Expedient synthesis of (S)- and (R)-norcoclaurine from (S)- and (R)-norarmepavine [corrected] prepared by the 1-phenylethylurea method

(+/-)-Norarmepavine [3] [corrected] prepared by Bischler-Napieralski synthesis afforded, on reaction with (S)-(-)-1-phenylethylisocyanate, ureas 4 and 5 which were separated and purified by crystallization from EtOH and 70% HOAc. Alcoholysis of 4 and 5 with sodium butoxide in n-BuOH afforded (S)-norarmepavine [3a] and (R)-norarmepavine [3b] [corrected], respectively. Hplc analysis of ureas prepared from 3a and 3b with (S)-(-)-1-phenylethylisocyanate showed them to be optically pure alkaloids. Refluxing 3a and 3b with 48% HBr afforded the hydrobromide salts of (S)-norcoclaurine [1a] and its (R)-isomer 1b, respectively.     

Involvement of calcium in the cardiac depressant actions of a garlic dialysate

In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca²⁺]_o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10⁻⁹ to 10⁻⁷ M), verapamil (10⁻⁹ to 10⁻⁷ M) and diltiazem (10⁻⁹ to 10⁻⁷ M) induced a concentration-depe synergism of the log concentration-effect curve of garlic dialysate on left atria. Verapamil and diltiazem (10⁻⁷ M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 × 10⁻¹⁰ to 1.1 × 10⁻⁶ M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca²⁺]_o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.     

The source of ca2+ for the spasmolytic actions of longicaudatine,a bisindole alkaloid isolated from Strychnos trinervis (Vell.) Mart. (Loganiaceae)

Longicaudatine, a tertiary bisindole alkaloid isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), antagonized in a noncompetitive manner, carbachol and histamine induced contractions of the guinea-pig ileum and bradykinin responses in the rat uterus. The respective pD₂' values (mean ± SE) were 4.61 ± 0.21, 4.98 ± 0.04 and 4.49 ± 0.01. Longicaudatine, unlike verapamil, had no effect on voltage dependent Ca²⁺ channels, as it failed to inhibit KCI or CaCl₂ induced contractions of guinea-pig ileum and depolarized rat uterus respectively. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, longicaudatine produced a slower and weaker inhibition of noradrenaline induced sustained contractions of rabbit aortic strips. However, in the aorta, the alkaloid antagonized the intracellular calcium dependent transient contractions of noradrenaline and longicaudatine (IC₅₀, 5.01 × 10^?7 M) was approximately 133 times more potent that procaine (IC₅₀, 6.68 × 10^?5 M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Longicaudatine may exert nonspecific spasmolytic effects by acting on intracellular Ca²⁺ stores, rather than on depolarization dependent or receptor operated Ca²⁺ channels.     

The interactions of paeoniflorin and veratrine on isolated rat atria

In this study, we attemped to identify the interactions and mechanisms between veratrine and paeoniflorin on isolated rat atria. Paeoniflorin alone showed no effect on the rat atria. Veratrine increased the atrial contraction and induced arrhythmia at 1×10⁻⁵ g/ml. Veratrine could directly induce contraction and elicit tetanic contraction at 1×10⁻⁴ g/ml in the left atria with or without electric stimulation. Paeoniflorin (4.8×10⁻⁶ to 4.8×10⁻³ g/ml), verapamil (2.2×10⁻⁶ g/ml), tetrodotoxin (TTX) (3.2×10⁻⁸ g/ml) and quinidine (7.5×10⁻⁶ g/ml) inhibited the increase of contraction and delayed the onset of contraction induced by veratrine (1×10⁻⁵ g/ml). The inhibitory effect of paeoniflorin combined with verapamil on the contraction induced by veratrine was more potent than that of paeoniflorin or verapamil alone. However, the inhibitory effect of paeoniflorin was not potentiated by TTX or quinidine. From the above results, the contraction evoked by veratrine in the rat atria may be concluded to be caused by the stimulation of Na⁺- and Ca²⁺-ion channels. The inhibition of paeoniflorin on the contraction induced by veratrine may primarily be related to the blockade of Ca²⁺ channels.     

