碱穴位注射植入原位凝胶的处方[J].贵阳中医学院学报,2009,(5)：62-65。
[37]任晓维,曹师磊,陈钧,陈恩,蒋新国.糠酸莫米松鼻用即型凝胶剂的稳定性研究[J].安徽医药,2008,12(12)：1144-1146。
[38]任晓维,曹师磊, 陈钧, 陈恩, 蒋新国.糠酸莫米松鼻用即型凝胶剂的制备及质量评价[J].复旦学报(医学版),2008,35(5)：707-710。
[39]徐玉红,李东,王蔓琳,李玉珍,何文.壳聚糖对温敏性原位凝胶基质体外流变学特性的影响[J].药物研究(医学版),2007,16(18)：4-5。
[40]孙绍华,曹辉,苏海佳,谭天伟.可注射原位凝胶的制备及性能表征[J].材料导报：研究篇,2009,23(7)：109-112。
[41]孔志峰,郝吉福,郭丰广,孝建华,王建筑,张雯.氯霉素温敏型眼用原位凝胶的研制[J].中国生化药物杂志,2010,31(3)：185-189。
[42]朱海彦,崔福德.尼群地平可生物降解微球和原位凝胶的药物动力学[J].沈阳药科大学学报,2007,24(3)：133-137,176。
[43]邓丽娟,李桂玲,丁维明,李眉.喷昔洛韦眼用温度敏感原位凝胶的制备及质量控制[J].中国抗生素杂志,2010,35(6)：457-461。
[44]肖春雷,朱家壁,孙超.氢澳酸高乌甲素鼻用原位凝胶剂的制备及其处方评价[J].药学进展,2009,33(9)：416-419。
[45]张建强,杨放,姚洁,李蔷薇,何正有,邓小宽,陈书峰,金英华,刘君焱,胡杨洋.乳酸环丙沙星眼用即型凝胶的研制[J].中国抗生素杂志,2010,35(4)：292-295,313。
[46]陶涛,赵雁,岳鹏,董文心,陈庆华.石杉碱甲鼻用原位凝胶的制备及其经鼻脑靶向性评价[J].药学学报,2006,41(11)：1104-1110。
[47]蔡铮,侯世祥,杨兆祥,宋相容,陈秋红,李元波,赵斌斌.天麻素鼻用原位凝胶脑靶向性研究[J].四川大学学报(医学版),2008,39(3)：438-440。
[48]蔡铮,侯世祥,宋相容,杨兆祥,郑璃,赵斌斌.天麻素离子敏感鼻用原位凝胶体外释药研究[J].中国中药杂志,2008,33(7)：760-762。
[2]高雄伟,李冰.治疗单纯疱疹病毒性角膜炎的新尝试一全身应用更昔洛韦胶囊.中国医疗前沿,2011,(2)：57-58.
[3]严惠芬.更昔洛韦眼用凝胶治疗浅层单疱病毒性角膜炎.医学信息：下旬刊,2011,(6)：160.
[4]卢春富.更昔洛韦眼用凝胶联合干扰素治疗单疱病毒性角膜炎疗效观察.中国现代医生,2011,(11)：128.
[5]徐丽华.更昔洛韦凝胶在带状疱疹病毒性角膜炎中的疗效观察.西南军医,2011,(6)：1054-1055.
[6]古丽努尔·托肯,刘雪清.回顾性分析本院用更昔洛韦与阿昔洛韦治疗单纯疱疹病毒性角膜炎的疗效.中国临床药理学杂志,2011,(6)：425-426.
[7]林体锋,薛圣游,卓文渊等.更昔洛韦眼用凝胶和阿昔洛韦滴眼液治疗单疱性病毒性角膜炎的疗效比较.中国药业,2011,(13)：53-54.
[8]李忠亮,王晓波,宋晓楠.更昔洛韦分散片在健康人体的相对生物利用度与生物等效性.解放军药学学报,2007,(5)：341-344.
[9]张俊杰,高长凤,王丽娅.更昔洛韦原位胶化滴眼液兔眼部药物动力学及生物利用度研究.中华眼科杂志,2006,(7)：637-641.
[10]张嘉声.更昔洛韦眼用凝胶与更昔洛韦滴眼液治疗带状疱疹角膜炎的疗效比较.国际眼科杂志,2011,(2)：309-310.
[11]苏易云,何月枝,温天时.更昔洛韦眼用凝胶联合干扰素治疗单纯疱疹病毒性角膜炎疗效观察.中国当代医药,2010.(18)：53-54.
[12]荆国利,景善雨,周育柱.更昔洛韦眼用凝胶治疗单纯疱疹病毒性角膜炎的临床观察.河南医学研究,2010,(1)：74-75.
