均匀设计法优化大孔树脂纯化无患子皂苷的工艺

以无患子皂苷的饱和吸附量和解吸率为指标,从5种树脂中筛选出D101型大孔树脂纯化无患子总皂苷,进一步采用均匀设计考察了上样药液的药物浓度、pH和流速,洗脱流速及洗脱剂用量等因素对无患子皂苷收率及在洗脱物总量中比例的影响.所得最优工艺为:上样药液浓度10.6 mg/ml、药液pH 5.0、上样流速2.0 ml/min、洗脱流速3.5 ml/min、洗脱溶剂为70％乙醇(3.5 BV),所得产品中无患子皂苷占洗脱物总量的82％,收率达25％.     

无患子皂苷的提取及抑菌性研究

目的 优化无患子皂苷的提取工艺,并测定提取物的抑菌活性.方法 本研究起止时间为2018年3月至2019年3月.以乙醇为提取剂,采用超声波辅助法,通过正交试验对无患子皂苷的提取工艺进行研究;采用滤纸片扩散法测定提取物对细菌和真菌的抑制效果.结果 无患子皂苷的最佳提取工艺是以70％的乙醇为提取溶剂,料液比为1:5,超声提取60 min,共提取3次;无患子皂苷提取物对金黄色葡萄球菌、枯草芽孢杆菌和大肠杆菌等细菌的抑菌效果不明显,但可以显著抑菌真菌的生长,对青霉菌、白色念珠菌和黑曲霉的最小抑菌浓度分别为0.05 g/mL、0.11 g/mL和0.44 g/mL(生药材/提取液).结论 无患子皂苷的超声辅助提取法工艺稳定,提取物得率高,且对真菌抑菌效果显著,有很好的开发价值.     

核磁共振法测定非离子表面活性剂 HLB 值的研究 2.几种混合体系 HLB 值的测定与计算

本文应用核磁共振法(NMR)测定了几种混合体系的 HLB 值与混合体系中各组分的 HLB 值。实验结果表明,混合体系中各组分在核磁共振图谱中的积分曲线高度也具有加和性。混合体系的 HLB 值是体系中各组分 HLB 值的加权平均值。因此,对混合体系的 HLB 值可以应用 NMR 法直接测定,也可应用 NMR 法测定各组分的 HLB值,通过计算求得,计算值与实测值完全一致。     

酸枣仁颗粒中酸枣仁皂苷A和酸枣仁皂苷B的含量测定

目的建立酸枣仁颗粒中酸枣仁皂苷A和酸枣仁皂苷B的含量测定方法。方法采用反相高效液相色谱法，分析柱为Hypersil C18柱，以乙腈和水为流动相的二元梯度洗脱方法，检测波长为201nm，流速为1 mL／min。结果酸枣仁皂苷A进样量在0．50-1．98μg与峰面积呈良好的线性关系（r=0.9998，n=5），平均回收率为99．41％；酸枣仁皂苷B进样量在0．66～2．09μg与峰面积呈良好的线性关系（r=0．9998，n=5），平均回收率为99．34％。结论该法简便、快速、重现性好，适用于酸枣仁颗粒中酸枣仁皂苷A、酸枣仁皂苷B的定量分析。     

心灵丸中三七皂苷R1、人参皂苷Rg和Rb1的含量测定

目的建立同时测定心灵丸中三七皂苷R1、人参皂苷Rg1和人参皂苷Rb1含量的高效液相色谱（HPLC）法。方法色谱柱为Agilent Hypersil ODS柱（250mm×4．0mm,5μm）,流动相A为乙腈,B为水,梯度洗脱（0min 19％A→12min 19％A→60min 36％A）,流速为1．0mL／min,检测波长为203nm。结果三七皂苷R1进样量在0．1378～2．7560μg范围内与峰面积线性关系良好,r=0．9997,平均回收率为98．95％,RSD为0．67％;人参皂苷Rg1进样量在0．5672-11．3440μg范围内与峰面积线性关系良好,r=0．9999,平均回收率为99．10％,RSD为0．29％;人参皂苷Rb1进样量在0．4186～8．3720μg范围内与峰面积线性关系良好,r=0．9999,平均回收率为99．02％,RSD为0．42％。结论HPLC法简便准确、专属性强,可用于心灵丸的质量控制。     

