酮基布洛芬-β-环糊精包合物的研究

研究了酮基布洛芬-β-环糊精包合物的制备工艺、理化特性和生物利用度。采用沉淀法、共沉淀法、固相包合法和冷冻法都能获得包合物。形成包合物后其溶解度、溶出度明显提高。前三种方法形成的包合物其生物利用度分别为酮基布洛芬原料的276,153和152%。固相包合法简便,含量稳定,适宜于工业生产。     

相溶解度法研究不同环糊精对美沙拉嗪的增溶作用

摘 要 目的： 考察β-环糊精（β-CD）及羟丙基 β-环糊精（HP-β-CD）对美沙拉嗪（MSZ）的增溶作用,为其包合物的制备提供理论依据。方法: 采用相溶解度法分别考察不同浓度和不同温度下β-CD及HP β-CD对MSZ的增溶作用,绘制出MSZ的相溶解度曲线,并计算包合常数K及包合动力学参数ΔG、ΔH及ΔS。结果: MSZ在两种环糊精中的相溶解度曲线均为AL型,随着温度的升高,两种环糊精对MSZ的包合常数K值均降低,当环糊精浓度和温度相同时,HP β-CD的增溶效果明显优于β-CD;包合动力学参数ΔG、ΔH及ΔS均为负值。结论:两种环糊精对MSZ均有较好的增溶作用,HP-β-CD的增溶效果优于β-CD。     

羟丙基-β-环糊精对吲达帕胺溶解度的影响

目的 考察不同pH条件下不同浓度的羟丙基-β-环糊精对吲达帕胺的增溶作用.方法 在室温下运用相溶解法对吲达帕胺的溶解性进行实验,采用紫外分光光度法测定吲达帕胺在缓冲液中的浓度,并对其稳定性进行评价;采用红外及差示扫描热量法对包合物的形成进行确证.结果 随羟丙基-β-环糊精浓度的增加和pH的增大,吲达帕胺的溶解度可提高.结论 一定条件下羟丙基-β-环糊精可增加吲达帕胺的溶解度.     

羟丙基-β-环糊精对降香挥发油溶解度及稳定性的影响

目的 考察羟丙基-β-环糊精(HP-β-CD)对降香挥发油的溶解度及稳定性的影响.方法 采用紫外分光光度法测定降香挥发油的含量;在不同温度及不同pH条件下进行相溶解度实验,计算包合平衡常数K;考察不同浓度的降香挥发油-HP-β-CD增溶溶液在高温、强光照射、100 ℃灭菌及低温放置条件下的稳定性.结果 降香挥发油在HP-β-CD溶液中的相溶解度曲线为AL型;温度升高,K值增大,但增溶倍数减小;pH增大,K值增大,但中性环境下增溶倍数最大;降香挥发油-HP-β-CD增溶溶液在100℃灭菌及高温条件下较不稳定,在强光照射及低温放置条件下均较稳定,且随着HP-β-CD的浓度增大,稳定作用越好.结论 HP-β-CD增大了降香挥发油的溶解度,提高了其在水中的稳定性.     

相溶解度法研究两种不同类型环糊精对吲达帕胺的包合作用

目的:研究两种不同类型环糊精羟丙基-β-环糊精(HP-β-CD)、γ-环糊精(γ-CD)对吲达帕胺的包合增溶作用,并进行包合物的鉴定.方法:运用相溶解度法考察不同类型环糊精对药物的增溶作用,并用差示扫描量热(DSC)法和红外光谱(IR)法对包合物进行鉴定.结果:确定了吲达帕胺与HP-β-CD和γ-CD包合物的相溶解度图,并计算了表观稳定常数,用DSC法和IR法确证2种不同类型环糊精的包合物均已形成.结论:2种不同类型环糊精对吲达帕胺都有显著的增溶作用,且都能形成包结比为1:1的包合物,γ-CD的增溶作用更强,形成的包合物更稳定.     