[13]Anand BS. In vivo antiviral efficacy of a dipeptide acyclovir prodrug, val-val-acyclovir,against HSV-1 epithelial and stromal keratitis in the rabbit eye model [J]. Invest Ophthalmol Vis Sci.2003 jun;44(6):2529-34
[14]Pavan-Langston D.Pavan-Lanqston. Herpes simplex virus ocular infections:current concepts of acute, latent and reactivated disease [J]. Trans Am Ophthalmol Soc.1990;88:727-96
[15]Heiligenhaus A, Li H, Schmitz A, et al. Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T herper 2 cytokines [J].Clin Exp Immunol.2005 Oct; 142(1):180-7
[16]袁会勇.更昔洛韦眼用凝胶联合干扰素治疗单纯疱疹病毒性角膜炎的疗效分析与评价.临床合理用药杂志,2011,(06X)：43-44.
[17]田艳明,王文强,朱代安,等.蜂蜜胰岛素滴眼对角膜渍疡的疗效观察[J].中国中医眼科杂志.1997,7(2)：133
[18]Hosaka Y. Binding of influenza type A viruses to group B Streptococcus and emagglutination by virus-bound bacteria.J Electron Microsc[J].2000;49(6):765-73
[19]Doughty MJ.Subjective vs. Objective analysis of the corneal endothelial cells in the rabbit cornea by scanning electron microscopy-a comparison of two different methods of corneal fixation [J].J Vet Ophthalmol.2006 Mar-Apr; 9 (2):127-35.
[20]Pancheva. SN. Potentiating effect of ribavirin in the anti-herpes activity of acyclovir [J].Antiviral Res.1991;16:151-161.
[21]庞松然.更昔洛韦眼用凝胶联合维生素C、糖皮质激素球结膜下注射治疗角膜内皮炎的临床研究. 中国医药指南,2011,(21)：302-304.
[22]顾桂秋,张西果,赵如慧等.更昔洛韦分散片的处方工艺研究.中国现代临床医学,2005,(5)：1—2.
[23]李孝东,陈智金,张娜等.更昔洛韦β-环糊精包合物制备.中国医院药学杂志,2008,(23)：2019-2021.
[24]徐红蓉,李雪宁,陈伟力,等.液相色谱一串联质谱法测定缬更昔洛韦血药浓度及其在健康人体的药代动力学研究[J].中国临床药理学杂志,2007,23(3)：205-208.
[25]肖岚,朱荣华,李宏亮等.高效液相色谱法测定血浆中更昔洛 韦及其生物等效性.中南药学,2006,(3)：184-186.
[26]石翠斌,白小红,姜丽芳,等.HPLC法同时快速测定血浆中更昔洛韦、阿昔洛韦和喷昔洛韦的浓度.药物分析杂志,2006,(9)：1199-1203.
[27]史桂玲,刘杰.HPLC法测定更昔洛韦血药浓度.天津药学,2006,(4)：40-41.
[28]常珍,曹桂芳,高雷,等.更昔洛韦含量及有关物质的HPLC测定.药物分析杂志,2005,(9)：1058-1060.
[29]曹海.更昔洛韦的HPLC测定.黑龙江医药,2004,(1)：12-13.
[30]王茂义,苏华.RP—HPLC法测定更昔洛韦血清浓度.西安医科大学学报,1999,(4)：571-572.
[31]吴畏,孟德胜.更昔洛韦在犬体内血药浓度的测定及其分散片的相对生物利用度研究.中国药房,2010,(5)：420-422.
[32]沈雁,涂家生,陆洋,等.更昔洛韦滴眼液在家兔房水内的药物浓度测定及其药动学特征. 中国临床药学杂志,2007,(4)：199-203.
[33]张俊杰,高长凤,王丽娅.更昔洛韦原位胶化滴眼液兔眼部药物动力学及生物利用度研究.中华眼科杂志,2006,(7)：637-641.
[34]丁蓉,潘柏良.更昔洛韦肺部靶向微囊的制备及体外释放度测定.中国药房,2008,(31)：2447-2448.
[35]林风云,罗易,朱照静.更昔洛韦超声定位靶向释药微囊的制备与体外释药.中国医院药学杂志,2010,(9)：765—768.
[36]熊增慧,吴海燕.更昔洛韦在家兔体内药动学研究.中国药学杂志,1996,(12)：739-742.
[37]张嘉声.更昔洛韦滴眼液联合炎琥宁治疗单纯疱疹病毒性角膜炎的疗效观察.国际眼科杂志,2011(2)：309-310.