Effects of crinum glaucum aqueous extract on intestinal smooth muscle activity

Crinum glaucum aqueous extract (1–8 mg/mL) produced a concentration dependent, non-competitive inhibition of contractions induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and calcium chloride (CaCl₂, 0.05–2 mM ) on the rat duodenum. Contractions of the guinea-pig ileum induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and histamine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) were inhibited by the extract (1–4 mg/mL). The extract (0.125–2.0 mg/mL) also, produced a concentration dependent relaxation of the guinea-pig taenia coli, precontracted with potassium chloride (40 mM ). It is concluded that the extract is a non-specific relaxant of the gastrointestinal smooth muscles used. © 1998 John Wiley & Sons, Ltd.     

Bisnordihydrotoxiferine and vellosimine from Strychnos divaricans root: Spasmolytic properties of bisnordihydrotoxiferine

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea-pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca²⁺ channels. For example in guinea-pig ileum, bisnordihydrotoxiferine (pD'₂ 3.92±0.09) and verapamil (pD'₂ 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'₂ 4.37±0.02) and verapamil (pD'₂ 6.83±0.10) also antagonized CaCl₂ induced contractions of K⁺-depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC₅₀, 6.10 × 10^?6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC₅₀, 2.30 × 10^?5M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.     

隔山香正丁醇部位对大鼠胸主动脉的舒张作用及机制的影响

目的:研究隔山香(Lemonfragrant Angelica Root,LAR)正丁醇部位对大鼠胸主动脉环的舒张作用,并探讨其可能的作用机制。方法:采用离体大鼠胸主动脉血管环灌流方法,考察0.34,0.65,1.22 g·L-1隔山香正丁醇部位对氯化钾(KCl)和去甲肾上腺素(norepinephrine,NE)预收缩的血管环张力的影响。在无Ca2+Kreb’s液中,考察0.34,0.65,1.22 g·L-1隔山香正丁醇部位对氯化钙(Ca Cl2)量效曲线的影响和NE预收缩的血管环张力的影响。激光共聚焦扫描显微镜检测平滑肌细胞内[Ca2+]i的变化。结果:隔山香正丁醇部位对KCl和NE预收缩的内皮完整和去除内皮血管环均具有浓度依赖性的舒张作用(P0.01),并且去除内皮后的舒张作用未受影响;无Ca2+条件下,隔山香正丁醇部位能使Ca Cl2,NE预收缩强度显著性降低(P0.01)。激光共聚焦扫描显微镜下,隔山香正丁醇部位(1.22 g·L-1)能抑制KCl,NE和毒胡萝卜素(thapsigargin,TG)引起的平滑肌细胞内[Ca2+]i升高。结论:隔山香正丁醇部位对大鼠胸主动脉血管有一定的舒张作用,可能通过抑制外钙内流和内钙释放发挥作用。本实验为隔山香水蒸气蒸馏后煎煮入药的成药制备工艺和水溶性药效指标成分的分离提供了依据。     

Herbal medicine Catuama induces endothelium-dependent and -independent vasorelaxant action on isolated vessels from rats,guinea-pigs and rabbits

