当归多糖铁胃内滞留缓释片的制备及其犬体内药动学

目的:制备当归多糖铁胃内滞留缓释片(APIC-FSRT),考察其体外释放度,漂浮性能及制剂在犬体内的药动学。方法:以丙烯酸树脂Ⅱ、羟丙基甲基纤维素、聚维酮等为辅料,全粉末直接压片,制备了日给药2次的当归多糖铁缓释片,考察其在人工胃液中的漂浮性,以及在0.1mol.L-1盐酸溶液中的释放度。建立火焰原子吸收光谱法测定血清中药物浓度,采用DAS2.0统计软件估算Beagle犬服用对照组(力蜚能组)和受试试剂后的各个药动学参数,进行统计学分析。结果:所得胃滞留缓释片累积释放百分率符合Higuchi方程。在犬体内药动学参数为AUC0-t=6.0±1.0,MRT=7.4±0.5,Cmax=1.026±0.332,缓释片与力蜚能组比较,相对生物利用度为134%。结论:当归多糖铁胃内滞留缓释片制备工艺简单,缓释效果明显,与受试制剂比有显著差异。     

盐酸坦洛新肠溶缓释微丸的制备及其体内外评价

目的:制备盐酸坦洛新肠溶缓释微丸,并与参比制剂进行体内外一致性评价。方法:分别以乙基纤维素和羟丙甲纤维素为缓释包衣材料,以聚丙烯酸树脂为肠溶性包衣材料,采用流化床底喷包衣技术对载药微丸包衣,制备肠溶缓释微丸;考察释放度主要影响因素;采用多条释放曲线对比考察受试制剂与参比制剂体外一致性;双周期交叉试验设计,考察Beagle犬口服单剂量受试制剂与参比制剂后血浆中的药物浓度,评价受试制剂与参比制剂的体内一致性;考察受试制剂的体内外相关性。结果:确定了影响盐酸坦洛新释放的主要处方工艺因素;多条释放曲线测定结果表明,所制备的微丸与参比制剂体外一致性较好;Beagle犬体内药动学研究结果表明,受试制剂与参比制剂生物等效且体内外相关性良好。结论:成功制备了盐酸坦洛新肠溶缓释微丸,且与参比制剂体内外一致性良好。     

三七总皂苷缓释片的释放性能及体内外相关性研究

目的评价三七总皂苷缓释片的体外释放特性、体内药物动力学及体内外相关性。方法以磷酸盐缓冲液为释放介质,考察三七总皂苷缓释片的体外释放特性。以6只Beagle犬为实验动物,测定口服给予缓释片后血药浓度的变化,计算药代动力学参数,并对体外累积释放度和体内累积吸收百分率进行回归,考察其体内外相关性。结果三七总皂苷缓释片体外药物释放具有明显的缓释特性;与普通片相比,在Beagle犬体内的达峰时间延长,峰浓度降低,平均滞留时间延长,也具有明显的缓释特性。结论制得的三七总皂苷缓释片达到了缓慢释放药物的目的,并且其体内外参数间有明显的相关性。     

当归多糖铁胃内滞留缓释片在犬体内的药物动力学研究

目的:制备当归多糖铁胃内滞留缓释片(APIC-FSRT),考察其在犬体内的药物动力学。方法:以丙烯酸树脂Ⅱ、羟丙基甲基纤维素、聚维酮等为辅料,全粉末直接压片,制备了1 d给药2次的当归多糖铁缓释片,建立火焰原子吸收光谱法测定血清中药物浓度,采用DAS 2.0统计软件估算Beagle犬服用对照组(力蜚能组)和受试试剂后的各个药动学参数,进行统计学分析。结果:所得胃滞留缓释片在犬体内药动学参数为AUC(0-t)(6.024±0.950)mg.h.L-1,MRT(7.395±0.530)h,Cmax(1.026±0.332)mg.L-1,缓释片与力蜚能组比较,相对生物利用度为:134%。结论:当归多糖铁胃内滞留缓释片制备工艺简单,缓释效果明显,与受试制剂比有显著差异。     

洛伐他汀缓释片的体外释放度和生物利用度

目的:考察洛伐他汀缓释片的体内外性质,评价其缓释性能.方法:测定制剂的体外释放度,考察不同因素的影响;测定制剂在比格犬体内的血药浓度,以洛伐他汀胶囊为参比制剂,计算相对生物利用度等药动学参数.结果:制剂在pH 7.0的十二烷基硫酸钠溶液中可持续释药24 h,释放规律符合零级动力学和Higuchi方程,不同的压片压力、转篮转速对药物释放有明显影响.缓释片的相对生物利用度为(111.5±16.9)%.结论:缓释片与参比制剂在吸收程度方面具有生物等效性,在吸收速度方面差异有显著性,具有良好的缓释性能.     

