纳他霉素纳米乳的制备及其质量评价

目的:研制纳他霉素纳米乳制剂并对其进行质量评价。方法:采用伪三元相图法进行配方筛选,并观测纳米乳的形态、粒径分布、Zeta电位。通过紫外分光光度法测定纳他霉素纳米乳中纳他霉素的含量。最后通过光照和加速实验对其稳定性进行考察。结果:制备的纳他霉素纳米乳,在透射电镜下观察为球状液滴,平均粒径为10.5 nm(25℃),Zeta电位为+13.0 mV(25℃,pH 3.5)。纳他霉素纳米乳中纳他霉素的平均含量为(17.31±0.02)g.L-1。在避光条件下保存,可长期保持稳定。结论:纳他霉素纳米乳制备工艺简单,切实可行,性质稳定,是一种很有前途的纳他霉素新制剂。     

γ-亚麻酸甲酯纳米乳的制备及质量评价

目的研制γ-亚麻酸甲酯纳米乳制剂并对其进行质量评价。方法优选γ-亚麻酸甲酯纳米乳剂处方,评价制剂的结构、形态、分散性及稳定性。结果以聚乙二醇400作助表面活性剂,当表面活性剂聚山梨酯80与γ-亚麻酸甲酯质量比为1∶2时,制得了γ-亚麻酸甲酯纳米乳剂,γ-亚麻酸甲酯在乳剂中含量为25%。γ-亚麻酸甲酯纳米乳在透射电镜下呈圆球形,平均粒径为60 nm,室温保存6个月后纳米乳分散均匀且稳定好。结论获得了性质稳定的γ-亚麻酸甲酯纳米乳,为开发γ-亚麻酸注射剂奠定了基础。     

熊果酸纳米乳的制备及质量评价

目的研究熊果酸纳米乳的制备和质量评价。方法考察熊果酸在不同油相、表面活性剂和助表面活性剂中的平衡溶解度,并通过水滴定法绘制伪三元相图,确定最优的Km值和纳米乳处方,研制出适合经口给药的纳米乳制剂。分别采用离心法考察熊果酸纳米乳的外观和形态,通过电导率判断其类型以及使用激光粒度测定仪测定粒径大小,使用电子透射显微镜观察纳米乳形态。用HPLC测定含药纳米乳中熊果酸的含量,同时考察其稳定性、载药量、包封率等。结果优选处方为Cremophor RH40-聚乙二醇400-油酸乙酯(52.5∶17.5∶30,m/m/m)。所制熊果酸纳米乳为澄清或略带乳光的淡蓝色液体,离心后稳定不分层,电导率为33.7 ms·m~(-1),平均粒径(53.09±10.47)nm,呈Gauss分布,纳米乳液滴,外观圆整,大小均一,状态良好。HPLC检测其稳定性良好,包封率为86.5%,载药量为0.425mg·mL~(-1)。结论熊果酸在纳米乳中的溶解度明显增加,所制得的含药纳米乳易于制备且质量稳定,可以通过制作熊果酸纳米乳的方法来提高熊果酸的生物利用度。     

醋酸泼尼松龙纳米乳的制备

目的制备醋酸泼尼松龙纳米乳,并观察其稳定性。方法聚乙二醇,醋酸泼尼松龙和卵磷脂的氯仿溶液在氮气流下减压成膜,加入经水化超声处理的大豆油,进一步处理后使其微乳化。结果粒径50~100nm,包封率≥90%。结论该工艺制备了粒径小于100nm的醋酸泼泥松龙纳米乳,有较好的稳定性。     

葡萄籽中原花青素类成分的制备及其止泻活性评价

目的 研究特定聚合度原花青素为主要成分的葡萄籽提取物在腹泻治疗中的新用途。方法 将葡萄籽进行粉碎、粗提、精制并分级沉淀后得到6个部位,以大鼠腹泻模型评价葡萄籽原花青素提取物各部位的止泻活性,并对有效部位的总原花青素含量、平均聚合度和主要单体组成等特性进行分析。结果 来源于葡萄籽的多聚原花青素部位F4对应激性腹泻模型有显著活性,而其他纯化部位和总提物并无此作用。结论 F4部位在主要原花青素单体组成和含量上与总原花青素及其他部位相比并无差异,但在平均聚合度上差异明显,表明F4部位的止泻活性与其特定的聚合度密切相关。     