The present study was designed to examine the vasorelaxant action of the herbal medicine Catuama and the hydroalcoholic extracts (HE) of each plant present in this product and to compare their effects with that caused by acetylcholine (ACh) in intact (⁺E) or in endothelium-rubbed (⁻E) rings of rat thoracic aorta (RA), guinea-pig pulmonary artery (GPPA), guinea-pig mesenteric artery (GPMA), rabbit pulmonary artery (RPA), rabbit mesenteric artery (RMA) precontracted with noradrenaline (NA) or phenylephrine (PE). The extract of Catuama (1-3000 μg/mL) produced graded relaxation of RA, ⁺E or ⁻E, with mean EC₅₀ of 430 μg/mL and ≊ 3000 μg/mL and E_max of 81 % ± 15 % and 47% ± 4 %, respectively. The nitric oxide (NO) synthase inhibitor, N^ω-nitro-L -arginine (L -NOARG, 100 μM ), inhibited in vasorelaxant action (p < 0.05) in RA (⁺E), while indomethacin (3 μM ), propranolol (1 μM ), glibenclamide (1 μM ), methylene blue (10 μM ) and apamin (0.1 μM ) had no significant effect. ACh (1-1000 μM ) caused graded relaxation in RA with ⁺E, these effects being markedly antagonized by L -NOARG (100 μM ), methylene blue (10 μM ) and partially by apamin (0.1 μM ), but not by indomethacin (3 μM ), glibenclamide (1 μM ) or propranolol (1 μM ). The Catuama extract (1-3000 μg/mL) produces partial relaxations in rings of RMA (mean EC₅₀ of 1073 μg7/ml and E_max of 56 % ± 13 %), an effect which was antagonized by L -NOARG (100 μM ). In RPA (⁺E) the extract produces partial relaxation followed by contraction (E_max 28 % ± 6 %), an effect which was abolished by L -NOARG (100 μM ) or methylene blue (10 μM ). The extract caused graded relaxation in rings of GPPA and GPMA with mean EC₅₀ values of 60 μg/mL and 1148 μg/mL and E_max 96% ± 2% and 88% ± 12%, respectively. L -NOARG (100 μM ) blocked the Catuama extract vasorelaxation in GPPA and only partially in GPMA, but markedly antagonized the vasorelaxations caused by ACh in both GPPA andRMA. The HE Paullinea cupana, Zinziber officinalis and Trichilia catigua (1-3000 μg/mL) caused a graded vasorelaxant effect ⁺E of RA with a mean EC₅₀ of 22, 55 and 1793 μg/mL and E_max 100%, 86% ± 7% 70% ± 2%, respectively. In addition the HE of P. cupana also caused graded relaxation in ⁻E of RA with EC₅₀ and E_max of 233 μg/mL and 100%, respectively, while T. catigua and Z. officinalis produced partial relaxation in RA ⁺E. In contrast the HE of Ptychopetalum olacoides caused little contraction (46% ± 14%). These results demonstrate that the medicinal herb Catuama produces significant vasorelaxation responses in vessels from different animal species, and show that its effects are in great part dependent on the release of NO or NO-derived substances. Our results also demonstrate that the vasorelaxant action of the product Catuama seems to be due to the action of the active principles present mainly in P. cupana; T. catigua and, to a lesser extent, in Z. officinalis. Such results may contribute to the explanation of its beneficial effect of Catuama herbal medicine in the management of cardiovascular disturbances. © 1997 John Wiley & Sons, Ltd.     

Mechanisms of Vasorelaxation Induced by Hexahydrocurcuminin Isolated Rat Thoracic Aorta

This study was designed to examine the vasorelaxant effects of hexahydrocurcumin (HHC), one of the major natural metabolites of curcumin from Curcuma longa, on rat isolated aortic rings, and the underlying mechanisms. Isometric tension of the aortic rings was recorded using organ bath system. HHC (1 nM to 1 mM) relaxed the endothelium‐intact aortic rings pre‐contracted with PE and KCl in a concentration‐dependent manner. Removal of the endothelium did not alter the effect of HHC‐induced relaxation. In Ca²⁺‐free Krebs solution, HHC significantly inhibited the CaCl₂‐induced contraction in high K⁺ depolarized rings and suppressed the transient contraction induced by PE and caffeine in a concentration‐dependent manner. HHC was also observed to relax phobal‐12‐myristate‐13‐acetate (PMA), an activator of protein kinase C (PKC), precontracted aortic rings in a concentration‐dependent manner with EC₅₀ values equivalent to 93.36 ± 1.03 μM. In addition, pre‐incubation with propranolol (a β‐adrenergic receptor blocker) significantly attenuated the HHC‐induced vasorelaxation. These results suggest that the vasorelaxant effect of HHC is mediated by the endothelium‐independent pathway, probably because of the inhibition of extracellular Ca²⁺ influx through voltage‐operated Ca²⁺ channels and receptor‐operated Ca²⁺ channels, the inhibition of Ca²⁺mobilization from intracellular stores, as well as inhibition of PKC‐mediated Ca²⁺‐independent contraction. Moreover, HHC produces vasorelaxant effects probably by stimulating the β‐adrenergic receptor. Copyright © 2015 John Wiley & Sons, Ltd.     