基于粉末直接压片工艺的硝苯地平缓释片：制备、体外释放度及比格犬体内药动学评价

目的选用粉末直接压片工艺,以羟丙基甲基纤雏素为骨架材料制备日服1次的硝苯地平缓释片。方法建立24h的释放度测定方法并进行硝苯地平缓释片的体外评价;应用液相色谱-质谱联用技术研究缓释片在比格犬体内药代动力学,与市售参比制剂对比并计算相对生物利用度。结果受试制剂和参比制剂有相似的药代动力学参数,相对生物利用度为（100．9±12．4）％;药物体外累积释放百分数与体内吸收百分数有较好的相关性,r=0．9625。结论本工艺制得的硝苯地平缓释片可以达到缓释24h的要求。     

盐酸左氧氟沙星缓释片的体外释放度及其在犬体内的药动学

目的:研制盐酸左氧氟沙星缓释片的体外释放度和在Beagle犬体内的药动学。方法:采用紫外分光光度法测定盐酸左氧氟沙星的体外释放度。6条Beagle犬随机交叉口服单剂量300 mg盐酸左氧氟沙星缓释片(受试制剂)和盐酸左氧氟沙星片(参比制剂),采用高效液相色谱紫外检测法测定盐酸左氧氟沙星的血浆浓度,并采用BAPP 2.0程序计算药动学参数。结果:盐酸左氧氟沙星缓释片体外释放符合Higuchi方程。与参比制剂比较,受试制剂的AUC等效[(223.58±8.22)vs.(202.30±11.56)mg.h.L-1,P>0.05],峰浓度降低[(13.84±0.86)vs.(20.33±1.87)mg.L-1,P<0.05],达峰时间延长[(7.0±1.6)vs.(1.2±0.4)h,P<0.05]。结论:本实验制备的盐酸左氧氟沙星缓释片具有明显的体内外缓释效果。     

三七总皂苷肠溶微囊的药代动力学及体内外相关性

目的:考察三七总皂苷(panax notoginseng saponins,PNS)肠溶微囊在Beagle犬体内的释药行为及其体内外相关性研究。方法:采用双周期交叉试验设计,6只健康Beagle犬口服市售血栓通胶囊或自制PNS肠溶微囊(胶囊型)后,用HPLC法测定血药浓度,计算两制剂的药代动力学参数,进行生物利用度比较,并对体外累积释放度和体内累积吸收百分率进行线性回归。结果:自制PNS肠溶微囊对市售血栓通胶囊的相对生物利用度为三七皂苷R1(R1)313.63%,人参皂苷Rb1(Rb1)314.35%,人参皂苷Rg1(Rg1)202.03%,上述3成分在体内的平均滞留时间均延长,R1,Rb1和Rg1的体内外相关系数分别为0.866 4,0.958 0和0.719 2。结论:自制PNS肠溶微囊与市售血栓通胶囊相比生物利用度更高,Rb1体内外相关性较好,可用一定的体外释放条件进行体内行为的预测,R1和Rg1体内外相关性较差。     

枸橼酸莫沙必利胃内滞留缓释片的研制

目的研制以羟丙甲基纤维素（HPMC）为凝胶骨架材料的枸橼酸莫沙必利胃内滞留型缓释片,并考察体外释放度和漂浮性。方法以HPMC为缓释骨架,十八醇为助漂剂,碳酸氢钠为发泡剂,乳糖为填充剂,湿法制粒压片。结果最佳处方8h体外累积释药达到完全,起漂时间快。结论该法制备的胃内滞留型缓释片具有起漂快,漂浮时间长,缓释效果好,制备工艺简单等优点。     