相溶解度法研究羟丙基-β-环糊精对淫羊藿苷的增溶作用

目的：利用相溶解度曲线法研究不同质量浓度的羟丙基-β-环糊精对淫羊藿苷溶解度的影响。方法配制一系列质量浓度的HP-β-CD溶液,加入过量的淫羊藿苷,绘制不同温度下的相溶解度图。结果相溶解度曲线为线性关系,包合模型为AL型,淫羊藿苷与HP-β-CD以1∶1的比例包合。在25,35和45℃时,其表观结合常数分别为52．01,64．66和41．42 L · mmol-1。结论 H P-β-CD对淫羊藿苷有一定的增溶作用。     

7α-和7β-甲基-10β,17β-二乙酰氧基-△4-雌甾烯-3酮的抗早孕作用

7α-和7β-甲基-10β,17β-二乙酰氧基-△⁴-雌甾烯-3酮(简称7α-和7β-甲-乙氧雌酮)对小鼠抗早孕ED₅₀分别为1.6和5.5 mg/kg。7α-甲-乙氧雌酮在大鼠也有抗早孕作用并使血浆孕酮浓度降低,应用10 μg/ml浓度能抑制离体妊娠大鼠卵巢孕酮合成。7α-和7β-甲-乙氧雌酮与兔子宫胞浆雌二醇受体的相对结合亲和力(RBA)分别为10.8和1.5,与孕酮受体的RBA均<1.7α-和7β-甲-乙氧雌酮都有较弱的雌激素和抗雌激素活性。     

羟丙甲纤维素和聚维酮对氯硝西泮与羟丙基-β-环糊精包合作用的影响

采用相溶解度法考察羟丙甲纤维素（HPMC）和聚维酮（PVP）对水溶液中氯硝西泮与羟丙基-β-环糊精（HP-β-CD）包合作用的影响。以UV法测定氯硝西泮在溶液中的浓度。无论水溶液中是否存在HP—β—CD，PVP均能增加氯硝西泮的溶解度（P〈0．01）：HPMC作用不明显。     

7α和7β-甲基-10β,17β-二乙酰氧基-4-雌甾烯-3-酮的合成

由于7α-甲基或10β-乙酰氧基4(5)烯-3-酮雌(雄)甾化合物具有显著的抗着床或抗蜕膜活性,我们合成了既具有7α-甲基或7β-甲基又具有10β-乙酰氧基的两个新甾族化合物(1_a)和(1_b)。经药理试验表明(1_a)和(1_b)对孕鼠均有抗早孕作用。     

铁刀木中一个新的色酮苷

目的 研究铁刀木的化学成分。方法 利用硅胶柱色谱和薄层色谱分离铁刀木的化学成分,通过理化常数测定和波谱分析等鉴定化合物的结构。结果从铁刀木树干中分离并鉴定了5个化合物,其结构分别鉴定为:β-谷甾醇(I),蔗糖(II),正二十八醇(III),2-甲基-5-(2′-羟丙基)-7-羟基色酮-2′-O-β-D-吡喃葡糖苷(IV),3,3′,4,5′-四羟基二苯乙烯(V)。结论化合物II,III,V为首次从该植物中分得,化合物IV为新化合物。     

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin

Introduction: Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin.

Areas covered: Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future.

Expert opinion: The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.     

Influence of polyvinylpyrrolidone quantity on the solubility,crystallinity and oral bioavailability of fenofibrate in solvent-evaporated microspheres

The objective of this study is to explore the influence of polyvinylpyrrolidone (PVP) quantity on the solubility, crystallinity and oral bioavailability of poorly water-soluble fenofibrate in solvent-evaporated microspheres. Numerous microspheres were prepared with fenofibrate, sodium lauryl sulphate (SLS) and PVP using the spray-drying technique. Their aqueous solubility, dissolution, physicochemical properties and pharmacokinetics in rats were assessed. The drug in the solvent-evaporated microspheres composed of fenofibrate, PVP and SLS at the weight ratio of 1:0.5:0.25 was not entirely changed to the amorphous form and partially in the microcrystalline state. However, the microspheres at the weight ratio of 1:4:0.25 provided the entire conversion to the amorphous form. The latter microspheres, with an improvement of about 115 000-fold in aqueous solubility and 5.6-fold improvement in oral bioavailability compared with the drug powder, gave higher aqueous solubility and oral bioavailability compared with the former. Thus, PVP quantity played an important role in these properties of fenofibrate in the solvent-evaporated microspheres.     