雷公藤多苷纳米乳的制备及其理化性质评价

目的:研制雷公藤多苷纳米乳并对其理化性能、稳定性等进行评价。方法:结合雷公藤多苷在不同的油和表面活性剂中的溶解度以及伪三元相图的绘制,研制雷公藤多苷纳米乳,并对其类型、形态、粒径、理化参数及稳定性进行考察。结果:雷公藤多苷在聚氧乙烯氢化蓖麻油(RH-40)和肉豆蔻酸异丙酯(IPM)中溶解度较大,且以RH-40为表面活性剂,IPM为油相时纳米乳形成区域最大,最终纳米乳配方确定为RH-40∶IPM∶水,重量比为27∶3.3∶69.7,其中可添加浓度小于5%的透皮促渗剂氮酮;制备的雷公藤多苷纳米乳为棕黄色,澄清透明,流动性良好的O/W型纳米乳,该纳米乳粒子形态主要为圆球形,平均粒径为23.6nm,稳定性良好。结论:研制的雷公藤多苷纳米乳是质量稳定的新制剂。     

原花青素药用研究进展

原花青素(proanthocyanidin,PC)是一大类多酚类化合物的总称,由儿茶素、表儿茶素及表儿茶素没食子酸酯通过C4～C6或C4～C8连接而成的不同聚合度的混合物[1]。按聚合度的大小,通常将二聚体～四聚体称为低聚体,将五聚体以上的称为高聚体,不同聚合度的原花青素具有不同的化学与生物活性     

原花青素的药理学研究进展

综述近几年来国内外对原花青素在抗氧化、保护心血管、调节免疫活性、保护肝肾功能、抗诱变、抗病毒、抗癌、抗溃疡、抗微生物、促进毛发生长等生物药理活性的研究进展。     

纳米乳的研究进展及其应用

综述了纳米乳的制备工艺、评价体系、稳定性及在药剂学领域中的应用.     

原花青素防治心血管疾病的研究进展

原花青素因优异的抗氧化性能和显著的清除自由基能力而在多种心血管疾病发生、发展的各个阶段均显示确切的预防作用,是具有广阔发展前景的植物药     

Preparation and in vivo evaluation of indomethacin loaded true nanoemulsions

Indomethacin, a potent nonsteroidal anti-inflammatory drug, has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of indomethacin produces serious gastrointestinal adverse effects. Therefore the aim of the present investigation was to evaluate the anti-inflammatory effects, skin irritation, activation energy and histopathology of indomethacin from transdermally applied true nanoemulsion. The anti-inflammatory effects of true nanoemulsions were compared with marketed Indobene^® gel on carrageenan-induced paw edema in rats. Skin irritation tests were performed on Wistar rats for 14 days. The % inhibition value after 12 h application was significant for optimized formulation F6 (83) as compared to marketed Indobene^® gel (P<0.01). Results of skin irritation test indicated that developed true nanoemulsion is safe for human use. The significant decrease in activation energy (1.396 kcal/mol) for indomethacin across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (P<0.05). From these results it was concluded that the developed nanoemulsion have great potential for transdermal application of indomethacin.     

Preparation,characterization, and antimicrobial activity of nanoemulsions incorporating citral essential oil

Citral is a typical essential oil used in the food, cosmetic, and drug industries and has shown antimicrobial activity against microorganisms. Citral is unstable and hydrophobic under normal storage conditions, so it can easily lose its bactericide activity. Nanoemulsion technology is an excellent way to hydrophilize, microencapsulate, and protect this compound. In our studies, we used a mixed surfactant to form citral-in-water nanoemulsions, and attempted to optimize the formula for preparing nanoemulsions. Citral-in-water nanoemulsions formed at S_o 0.4 to 0.6 and ultrasonic power of 18 W for 120 seconds resulted in a droplet size of < 100 nm for nanoemulsions. The observed antimicrobial activities were significantly affected by the formulation of the nanoemulsions. The observed relationship between the formulation and activity can lead to the rational design of nanoemulsion-based delivery systems for essential oils, based on the desired function of antimicrobials in the food, cosmetics, and agrochemical industries.     

乳酸杆菌栓剂的研制及其质量控制

目的：研制一种含活乳酸杆菌的栓剂并对其进行质量评价。方法：选用甘油、明胶等基质与乳酸杆菌培养液混合制备栓剂，进行鉴别、含量测定、融变时限和稳定性试验。结果：制备的栓剂符合所定的质量标准，乳酸杆菌栓于4℃冷藏保存1年，乳酸杆菌浓度和外观等几乎无变化；室温保存1年浓度降低；加速试验3个月时无活菌存在。结论：乳酸杆菌栓适宜4℃冷藏保存，其制备工艺简单易行，是一种很有研究价值的新型微生态制剂。     

Multiple linear regression applied to predicting droplet size of complex perfluorocarbon nanoemulsions for biomedical applications

Multiple linear regression (MLR) modeling as a novel methodological advancement for design, development, and optimization of perfluorocarbon nanoemulsions (PFC NEs) is presented. The goal of the presented work is to develop MLR methods applicable to design, development, and optimization of PFC NEs in broad range of biomedical uses. Depending on the intended use of PFC NEs as either therapeutics or diagnostics, NE composition differs in respect to specific applications (e.g. magnetic resonance imaging, drug delivery, etc). PFC NE composition can significantly impact on PFC NE droplet size which impacts the NE performance and quality. We demonstrated earlier that microfluidization combined with sonication produces stable emulsions with high level of reproducibility. The goal of the presented work was to establish correlation between droplet size and composition in complex PFC-in-oil-in-water NEs while manufacturing process parameters are kept constant. Under these conditions, we demonstrate that MLR model can predict droplet size based on formulation variables such as amount and type of PFC oil and hydrocarbon oil. To the best of our knowledge, this is the first report where PFC NE composition was directly related to its colloidal properties and MLR used to predict colloidal properties from composition variables.     