磷酸苯丙哌林缓释胶囊的制备及生物等效性研究

目的 制备磷酸苯丙哌林缓释胶囊,并考察与磷酸苯丙哌林缓释片的生物等效性.方法 采用熔融法固体分散技术和滴丸工艺,制备磷酸苯丙哌林缓释胶囊;用RP-HPLC法测定Beagle犬单次和多次口服磷酸苯丙哌林缓释胶囊和参比制剂的血药浓度,并进行生物等效性评价.结果 磷酸苯丙哌林两种制剂的体外释放基本一致,在Beagle犬体内均具缓释特征.结论 磷酸苯丙哌林缓释胶囊具有缓释特征,与缓释片等效.     

The effects of vitamin A on cells of innate immunity in vitro

Retinoid treatment is suggested to promote development of inflammatory bowel disease, although preclinical studies are not supportive. We evaluated the effect of retinoids on cytokine response in in vitro-differentiated human dendritic cells (ivDCs) and macrophages (ivMACs) derived from healthy human donors and in cultured human THP-1 cells. Effect on human intestinal epithelial cell integrity was also assessed. Each cell type was incubated (±lipopolysaccharide [LPS]) with all-trans retinoic acid (ATRA), 13-cis-RA (isotretinoin) and 4-oxo-13-cis-RA. Cytokine analysis was performed by array analysis. Cultured human endothelial colorectal adenocarcinoma (Caco-2) cells were incubated with these retinoids and media analyzed for leakage by spectrofluorometric analysis. ATRA consistently and significantly inhibited LPS-induced release of the pro-inflammatory cytokines tumor necrosis factor, interleukin (IL)-6, macrophage inflammatory protein (MIP)-1α and MIP-1β. All retinoids tested stimulated release of the anti-inflammatory cytokines granulocyte–macrophage colony-stimulating factor and IL-10, and also monocyte chemotactic protein-1, vascular endothelial growth factor and eotaxin-1. Incubation with retinoids did not significantly alter the permeability of Caco-2 monolayers. Pre-treatment of each cell type with retinoids promoted an anti-inflammatory cytokine profile with only minimal effect on intestinal epithelial cell permeability; consistent with in vivo studies.     

盐酸氨溴索缓释片体内外相关性研究

目的考察盐酸氨溴索缓释片体外释放度与体内吸收的相关性。方法应用释放度测定法研究盐酸氨溴索缓释片体外释药行为 ,采用HPLC法测定盐酸氨溴索缓释制剂在家犬体内的血药浓度 ,按照Wagner Nelson公式计算药物的吸收分数。 结果 3种自制盐酸氨溴索缓释片与参比制剂生物等效 ,以药物累积吸收百分数 f(t)与相应时刻的体外累积释放百分数F(t)建立的一元线性回归方程 ,参比制剂与 3种自制制剂的体内外相关系数分别为 0 969、0 979、0 970和 0 983。结论盐酸氨溴索缓释片的体外释放度与体内吸收具有显著的相关性。     

In Vitro-In Vivo Relationship of Oral Extended-Release Dosage Forms

Purpose. A method to establish the in vitro-in vivo relationship of oral extended-release products is proposed. Methods. The approach utilizes incremental amounts of drug released and absorbed within defined time intervals, to construct a ² distributed variable for testing in vitro-in vivo similarity. Results. A case study is used to demonstrate that the similarities between incremental values of in vivo absorbed and in vitro dissolved fractions are distinguishable for different dissolution profiles despite naturally significant linear correlations between cumulative in vivo absorbed and in vitro dissolved fractions (with different dissolution tests) of an oral extended-release product. Conclusions. The method enables investigators to compare different in vitro dissolution profiles of an oral extended-release product to find an optimized dissolution profile to be the surrogate of the in vivo release process of the product.     

