中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2012年
11期
968-971
,共4页
郭梦翔%朱晓波%王延东%马伟%唐仕波
郭夢翔%硃曉波%王延東%馬偉%唐仕波
곽몽상%주효파%왕연동%마위%당사파
银杏内酯B%药剂学/自微乳化释药系统%高效液相-电喷雾-质谱联用%药代动力学
銀杏內酯B%藥劑學/自微乳化釋藥繫統%高效液相-電噴霧-質譜聯用%藥代動力學
은행내지B%약제학/자미유화석약계통%고효액상-전분무-질보련용%약대동역학
Ginkgolide B%Pharmacy/Self micro emulsifying drug delivery system%High performance liquid chromatography-electrospray ionization-mass spectrum%Pharmacokinetics
背景 银杏内酯B(GB)具有明确的神经保护和抗凋亡作用,可以有效拮抗视网膜内感光细胞的凋亡,达到治疗视网膜变性类疾病的目的,但GB的高疏水性和低生物利用度限制了其临床应用.自微乳化释药系统(SMEDDS)能有效提高难溶性药物的溶出度和生物利用度,因此可能提高GB在视网膜中的生物利用度. 目的研究自制GB-SMEDDS灌胃后在SD大鼠视网膜内的药代动力学及药时变化. 方法 采用随机数字表法将80只SD大鼠分为GB混悬液组和GB-SMEDDS组2个组,每组40只,分别给予40 mg/kg自制质量分数2.5% GB-SMEDDS或GB混悬液(质量分数0.1% DMSO溶解)灌胃,并于给药后15、30、45 min和1、2、4、8、12h分别处死5只大鼠,解剖显微镜下分离大鼠视网膜,制备大鼠视网膜上清液,经高效液相-电喷雾离子-质谱联用(HPLC-ESI-MS)法检测GB的质量浓度,并与标准曲线对比换算,药代动力学参数采用实用药物动力学程序3p87中的统计矩方法计算,计算出视网膜中的最大药物质量分数(Cmax,mg/g)、药物达峰时间(Tmax,h)、清除率(Ke/h)、吸收半衰期(t1/2)和药时曲线下面积[AUC0-∞,mg/(g·h)]. 结果 GB在1~ 32 mg/L时线性关系良好,线性回归方程为Y=0.0732X+0.056(r=0.992).GB-SMEDDS组和GB混悬液组大鼠灌胃后有着相似的药时曲线,但是除了给药后15 min视网膜中的药物质量分数两者一致外,其他各个时间点GB-SMEDDS组视网膜内药物质量分数均高于GB混悬液组.两组大鼠视网膜中Cmax分别为(15.83±1.84) mg/g和(2.65±0.10) mg/g,AUC0-∞分别为(15.30±0.11)mg/(g·h)和(6.42±0.19)mg/(g·h). 结论 HPLC-ESI-MS具有快速、准确、灵敏度高的特点,适合GB制剂在SD大鼠视网膜中药代动力学的研究.SMEDDS可以显著提高GB在视网膜中的含量,可能提高其生物利用度.
揹景 銀杏內酯B(GB)具有明確的神經保護和抗凋亡作用,可以有效拮抗視網膜內感光細胞的凋亡,達到治療視網膜變性類疾病的目的,但GB的高疏水性和低生物利用度限製瞭其臨床應用.自微乳化釋藥繫統(SMEDDS)能有效提高難溶性藥物的溶齣度和生物利用度,因此可能提高GB在視網膜中的生物利用度. 目的研究自製GB-SMEDDS灌胃後在SD大鼠視網膜內的藥代動力學及藥時變化. 方法 採用隨機數字錶法將80隻SD大鼠分為GB混懸液組和GB-SMEDDS組2箇組,每組40隻,分彆給予40 mg/kg自製質量分數2.5% GB-SMEDDS或GB混懸液(質量分數0.1% DMSO溶解)灌胃,併于給藥後15、30、45 min和1、2、4、8、12h分彆處死5隻大鼠,解剖顯微鏡下分離大鼠視網膜,製備大鼠視網膜上清液,經高效液相-電噴霧離子-質譜聯用(HPLC-ESI-MS)法檢測GB的質量濃度,併與標準麯線對比換算,藥代動力學參數採用實用藥物動力學程序3p87中的統計矩方法計算,計算齣視網膜中的最大藥物質量分數(Cmax,mg/g)、藥物達峰時間(Tmax,h)、清除率(Ke/h)、吸收半衰期(t1/2)和藥時麯線下麵積[AUC0-∞,mg/(g·h)]. 結果 GB在1~ 32 mg/L時線性關繫良好,線性迴歸方程為Y=0.0732X+0.056(r=0.992).GB-SMEDDS組和GB混懸液組大鼠灌胃後有著相似的藥時麯線,但是除瞭給藥後15 min視網膜中的藥物質量分數兩者一緻外,其他各箇時間點GB-SMEDDS組視網膜內藥物質量分數均高于GB混懸液組.兩組大鼠視網膜中Cmax分彆為(15.83±1.84) mg/g和(2.65±0.10) mg/g,AUC0-∞分彆為(15.30±0.11)mg/(g·h)和(6.42±0.19)mg/(g·h). 結論 HPLC-ESI-MS具有快速、準確、靈敏度高的特點,適閤GB製劑在SD大鼠視網膜中藥代動力學的研究.SMEDDS可以顯著提高GB在視網膜中的含量,可能提高其生物利用度.