Bell麻痹早期治疗的临床研究

目的探讨Bell麻痹早期治疗的最佳方法。方法将103例Bell麻痹急性期患者随机分为地塞米松合用三七总皂苷组（35例，A组）、地塞米松组（34例，B组）、三七总皂苷组（34例、C组），各组基础治疗均采用泛昔洛韦等药物及早期康复治疗，均在发病7d内给予相应治疗。采用H-B面神经功能恢复评定标准，分别于治疗前后评定面神经麻痹等级。结果治疗前三组H-B面瘫等级分布具有可比性。治疗1个月三组患者H-B面神经功能恢复经K-W秩和检验，P值为0．001，P〈0．05，差异有统计学意义，三组间每两组比较，A组面神经功能恢复优于B组与C组，差异有统计学意义（P值分别为0．003，0．002，P值均小于0．05）；而B组与C组之间面神经功能恢复无明显差异，差异无统计学意义（P值为0．393、P〉0．05），按百分比做疗效比较，结果三组总有效率均分别为100％，治愈与显效总和：A组为97％，B组为68％，C组为59％。A组疗效明显优于B、C组，而B、C组间疗效大致相同。结论地塞米松合用三七总皂苷综合治疗对Bell麻痹的效果明显优于单纯一种药物治疗。     

无患子皂苷对高脂血症大鼠血脂代谢的影响和对血管内皮功能的保护作用

目的 探讨无惠子皂苷对高脂血症大鼠血脂代谢的影响及其血管内皮功能的保护作用.方法 采用高脂饲料喂养建立大鼠高脂血症模型,同时用无患子皂苷水溶液0.486 g/(kg·d)或0.054 g/(kg·d)、辛伐他汀水溶液0.010 8 g/(kg·d)灌胃给药.第30天末从腹主动脉取血测血清甘油三酯(TG)、总胆田醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)、超氧化物歧化酶(SOD)以及检测血浆前列腺素I2(PGI2)和血栓素A2(TXA2)水平.结果 用药30 d后,各给药组血清中TG,TC,LDL-C,MDA和血浆中血栓素B2水平明显低于模型对照组(P＜0.01),SOD和6-酮-前列腺素F1α水平明显低于模型对照组(P＜0.01).结论 无患子皂苷可调节高脂血症模型大鼠血脂水平,并对血浆血栓素B2及6-酮-前列腺素F1α产生一定影响.     

水提过程中粉碎对酸枣仁中酸枣仁皂苷A溶出的影响

目的研究粉碎与未粉碎酸枣仁所含有效成分酸枣仁皂苷A在水提取过程中的溶出是否有差异。方法采用高效液相色谱法测定粉碎与未粉碎酸枣仁的酸枣仁皂苷A含量。色谱枉为Agilent C18柱（250mm×4．6mm，5μm），流动相为甲醇-水（65：35），流速为1．0mL／min，蒸发光散射检测器漂移管温度110℃，载气流量2．4L／min。结果在未粉碎的酸枣仁水提样品中未检测出酸枣仁皂苷A，而粉碎后的酸枣仁水提样品的酸枣仁皂苷A含量为0．0090％。结论临床应用时，酸枣仁宜粉碎。     

高效液相色谱法测定三七血伤宁散中三七皂苷R1、人参皂苷Rg1和Rb1的含量

目的建立高效液相色谱法测定三七血伤宁散中三七皂苷R1、人参皂苷Rg1和人参皂苷Rb1的含量。方法采用色谱柱ODSHypersil C18柱（4．6mm×250mm,5μm）,以乙腈（A）-水（B）为流动相,进行梯度洗脱（0～25min,20％A,25-75min,20％～35％A）,流速：1．0mL·min^-1,柱温：35℃,检测波长：203nm。结果三七皂苷R1在0．225-5．625μg与峰面积线性关系良好,r=1．0000,平均加样回收率为100．06％,人参皂苷Rg1在2．076=20．76μg与峰面积线性关系良好,r=0．9997,平均加样回收率为99．92％,人参皂苷Rb1在2．056～20．56魑与峰面积线性关系良好,r=0．9998,平均加样回收率为96．91％。结论本法准确可靠、灵敏度高、重现性好,可作为该产品质量控制的方法。     