The action of small doses of lead on erythrocyte D-aminolevulinic acid dehydratase in the mouse

After a single intraperitoneal administration of lead in very small doses [1–100 g Pbac/kg body weight (bw)], there was a dose-dependent, highly significant inhibition of erythrocyte D-aminolevulinic acid dehydratase (D-ALA-D) activity in mice. The maximal inhibition occurred between 3 and 24 h post injection (p.i.). After that, a rapid recovery of the D-ALA-D activity took place so that four days after lead administration, enzyme activity exceeded even the normal value. Only after eight days p.i. did the D-ALA-D value return to the initial level after a biphasic course.After 10 i.p. injections of 0.1 to 10 g Pbac/kg bw, there was again a dose-dependent, highly significant inhibition of the erythrocyte D-ALA-D activity in mice. The maximal inhibition was shown to be 24 h after the last lead injection. In contrast to the single i.p. administration, however, we found a monophasic course for the return of D-ALA-D activity. The D-ALA-D values did not exceed the normal range at any time after 10 i.p. lead injections. Ten and 30 days oral administration of lead corresponding to i.p. doses exhibited similar results in D-ALA-D inhibition.     

Venoconstrictor responses to ergosine and ergosinine: Evidence for the isomerization of ergosinine

Ergosine and its D-isolysergic acid derivative ergosinine were investigated on canine saphenous veins both in vivo and in vitro. Following local i.v. infusion in vivo, about 5 times higher doses of ergosinine were necessary to produce the same venoconstrictor response as induced by ergosine. When administered orally, however, both ergot alkaloids were equi-effective. In vitro methiothepin, a 5-HT receptor blocker with high affinity for 5-HT₁ receptors, antagonized venoconstrictor responses to 5-HT and ergosine within the same concentration range, being significantly less potent when tested against norepinephrine. The reverse was true for the α₂-selective adrenoceptor blocker yohimbine, which was significantly more potent against norepinephrine and ergosine than against 5-HT, suggesting that ergosine has affinity to both 5-HT₁-like receptors and α₂-adrenoceptors. Concentration-response curves to norepinephrine were shifted to the right in a parallel fashion when ergosine or ergosinine were present in the organ baths, suggesting competitive antagonism. The blocking potency of ergosinine increased with increasing incubation times in Krebs-Henseleit solution becoming similar to that of ergosine when an incubation time of 2 hr was applied. It is suggested that the pharmacological activity of ergosinine is the consequence of an isomerization into its natural stereoisomer ergosine, which may occur both in vivo and in vitro.     

黄芩苷化合物现代常用测定方法的分析比较

黄芩的主要有效成分黄芩苷具有抗菌消炎、解热镇痛、抗病毒、抗肿瘤、降压及利尿等作用。黄芩苷是许多复方中药制剂的主要成分,而中药成分复杂,对分析技术也有特定的要求。本文对黄芩苷测定技术分光光度法、色谱法、红外光谱分析法等进行了综述。     

氟罗沙星的体内外试验相关性研究

本文研究了新型喹诺酮类药物氟罗沙星体外溶出与体内吸收之间的相关性。实验表明，本品口服吸收在血清中达峰时间较快，作用持久，消除半衰期为９．６０ｈｒ。在人工胃液中溶出速率较快，在血清达峰之前，体内吸收与体外溶出量之间呈现良好的相关性。     

双嘧达莫胃内漂浮片的研制

双嘧达莫 ( dipyridamole,1 )可抑制血小板聚集 ,有抗血栓形成作用 ,临床上多用于血栓栓塞性疾病 ,也可用于缺血性心脏病。 1生物半衰期短 ,血浆t1/ 2 仅为 2～ 3h,每天需用药 3～ 4次 [1,2 ] ,加上此类患者一般需长期服药 ,故宜制成缓释制剂。考虑到 1主要在胃内吸收 ,若将其制成胃内漂浮片 ,延长其在胃内的停留时间 ,可达到使血药浓度波动性减小、降低毒副作用以及便于患者使用的目的。1　试药与仪器聚丙烯酸树脂 (批号 2 0 0 110 6 2 8- 2 )、聚丙烯酸树脂 (批号 2 0 0 0 32 71)均由连云港云升实业公司提供 ;羟丙甲纤维素 (HPMC,湖州…     

制剂体内外相关性研究进展

综述体内外相关性（IVIVC）研究模型的建立、实验方法与步骤以及发展策略的最新研究进展.并指出目前IVIVC研究的局限性和体外实验的新方法.IVIVC研究中不存在通用的体外模型,因此IVIVC研究只能进行逐例建模.综合药物理化性质、生物药剂学特征、剂型设计和它们与消化道的相互作用对IVIVC研究十分重要.