배경 은행내지B(GB)구유명학적신경보호화항조망작용,가이유효길항시망막내감광세포적조망,체도치료시망막변성류질병적목적,단GB적고소수성화저생물이용도한제료기림상응용.자미유화석약계통(SMEDDS)능유효제고난용성약물적용출도화생물이용도,인차가능제고GB재시망막중적생물이용도. 목적연구자제GB-SMEDDS관위후재SD대서시망막내적약대동역학급약시변화. 방법 채용수궤수자표법장80지SD대서분위GB혼현액조화GB-SMEDDS조2개조,매조40지,분별급여40 mg/kg자제질량분수2.5% GB-SMEDDS혹GB혼현액(질량분수0.1% DMSO용해)관위,병우급약후15、30、45 min화1、2、4、8、12h분별처사5지대서,해부현미경하분리대서시망막,제비대서시망막상청액,경고효액상-전분무리자-질보련용(HPLC-ESI-MS)법검측GB적질량농도,병여표준곡선대비환산,약대동역학삼수채용실용약물동역학정서3p87중적통계구방법계산,계산출시망막중적최대약물질량분수(Cmax,mg/g)、약물체봉시간(Tmax,h)、청제솔(Ke/h)、흡수반쇠기(t1/2)화약시곡선하면적[AUC0-∞,mg/(g·h)]. 결과 GB재1~ 32 mg/L시선성관계량호,선성회귀방정위Y=0.0732X+0.056(r=0.992).GB-SMEDDS조화GB혼현액조대서관위후유착상사적약시곡선,단시제료급약후15 min시망막중적약물질량분수량자일치외,기타각개시간점GB-SMEDDS조시망막내약물질량분수균고우GB혼현액조.량조대서시망막중Cmax분별위(15.83±1.84) mg/g화(2.65±0.10) mg/g,AUC0-∞분별위(15.30±0.11)mg/(g·h)화(6.42±0.19)mg/(g·h). 결론 HPLC-ESI-MS구유쾌속、준학、령민도고적특점,괄합GB제제재SD대서시망막중약대동역학적연구.SMEDDS가이현저제고GB재시망막중적함량,가능제고기생물이용도.
Background Ginkgolide B (GB) has been proved to have neuroprotective and anti-apoptotic effects and can effectively inhibit apoptosis of retinal photoreceptor cells.But the high hydrophobic feature and low bioavailability of GB limit its clinical application.Self microemulsifying drug delivery system (SMEDDS) can effectively improve the infusibility drug dissolution and bioavailability in the retina.Objective This study was to investigate the pharmacokinetics and drug-time change of GB-loaded SMEDDS in retina.Methods Eighty SD rats were randomized into 2 groups,2.5% GB(40 mg/kg) of SMEDDS or GB suspension(0.1% DMSO dissolve) were gastrically given respectively in two groups.The rats were sacrificed and retinas were isolated 15,30,45 minutes and 1 hour,2,4,8,12 hours to prepare the retinal suspension.The content of GB in retina was assayed with high performance liquid chromatography-electrospray ionization-(1) (1)ss spectrum (HPLC-ESI-MS) and contrasted with standard curve.Practical drug dynamics program 3p87 was used to detect the pharmacokinetics parameters.The maximal content(Cmax,mg/g),time to peak (Tmax,h),clearance ratio (Ke/h),high-life period (t1/2) and area under the concentration-time curve(AUC0-∞,mg/(g · h)) of GB in various time points in retina after a single oral dose were calculated and compared between two groups.Results The standard curve was obtained over the concentration range of 1-32 mg/L with a linear regression equation,Y =0.0732X + 0.056 (r =0.992).A similar content-time curve was seen between GB suspension group and GB-SMEDDS group.The GB content was higher in GB-SMEDDS group than that in GB suspension group from 30 minutes through 12 hours after administration of drugs.The Cmax of GB-SMEDDS group and GB suspension group were(15.83±1.84) mg/g and(2.65±0.10) mg/g,the AUC0-∞ were(15.30±0.11)mg/(g· h)and(6.42±0.19)mg/(g · h).Conclusions HPLC-ESI-MS is proved to be a rapid,accurate,sensitive and suitable method for pharmocokinetic study of GB.SMEDDS can raise the concent of GB in retina,and it probably improve the bioavailability of GB.