原花青素对大鼠心肌缺血-再灌注损伤的保护作用

目的探讨原花青素对大鼠心肌缺血-再灌注损伤引起的氧化应激损伤的保护作用。方法建立心肌缺血-再灌注模型。再灌注结束后采血,测定丙二醛(MDA)、超氧化物歧化酶(SOD)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH),测量心肌梗死面积。结果原花青素能明显降低血浆中MDA、AST和LDH的含量(P<0.05),提高SOD活性(P<0.05),减少心肌梗死面积(P<0.05)。结论原花青素对大鼠心肌缺血-再灌注损伤引起的氧化应激损伤的有保护作用。     

Preparation,preliminary pharmacokinetics and brain tissue distribution of Tanshinone IIA and Tetramethylpyrazine composite nanoemulsions

Objective: Tanshinone IIA (TSN) and Tetramethylpyrazine (TMP) were combined in a composite, oil-in-water nanoemulsions (TSN/TMP O/W NEs) was prepared to prolong in vitro and vivo circulation time, and enhance the bioavailability of TSN.

Material and methods: Physicochemical characterization of TSN/TMP O/W NEs was characterized systematically. The in vitro dissolution and in vivo pharmacokinetic experiments of TSN/TMP O/W NEs were also evaluated.

Result: A formulation was optimized, yielding a 32.5?nm average particle size, an encapsulation efficiency of over 95 %, and were spherical in shape as shown by TEM. TSN/TMP O/W NEs were shown to extend the release and availability in vitro compared to raw compounds. In pharmacokinetic study, the AUC_0→∞ and t_1/2 of the TSN/TMP O/W NEs were 481.50?mg/L*min and 346.39?min higher than TSN solution, respectively. Brain tissue concentration of TSN was enhanced with TSN/TMP O/W NEs over raw TSN and even TSN O/W NEs.

Conclusions: Therefore, nanoemulsions are an effective carrier to increase encapsulation efficiency of drugs, improve bioavailability and brain penetration for TSN – which is further enhanced by pairing with the co-delivery of TMP, providing a promising drug delivery.     

多种油脂肪乳注射液制备工艺与质量评价的初步研究

目的 研制多种油脂肪乳注射液并初步考察其质量.方法 参考原研制剂SMOFlipid(R)的处方组成,采用二步法制备多种油脂肪乳注射液,以外观性状、粒径、pH值、含量和有关物质等为评价指标,考察乳化温度、卵磷脂加入方式、初乳剪切转速、时间以及高压均质压力、灭菌温度等关键工艺参数对产品质量的影响,由此确定样品的制备工艺.在此基础上,采用溶血性、血管刺激性试验初步评价样品的安全性;采用长期试验法考察其稳定性.结果 优选的制备工艺为乳化温度60℃、剪切速度1.9×104 r·min-、剪切时间10 min、均质压力8000 psi,灭菌条件121℃、8 min.自制多种油脂肪乳注射液的平均粒径为306.9 nm,Zeta电位为-30 mV,在25℃条件下稳定性良好,溶血性、血管刺激性检查均符合要求.结论 温度与时间、高压均质压力、灭菌条件等因素对初乳的质量影响较大,应进行严格控制,自制产品的质量可达到原研制剂相关质量标准的要求.     

葡萄籽原花青素对小鼠深低温脑缺血-再灌注损伤的影响

目的探讨葡萄籽原花青素(GSPE)对小鼠脑缺血-再灌注(I-R)损伤的保护作用。方法 60只C57/BL6小鼠随机均分为GSPE(A)组、模型(B)组和假手术(C)组,建立深低温I-R模型,再灌注24 h后处死小鼠取脑,RT-PCR技术检测小鼠脑组织半胱天冬氨酸蛋白酶(Caspase)3mRNA,TUNEL法检测小鼠大脑皮层细胞凋亡。结果与C组比较,A组和B组Caspase-3 mRNA表达和细胞凋亡明显增加(P<0.05);而A组各观察指标低于B组(P<0.05)。结论 GSPE对深低温I-R损伤鼠脑有保护作用。     

Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals,supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems

ABSTRACT

Introduction: The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability.

Areas covered: The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given.

Expert opinion: Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.