Spasmolytic actions of warifteine,a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl. (menispermaceae)

Warifteine, a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl., produced a reversible, nonspecific and noncompetitive antagonism of histamine, carbachol and bradykinin induced contractions of the guinea-pig ileum. The corresponding pD'₂ values (mean±SE) were 4.90±0.15, 4.95±0.20 and 5.03±0.11. Warifteine also antagonized oxytocin and bradykinin induced contractions of the rat uterus in a similar manner with pD'₂ values of 4.30±0.26 and 3.76±0.06 respectively. In the guinea-pig trachea, the alkaloid inhibited spontaneous tone (IC₅₀, 1.1 × 10^?5M) as well as carbachol induced sustained contractions (IC₅₀, 2.9 × 10^?5M). As warifteine antagonized KCI induced contractions of the guinea-pig ileum (pD'₂ value 4.57±0.10), inhibition of Ca⁺⁺ influx through voltage operated Ca⁺⁺ channels may be partially responsible for its antispasmodic activity. However, the reported local anaesthetic property of warifteine may not contribute to the observed muscle relaxation as procaine failed to reduce the spontaneous tone or consistently antagonize carbachol induced contractions of the trachea and was inactive in inhibiting voltage operated Ca⁺⁺ channels in the ileum.     

草乌及其炮制品中6种生物碱类成分的含量测定

目的: 测定不同产地草乌及草乌炮制品中6种生物碱的含量,综合评价其安全性和有效性。 方法: 采用HPLC同时测定6种生物碱含量,比较草乌炮制前后有效成分含量变化。 结果: 草乌生品中单酯型生物碱含量0.408 1～1.718 2 mg·g^-1,双酯型生物碱含量0.660 4～8.653 2 mg·g^-1;炮制后双酯型生物碱大大减少,而单酯型生物碱则明显增加。 结论: 不同产地草乌中6种生物碱的含量差异较大,常压蒸、煮法具有一定科学性,炮制后双酯型生物碱<0.04%,而单酯型生物碱常超出限量要求。     

高效液相质谱联用研究伐昔洛韦人体生物等效性

 目的研究健康人po盐酸伐昔洛韦片后的药动学和生物等效性。方法20个健康受试者采用随机分组自身交叉对照试验设计,口服盐酸伐昔洛韦片600 mgHPLC-MS联用法测定血浆中代谢产物阿昔洛韦浓度,以BAPP程序计算其药动学参数和评价生物等效性。结果在选定的色谱/质谱条件下阿昔洛韦与内标及血浆杂质分离良好,在41.6～5.34×103μg·L^-1内线性良好。阿昔洛韦的相对回收率大于96.7%,日内和日间RSD小于10.2%。盐酸伐昔洛韦片受试制剂(T)和参比制剂(R)的主要药动学参数:t_max分别为(1.5±0.6)(T)和(1.5±0.6)h(R),ρ_max分别为(2.83×10³±7.76×10²)(T)和(2.72×10³±8.50×10²)μg·L^-1(R);t_1/2分别为(3.21±0.29)(T)和(3.23±0.30)h(R);AUC_0-14分别为(1.02×10⁴±2.03×10³)(T)和(9.91×10³±2.46×10³)μg·h·L^-1(R);盐酸伐昔洛韦片相对生物利用度为(104.5±14.0)%。结论用LC-MS测定血浆中代谢产物阿昔洛韦浓度,杂质无干扰,定量限低,重复性好,准确度高。受试的盐酸伐昔洛韦片与参比的盐酸伐昔洛韦片生物等效。     