Microemulsions as drug delivery systems to improve the solubility and the bioavailability of poorly water-soluble drugs

Importance of the field: Microemulsions have been studied extensively as potential drug delivery vehicles for poorly water-soluble drugs. An understanding of the physicochemical and biopharmaceutical characteristics of the microemulsions according to administration routes will provide guidance for designing the formulations of microemulsions.

Areas covered in this review: In this paper, the use and the characteristics of microemulsions as drug delivery vehicles are reviewed. As the formulations of the microemulsion always include a great amount of surfactant and co-surfactant, which may cause hemolysis or histopathological alterations of the tissue, the potential toxicity or the irritancy of microemulsions is also discussed in this paper.

What the reader will gain: Developments of microemulsions for poorly water-soluble drugs in recent years are included in this review. Several factors limiting the commercial or clinical use of microemulsions are also discussed.

Take home message: Considering the potential in enhanced drug uptake/permeation and facing the limitations, their unique properties make microemulsions a promising vehicle for poorly water-soluble drugs.     

Medium optimization and potential hepatoprotective effect of mycelial polysaccharides from Pholiota dinghuensis Bi against carbon tetrachloride-induced acute liver injury in mice

Response surface methodology was employed to optimize the medium compositions for the production of mycelial polysaccharide from Pholiota dinghuensis Bi (PDP). As a result, the optimal medium for crude PDP production was determined as follows (g/L): glucose 36.0, corn flour 11.8, peptone 3.0, yeast extract 5.4, KH₂PO₄ 1.0, and MgSO₄ 1.5. In a verification experiment, a yield of 756 ± 38 mg/L crude PDP was obtained. Furthermore, biochemical assay and histopathological analysis showed that crude PDP exerted significant hepatoprotective effect in a dose-dependent manner against carbon tetrachloride (CCl₄)-induced acute liver injury. Crude PDP prevented the increase of activities of serum alanine aminotransferase and aspartate aminotransferase, reduced the formation of malondialdehyde and enhanced the activities of superoxide dismutase and glutathione peroxidase in CCl₄-induced hepatotoxicity in mice.     

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia-reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs.     

Sensitization of vanilloid receptor involves an increase in the phosphorylated form of the channel

A vanilloid receptor (VR1, now known as TRPV1) is an ion channel activated by vanilloids, including capsaicin (CAP) and resiniferatoxin (RTX), which are pungent ingredients of plants. Putative endogenous activators (anandamide and metabolites of arachidonic acid) are weak activators of VR1 compared to capsaicin and RTX, and the concentrations of the physiological condition of those activators are not sufficient to induce significant activation of VR1. One way to overcome the weak activation of endogenous activators would be the sensitization of VR1, with the phosphorylation of the channel being one possibility. The phosphorylation of VR1 by several kinases has been reported, mostly by indirect evidence. Here, using an in vivo phosphorylation method, the VR1 channel was shown to be sensitized by phosphorylation of the channel itself by multiple pathways involving PKA, PKC and acid. Also, in sensitizing VR1, BK appeared to show activation of PKC for the sensitization of VR1 by phosphorylation of the channel.     

灯盏花素及其β-环糊精包合物在大鼠体内的药代动力学

目的建立测定大鼠血浆中灯盏乙素浓度的反相高效液相色谱法，研究灯盏花素及其β-环糊精包合物(灯盏花素-β-CD)大鼠灌胃后体内药代动力学行为。方法以甲醇-水-醋酸盐缓冲液为流动相，Shim-pack C₁₈为固定相；12只大鼠随机均分为2组，分别灌胃灯盏花素及其包合物后，检测血浆药物浓度。药时数据采用3P97药代计算程序处理。结果线性范围10-400 ng·mL^-1，方法回收率95.32%-98.81%；灯盏花素和包合物的C_max分别为(154±18) ng·mL^-1和(328±31) ng·mL^-1；AUC_0-12h分别为(710±126) ng·h·mL^-1和(1 093±200)ng·h·mL^-1，经t检验两者有极显著性差异(P<0.01)。结论该法准确、灵敏，适用于灯盏乙素血浆浓度的测定；制备的灯盏花素包合物与灯盏花素相比吸收显著增加。     