[1]徐彦,潘立群,施义,贾晓斌,兰雪莲,陈德轩.温度敏感型盐酸川芎嗪腹腔用原位缓释凝胶的制备研究与评价[J].时珍国医国药,2007,18(5)：1068-1070。
[2]魏刚,陆丽芳,钟高仁,丁佳,陆伟跃.温度敏感型原位凝胶用于蛋白类药物缓释注射给药系统的初步研究[J].中国医药工业杂志,2006,37(9)：597-601。
[3]高琳雁,李桂玲,邓丽娟,丁维明,李眉.温度敏感原位凝胶在眼部给药系统中的研究进展[J].中国抗生素杂志,2009,34(3)：142-147。
[4]魏刚,陆伟跃,郑俊民.温度敏感原位凝胶中药物的扩散行为[J].药学学报,2004,39(3)：232-235。
[5]马守伟,甘勇,甘莉,朱春柳,朱家壁.新型眼用阳离子微乳-原位凝胶的制备及其体外角膜滞留特性的研究[J].药学学报,2008,43(7)：749-755。
[6]陈立亚.眼用即型凝胶的特点及质量控制[J].药学实践杂志,2007,25(4)：193-195,226。
[7]李素霞,曹德英,王刚.眼用即型凝胶的研究进展[J].中国医院药学杂志,2008,28(3)：228-230。
[8]卢亚欣,何海冰,崔越,唐星.乙酸异丁酸蔗糖酯原位凝胶流变学性质的研究[J].药学学报,2007,42(4)：445-449。
[9]崔海珍,刘福强,王艳萍,赵楠,李予严.银杏叶鼻用原位凝胶 的制备及体外吸收研究[J].药学实践杂志,2010,28(2)：118-121。
[10]仇海镇,李娟.原位凝胶的研究进展及其在药剂学中的应用[J].医学信息,2010,23(4)：1524-1526。
[11]孙海燕,杜兴,沙红玉.原位凝胶在滴眼剂中的研究进展[J].综述报告,2005,14(8)：90-91。
[12]王艳,王柏.原位凝胶在滴眼剂应用[J].药学专论,2008,17(6)：19-21。
[13]代龙.珍珠明目眼用即型凝胶的质量标准研究[J].齐鲁药事,2008,27(12)：726-729。
[14]Mengping Zhou, Maureen D, Donovan. Intranasal mucociliary clearance of putative bioadhesive polymer gels [J]. Int J Pharm.1996.135(1-2):115-125.
[15]yim Z, Zupon MA, Chaudry I A. Stable oleaginous gel, US Pat.4851220,25 July 1989.
[16]Moghimi SM. Opsono-recognition of liposomes by tissue macrophages [J] Int J Pharm.1998.162(1-2):11-18.
[17]Allen C. Eisenberg A, Maysinger D. Nano engineering block eopolymer aggregates for drug delivery[J]. Colloids Surfaces B; Biointerfaces,1999,16 (1-4):3.
[18]Bhauarai N, Ramay HR, Gunn J. el a1. PEG-grafted chitosan as an injectable thermosensitive hydrogcl for sustained protein release [J]. J Controlled Release, 2005,103(3): 609-624.
[19]Zenter GM, Rathi R, Shin CH, el a1. Biodegradable block copolymers for delivery of proteins and water insoluble drugs[J]. J Controlled Release,2001,72(2-3):203-215.