小檗碱的油水分配系数及其在体肠循环灌流模型中的肠吸收特性

目的: 测定小檗碱和黄连总生物碱中小檗碱的油水分配系数,并研究小檗碱、黄连总生物碱和清热通腑片中小檗碱在大鼠空肠和回肠的吸收特性,同时比较两者的相关性。 方法: 采用摇瓶法测定小檗碱在正辛醇-水中的表观油水分配系数,采用大鼠在体肠循环灌流模型研究小檗碱的吸收特性,UPLC测定小檗碱质量浓度,计算小檗碱的油水分配系数、肠吸收速度常数(Ka)表观渗透系数(P_app)。 结果: 小檗碱和黄连总生物碱在肠液/正辛醇中油水分配系数分别为0.213 5,0.175 7。小檗碱在空肠中Ka=0.046 6,P_app=4.88×10^-6cm·s^-1,回肠中Ka=0.034 9,P_app=4.13×10^-6cm·s^-1;黄连总生物碱在空肠中Ka=0.035 1,P_app=3.92×10^-6cm·s^-1,回肠中Ka=0.026 6,P_app=3.21×10^-6cm·s^-1;清热通腑片在空肠中Ka=0.028 3,P_app=3.11×10^-6cm·s^-1,回肠中Ka=0.018 1,P_app=2.23×10^-6cm·s^-1。 结论: 小檗碱在空肠和回肠中均有吸收,且吸收速率较慢,但空肠吸收速率大于回肠,具有显著性差异;小檗碱的吸收快慢为小檗碱对照品>黄连生物碱物>清热通腑片,小檗碱油水分配系数的预测结果与肠吸收结果基本一致。     

芪葵缓释片中6种活性成分在兔血浆中的药动学研究

目的以芪葵颗粒为参照,比较芪葵缓释片中6种成分在兔血浆内的药动学行为差异。方法以地西泮作为内标建立兔血浆中黄芪甲苷、金丝桃苷、异槲皮苷、芦丁、莫诺苷、马钱苷的LC-MS/MS检测方法。考察兔ig给予芪葵缓释片及芪葵颗粒后不同时间的血药浓度变化,并计算6种成分的药动学参数。结果 6种有效成分线性回归方程分别为黄芪甲苷Y=1.0×10~(-4) X-0.009 9(r=0.999 7);莫诺苷Y=1.0×10~(-4) X+0.038 7(r=0.999 4)、马钱苷Y=3.0×10~(-5) X+0.008 7(r=0.999 3)、金丝桃苷Y=1.0×10~(-3) X-0.016 1(r=0.999 0)、芦丁Y=5.0×10~(-4) X-0.011 5(r=0.999 4)、异槲皮苷Y=1.7×10~(-3) X-0.307 5(r=0.999 2);日内、日间精密度和准确度以及提取回收率均符合要求。兔ig给予芪葵缓释片及芪葵颗粒后,芪葵颗粒中莫诺苷、马钱苷、黄芪甲苷、芦丁、金丝桃苷、异槲皮苷达峰浓度(C_(max))分别为(1.333±0.051)、(1.238±0.164)、(0.830±0.079)、(0.127±0.017)、(0.444±0.048)、(0.223±0.048)mg/L;t1/2分别为(3.848±0.311)、(3.822±0.757)、(4.982±1.140)、(3.730±0.298)、(4.732±0.642)、(5.132±0.901)h;AUC_(0～t)分别为(3.069±0.307)、(2.891±0.943)、(2.079±0.306)、(0.313±0.068)、(1.087±0.177)、(0.496±0.129)mg·h/L。芪葵缓释片中莫诺苷、马钱苷、黄芪甲苷、芦丁、金丝桃苷、异槲皮苷的C_(max)分别为(0.985±0.130)、(0.961±0.175)、(0.693±0.101)、(0.094±0.012)、(0.354±0.045)、(0.201±0.037)mg/L;t1/2分别为(4.691±0.337)、(5.62±1.640)、(6.408±0.707)、(4.103±0.341)、(6.048±0.882)、(5.803±0.590)h;AUC_(0～t)分别为(5.191±1.046)、(6.168±1.250)、(4.293±0.823)、(0.485±0.103)、(1.840±0.432)、(0.924±0.190)mg·h/L。芪葵缓释片与芪葵颗粒相比,莫诺苷、马钱苷、黄芪甲苷、芦丁、金丝桃苷、异槲皮苷相对生物利用度分别为169.1%、213.3%、206.5%、156.0%、169.3%、186.3%。结论芪葵缓释片能显著提高各有效成分的生物利用度。     