Effect of antacids on aspirin dissolution and bioavailability

The in vitrodissolution profile, in vitroand in vivobuffering characteristics, and single-dose bioavailability of various buffered aspirin tablet formulations were studied. Buffering agents,such as magnesium and aluminum hydroxides (formulations B and C) or magnesium carbonate and aluminum glycinate (formulation D), significantly increased the rate of aspirin dissolution from solid dosage forms as compared to an unbuffered tablet (formulation A). The extent of aspirin absorption was equivalent with all formulations;however, the faster rate of dissolution (t₅₀ and t₉₀)with buffered formulations resulted in earlier and higher peak concentration of salicylate compared to that with unbuffered formulation, following a two-tablet dose in the fasting state. A comparison of the in vivobuffer capacity of a four-tablet dose of formulations B and D was performed in the postcibal state at the time of maximal meal-induced acid secretion, using a radiotelemetry procedure for determination of pH. Formulation B prolonged the interval of elevation of intragastric pH > 3 for 32 min as compared to 12 min for D.     

Evaluation of the genotoxic potential of single-wall carbon nanotubes by using a battery of in vitro and in vivo genotoxicity assays

The genotoxic potential of a high purity sample of single-wall carbon nanotubes (SWCNTs) was evaluated using a battery of in vitro and in vivo genotoxicity assays. These comprised a bacterial reverse mutation test (Ames test), an in vitro chromosomal aberration test, and an in vivo mouse bone marrow micronucleus test. The SWCNTs exerted no genotoxicity in Salmonella typhimurium TA97, TA98, TA100, and TA1535, or in Escherichia coli WP2 uvrA/pKM101, whether in the absence or presence of metabolic activation and at concentrations of 12.5–500 μg/plate. In the chromosomal aberration test, at 300–1000 μg/mL, the SWCNTs did not increase the number of structural or numerical chromosomal aberrations, whether the test was conducted with or without metabolic activation. In the in vivo bone marrow micronucleus test, doses of 60 mg/kg and 200 mg/kg SWCNTs did not affect the proportions of immature and total erythrocytes, nor did it increase the number of micronuclei in the immature erythrocytes of mice. The results of these studies show that the high purity and well-dispersed sample of SWCNTs are not genotoxic under the conditions of the in vitro bacterial reverse mutation assay, chromosomal aberration assay, or in vivo bone marrow micronucleus test, and thus appear not to pose a genotoxic risk to human health in vivo.     

新疆紫草提取物对小鼠急性酒精性肝损伤的保护作用

目的研究新疆紫草提取物(AE-Ⅰ、AE-Ⅱ)对小鼠急性酒精性肝损伤的保护作用。方法灌胃35度二锅头白酒16 ml/kg造酒精性肝损伤模型,观察肝脏、脾脏系数,血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、胆固醇(CHO)、甘油三酯(TG)、肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、一氧化氮(NO)的水平和肝脏病理组织学变化。结果AE-Ⅰ、Ⅱ各剂量组均可降低小鼠脾脏系数和血清ALT、TG活性,升高肝组织SOD、GSH-Px活性,并降低肝组织MDA和NO含量(P<0.05);而仅有AE-Ⅰ(0.8 g/kg)可以降低肝脏系数(P<0.05);AE-Ⅰ(0.8 g/kg)和AE-Ⅱ(2,4 g/kg)可降低小鼠血清AST活性(P<0.05);AE-Ⅰ(0.8 g/kg)和AE-Ⅱ(4 g/kg)可降低小鼠血清CHO活性(P<0.05);AE-Ⅰ、Ⅱ均可不同程度地改善肝脏病理组织性损伤。结论AE-Ⅰ、AE-Ⅱ对小鼠急性酒精性肝损伤具有保护作用。