[20]Yah ZHAO, Peng YUE, Tao TAO, Qing-hua CHEN. Drug brain distribution following intranasal administration of Huperzine A in situ gel in rats [J]. Acta Pharmacol Sin,2007,28 (2): 273-278。
[21]Shi-1ei CAO, Qi-zhi ZHANG, Xin-guo JIANG. Preparation of ion-activated in situ gel systems of scopolamine hydrobromide and evaluation of its antimotion sickness efficacy [J]. Acta Pharmacol Si,2007,28 (4):584-590。
[22]张治强,张玮,陈光,张敏,霍俊滨,崔磊,楚皓文,高静.pH敏感型盐酸左氧氟沙星眼用即型凝胶的制备及其体外释放考察[J].药学实践杂志,2010,28(2)：122-125。
[23]朱海彦,杨凤霞.pH敏感型原位凝胶的研究进展[J].齐鲁药事,2006,25(8)：486-488。
[24]陈丽娜,李东,谢静,廖朝峰.阿奇霉素眼用即型凝胶的稳定性研究[J].中国现代药物应用,2010,4(8)：12-14。
[25]马文狄,潘卫三,徐晖,聂淑芳,张立婷,郑俊民.丙烯酸一Pluronic F127接枝共聚物的流变学性质[J].沈阳药科大学学报,2007,24(3)：129-132。
[26]徐晖,王绍宁,周力民,冯彩霞,唐星,郑俊民.丙烯酸一泊洛沙姆407共聚物的合成及其原位胶凝性质[J].沈阳药科大学学报,2006,23(7)：421-424。
[27]李欣宇,朱照静,程安媛.地塞米松磷酸钠温度敏感原位凝胶的特性研究[J].药学学报,2008,43(2)：208-213。
[28]张俊明,李良,郑国安,郭晟,丁琦.复方熊胆眼用即型凝胶局部眼刺激性试验[J].内蒙古中医药,2009,(12)：61-62。
[29]孙达,王启龙,潘俊芳,张朝晖.格拉司琼原位凝胶注射剂的体内释药研究[J].时珍国医国药,2010,21(7)：1808-1809。
[30]陈钢,侯世祥,刘军,栾建刚,张瑜.鼓室注射地塞米松原位凝胶的体内分布及药动学研究[J].四川大学学报(医学版),2006,37(3)：456-459。
[31]宋成君,王莹,王春艳,田蕾,刘艳君,张瑞斌.黄芩温度敏感凝胶剂的研究[J].中国中药杂志,2008,33(6)：628—631。
[32]徐亚静,胡容峰,尹辉,高宇.加替沙星pH敏感眼用原位凝胶体外释放的研究[J].中国生化药物杂志,2010,31(2)：107-110。
[33]修佳.甲磺酸帕珠沙星即型凝胶滴眼剂的制备及质量控制[J].临床医学,2008,28(8)：108-110。
[34]姜芳宁,刘效栓,刘光斌.甲磺酸帕珠沙星眼用即型凝胶的制备及质量控制[J]. 中国实用医药,2010,5(11)：14-15。
[35]王丽娟,朱照静,吴青,马俐丽.均匀设计法优选布洛芬缓释原位凝胶剂处方及释药性质的研究[J].重庆医科大学学报,2009,34 (12)：1704-1708。
[36]杨琳,张永萍.均匀设计法优选盐酸麻黄碱穴位注射植入原位凝胶的处方[J].贵阳中医学院学报,2009,(5)：62-65。
[37]任晓维,曹师磊,陈钧,陈恩,蒋新国.糠酸莫米松鼻用即型凝胶剂的稳定性研究[J].安徽医药,2008,12(12)：1144-1146。
[38]任晓维,曹师磊, 陈钧, 陈恩, 蒋新国.糠酸莫米松鼻用即型凝胶剂的制备及质量评价[J].复旦学报(医学版),2008,35(5)：707-710。
[39]徐玉红,李东,王蔓琳,李玉珍,何文.壳聚糖对温敏性原位凝胶基质体外流变学特性的影响[J].药物研究(医学版),2007,16(18)：4-5。
[40]孙绍华,曹辉,苏海佳,谭天伟.可注射原位凝胶的制备及性能表征[J].材料导报：研究篇,2009,23(7)：109-112。
[41]孔志峰,郝吉福,郭丰广,孝建华,王建筑,张雯.氯霉素温敏型眼用原位凝胶的研制[J].中国生化药物杂志,2010,31(3)：185-189。
[42]朱海彦,崔福德.尼群地平可生物降解微球和原位凝胶的药物动力学[J].沈阳药科大学学报,2007,24(3)：133-137,176。
[43]邓丽娟,李桂玲,丁维明,李眉.喷昔洛韦眼用温度敏感原位凝胶的制备及质量控制[J].中国抗生素杂志,2010,35(6)：457-461。
[44]肖春雷,朱家壁,孙超.氢澳酸高乌甲素鼻用原位凝胶剂的制备及其处方评价[J].药学进展,2009,33(9)：416-419。
[45]张建强,杨放,姚洁,李蔷薇,何正有,邓小宽,陈书峰,金英华,刘君焱,胡杨洋.乳酸环丙沙星眼用即型凝胶的研制[J].中国抗生素杂志,2010,35(4)：292-295,313。
[46]陶涛,赵雁,岳鹏,董文心,陈庆华.石杉碱甲鼻用原位凝胶的制备及其经鼻脑靶向性评价[J].药学学报,2006,41(11)：1104-1110。
[47]蔡铮,侯世祥,杨兆祥,宋相容,陈秋红,李元波,赵斌斌.天麻素鼻用原位凝胶脑靶向性研究[J].四川大学学报(医学版),2008,39(3)：438-440。
[48]蔡铮,侯世祥,宋相容,杨兆祥,郑璃,赵斌斌.天麻素离子敏感鼻用原位凝胶体外释药研究[J].中国中药杂志,2008,33(7)：760-762。