Inhibiting Activity of Some Glucoindolalkaloids and Iridoids from Sickingia williamsii on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examined the effects of the extracts (petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH), partially purified fractions and pure compounds (mainly alkaloids and iridoids) from Sickingia williamsii on the electrically induced contractions of the isolated guinea-pig ileum. The results of our experiments indicate that CHCl₃/MeOH (9:1) and CHCl₃ extracts, tested at concentrations of 300, 150 and 30 μg/mL, dose-dependently reduced the guinea-pig ileum electrical contractions, whereas MeOH and petroleum ether extracts did not affect it. Furthermore, both the partially purified fractions I–IV each tested at concentrations of 500, 250 and 100 μg/mL from the CHCl₃/MeOH (9:1) extract and some pure compounds (10⁻⁴ M , 5×10⁻⁵ M and 2.5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum. As the active pure compounds possess an indole nucleus or/and an iridoid nucleus in their structures, the inhibitory effects appear to depend on these structures.     

不同因子对长春花愈伤组织中药用成分积累的影响

 目的 研究继代次数、继代龄(继代组织块的年龄)、生长素、金属离子等因子的改变对长春花愈伤组织生长及吲哚生物碱类药用成分积累的影响。方法 测定不同因子的影响下,长春花愈伤组织的鲜重,并对吲哚总碱进行提取、含量测定和比较。结果 随继代次数的增加,长春花愈伤组织中吲哚总碱含量有所下降;20 d继代龄最利于组织生长;2,4-二氯苯氧乙酸的存在对吲哚总碱的积累有一定的抑制作用,但却有利于愈伤组织生长,两种生长素组合比单一的生长素更利于组织生长,也较利于吲哚总碱积累;钙离子浓度为220 mg·L^-1,锌离子浓度为8.6哗·L^-1时,对提高吲哚总碱产量最有效。结论 继代次数、继代龄、生长素、金属离子对长春花愈伤组织生长及吲哚生物碱类药用成分的积累有较大影响。     

姜黄素葡甲胺共晶的大鼠肠吸收特征研究

目的比较姜黄素葡甲胺共晶(MGC,姜黄素与葡甲胺通过氢键连接的新共晶化合物)与姜黄素的肠吸收参数变化。方法采用大鼠在体肠段单向灌流模型,用紫外分光光度法(UV)对药物的质量浓度进行检测,分别计算在大鼠各肠段的吸收速率常数(Ka)和表观渗透系数(Papp)。结果 MGC在十二指肠与结肠的Ka和Papp比较有明显差异(P0.05),其他各肠段间吸收特征相近(P0.05)。各肠段Ka数据排序:十二指肠空肠回肠结肠;Papp数据排序:十二指肠空肠结肠回肠,MGC的全肠段Ka为(9.966±0.030)×10-3 min-1,Papp为(6.871±0.013)×10-3 cm/min,较姜黄素分别提高了1.53和2.21倍。结论 MGC较姜黄素有更好的肠吸收特征,提示MGC生物利用度可能提高。     

苦瓜水提取物对高脂血症小鼠的降血脂作用研究

目的:探讨苦瓜水提取物对高脂血症模型小鼠的降血脂作用.方法:高脂饲养建立高脂血症小鼠模型,随机分成4组,即苦瓜水提取物高、低剂量组(30,10 g·kg-1)、左旋肉碱(1 g·kg-1)组、模型组,另取同步饲养的正常小鼠作为空白对照组,每组10只.连续灌胃给药4周后,眼眶后静脉丛取血,分离血清,检测血清总胆固醇(TC)、甘油三酯(TG)含量;计算肝脏指数,HE染色观察肝脏组织形态学改变.结果:与模型组比较,各给药组小鼠血清TC,TG含量和肝脏指数均明显降低(P ＜0.05,P＜0.01),其中苦瓜水提取物高剂量组小鼠血清TC,TG含量和肝脏指数,与模型组差异非常显著(P＜0.01);肝组织染色结果显示苦瓜水提取物能明显减少高脂血症小鼠肝脏的脂肪沉积.结论:苦瓜水提取物具有良好的降血脂作用.     