RRLC法分离分析人参中的人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1

目的：用快速分离液相色谱法分离测定人参中人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1，的含量。方法：采用ZOBAX SB—C18柱（1．8μm，3．0mm×50mm）；流动相：乙腈（A）-水（B），梯度洗脱（0～14min，19％A；14～24min，19％A→36％A；24～26min，36％A）；流速：1．0mL·min^-1；检测波长：203nm；柱温：35℃。结果：人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1的线性范围分别为0．077～1．537μg、0.058～1．156μg和0.078～1．563μg，相关系数均为0．9999。平均加样回收率（n=6）分别为98．3％，98．7％，99．2％；RSD分别为0．9％，1．0％，0．5％。结论：本方法具有快速、准确，重复性好等特点，适合于人参的含量测定。     

A simple method for the selection of a suitable emulsifier based on color difference

The purpose of this study was to establish a simple and rapid method for selecting a nonionic surfactant to prepare an emulsion that can maintain a stable emulsification phase. As an index of the degree of emulsification, the white chromaticity of the prepared sample was measured using a color difference meter. When liquid paraffin was used as an oil, the color difference (dE(H)) was shown as a change in a V-shaped curve depending on changes in the hydrophile-lipophile balance (HLB) number of sorbitan ester, polyoxyethylene sorbitan ester, or polyethyleneglycol ester. Although there was a difference in the minimal value of dE(H) in these experiments, the dE(H) was similar to the required HLB of liquid paraffin (HLB=10). On the other hand, no relationship was found between the HLB number and color difference when polyglycerol ester was used. It seems that there was possibility of the effect by the lowering of apparent HLB with a collapse of the hydration. These results indicate that color difference could be utilized for the selection of surfactants, except for polyglycerol ester.     

精制蛋黄卵磷脂亲水-亲油平衡值测定及其在鸦胆子油乳注射液中的应用

目的以亲水-亲脂平衡值为指标考察精制蛋黄卵磷脂在水中和油中的分散特性并研究其在鸦胆子油乳注射液中的应用。方法采用核磁共振波谱(NMR)法,根据其化学位移值及亲水基团与亲油基团质子数相对比值(R)计算亲水-亲脂平衡值。结果精制蛋黄卵磷脂在水中具有良好的分散性。结论可用精制蛋黄卵磷脂代替豆磷脂作乳化剂制备鸦胆子油乳注射液。     

Some considerations about the hydrophilic-lipophilic balance system

The methods and results obtained by Griffin et al. in the determination of the hydrophilic-lipophilic balance (HLB) values of non-ionic surfactants and of required HLB values of oil mixtures are reviewed in the present work. HLB values published by Griffin were compared with those obtained by calculations from theoretic chemical formulas. Griffin HLB values of polyoxyethylene alkyl ethers, polyoxyethylene monoesters and propylene glycol monoesters coincide with those obtained from such theoretical chemical formulations. These results demonstrate that, for these surfactants, Griffin did not experimentally obtain their HLB values, but instead calculated them from theoretic formulae. For the calculation of the HLB values of glycerol monostearate, sorbitan fatty acid esters and polyoxyethylene sorbitan fatty acid esters, Griffin's assumptions were possibly based upon the mean saponification values of the ester and the acid of the fatty acid. It is concluded that the HLB values of non-ionic surfactants were not rigorously defined. Moreover, Griffin could not demonstrate the validity of the assumption that individual required HLB values can be added up to obtain the overall required HLB value of an oil mixture. The HLB and required HLB values published by Griffin should only be taken as approximate guidelines.     

Effect of HLB of additives on the properties and drug release from the glyceryl monooleate matrices.