重组人组织型纤溶酶原激活剂缺失变体的溶栓作用及对血小板聚集和胞浆游离钙离子浓度的影响

 目的 研究重组人组织型纤溶酶原激活剂缺失变体(reteplase,Ret)的溶栓作用以及对离体家兔血小板聚集功能和对血小板静息状态胞浆内游离钙浓度的影响。方法 家兔血栓模型采用动-静脉旁路法,血小板聚集实验采用比浊法,血小板静息状态胞浆内游离钙浓度采用Fura-2荧光测定法。结果Ret(3.75×10⁵,7.50×10⁵,15.0×10⁵U·kg^-1)对家兔动-静脉旁路所形成的血栓有明显溶栓作用,可明显减轻血栓干湿重量,并呈一定的剂量依赖性。Ret(1 000,3 000,10 000 U·mL^-1)对ADP诱导的血小板聚集可产生浓度依赖性的抑制作用,并可明显降低血小板静息状态的[Ca²⁺]_i,并呈一定的浓度依赖性。结论Ret具有明显的血栓溶解作用,可明显抑制ADP诱导的血小板聚集,并明显降低血小板静息状态的[Ca²⁺]_i。     

复方法莫替丁咀嚼片临床药动学研究

 目的研究复方法莫替丁咀嚼片在正常人体内的药动学,据此拟定临床给药方案。方法采用HPLC测定12名健康志愿受试者单剂量空腹po(低、中、高剂量,即含法莫替丁20,30,40 mg)、进食后口服以及多剂量口服复方法莫替丁咀嚼片后,法莫替丁血药浓度变化情况。结果单剂量空腹po低、中、高3个剂量法莫替丁AUC_0→12分别是:(243.39±41.10),(347.05±25.95)和(516.12±55.37)μg·h·L^-1;达峰时间分别为:(2.96±0.33),(2.50±0.30)和(2.63±0.38)h;峰浓度分别是:(67.10±5.71),(94.18±3.21)和(125.43±5.30)μg·L^-1;消除速率常数分别为:(0.18±0.02),(0.17±0.02)和(0.19±0.04)h^-1;消除半衰期分别为:(3.85±0.52),(4.12±0.59)和(3.85±0.77)h。进食后服用低剂量的供试制剂,法莫替丁AUC_0→12为(257.94±39.88)μg·h·L^-1,达峰时间为(2.83±0.39)h,峰浓度为(64.56±2.18)μg·L^-1,消除速率常数为(0.20±0.04)h^-1,消除半衰期为(3.54±0.69)h。多剂量给予20 mg供试制剂达稳态后,法莫替丁AUC_0→τ为(310.02±23.95)μg·h·L^-1,达峰时间为(2.46±0.33)h,稳态谷浓度是(7.84±1.31)μg·L^-1,稳态峰浓度为(60.78±2.13)μg·L^-1,平均稳态血药浓度是(25.83±2.00)μg·L^-1,消除速率常数为(0.20±0.03)h^-1,消除半衰期为(3.61±0.54)h,波动度(DF)为2.06,蓄积因子为0.02。结论对空腹 po 3个剂量供试制剂的AUC_0→12/剂量进行q检验,结果表明,法莫替丁在体内符合线性动力学过程;对空腹与进食后给予供试制剂的有关药动学参数进行差别检验,结果表明,食物对法莫替丁的体内过程无显著影响;多剂量试验结果表明,法莫替丁在体内无蓄积作用。