Glyceryl monooleate (GMO) is an amphiphilic surfactant, which as such can solubilize hydrophilic, lipophilic and amphiphilic drug molecules in its different polarity regions. Addition of additives with different polarities in GMO leads to change in phase behavior and related properties of GMO. Effect of the additives with different hydrophilic lipophilic balance (HLB; 1.5, 3, 4, 5, 7, 10 and 11) in GMO matrices on its phase transformation, rheological properties, mechanical properties, wetting and release behavior was investigated. Polarizing light microscopy showed that the GMO matrices incorporated with lower HLB additive (1.5, 3, 4 and 5) form cubic phase at higher rate while lamellar phase was prominent for matrices with additive of HLB 7, 10 and 11. The diametrical crushing strength and viscosity was decreased with increased HLB of additive. Lower HLB additives enhanced contact angle as compared to plain matrices and high HLB additives induced change in solid-liquid interface from hydrophobic to hydrophilic leading to decline in contact angle. Percent swelling of matrices was increased linearly with increase in HLB of additives. Tensiometric method was used for determination of bioadhesive strength of hydrated matrices and it was observed that matrices with additives of HLB 10 presented highest bioadhesion due to higher rate of hydration and formation of lamellar phase. As the HLB of additives in matrix increased, release was shifted from anomalous (non-Fickian) diffusion and/or partially erosion-controlled release to Fickian diffusion. Initial lag was observed for drug released from matrices with additive of HLB 1.5, 3, 4 and 5. Thus incorporation of the additives of different HLB changed molecular packing, which significantly affected drug release pattern.     

Intestinal permeation and metabolism of a model peptide (leuprolide) and mechanisms of permeation enhancement by non-ionic surfactants

The intestinal permeability of leuprolide, a model nonapeptidel was determined using an in vitro model involving everted intestinal sacs of rat. Degradation of leuprolide by intestinal proteolytic enzymes was suppressed with a mixture of protease inhibitors which was shown to completely inhibit degradation in separate experiments using intestinal homogenates. This allowed the true permeability coefficient of leuprolide to be determined. The enhancement of this intestinal permeability by the Igepal CO’ homologue series of surfactants was investigated using members of this series with hydrophilic-lipophilic balance values (HLB) ranging between 12 and 19. Enhancement showed a non-monotonic dependence on HLB with a maximum at HLB = 15, while at both lower and higher HLB values an enhancement decrease was observed. Surfactant uptake into the tissue showed a similar non-monotonic dependence on HLB. On the other hand, red blood cell lysis and lecithin solubilization potencies of the Igepal CO showed a monotonic decrease with increasing HLB within the HLB range studied. Hence, it is suggested that the process of permeation enhancement should be dissociated from that of membrane solubilization in terms of the mechanism of surfactant-membrane interaction. While membrane disruption, for example, in the case of hemolysis, seems to be correlated with phospholipid solubilization it does not appear to be a prerequisite for permeation enhancement. Permeability increase of the plasma membrane may conceivably be accomplished by surfactant incorporation into the bilayer causing highly permeable disorder points and/or an increased membrane fluidity.     

Determination of the required HLB values of some essential oils

The required HLB values of eucalyptus, lippia and peppermint essential oils were determined using droplet size analysis and turbidimetric method on emulsions prepared with emulsifier blends of varying HLB values. The percentage increase in mean droplet diameter and the degree of dispersion of droplet sizes were determined before and after centrifugation of the emulsions. The HLB value of the emulsion with the least dispersion ratio or the least percentage increase in mean droplet diameter was taken as the required HLB of the respective essential oil. The turbidimetric method was validated by the existence of correlation (r=-0.958) between the mean droplet diameter and the turbidity of the emulsions. The turbidity curve went through a maximum at the HLB value where the mean droplet diameter was least. Based on these methods, the required HLB values of eucalyptus, lippia and peppermint oils were determined as 9.8, 12.1 and 12.3, respectively (P<0.05). Liquid paraffin was used as a reference standard and its required HLB fell within literature value.     

核磁共振法测定非离子表面活性剂HLB值的研究 1.Span和Tween类及其混合物

本文用核磁共振法研究了制剂中常用的 Span 类与 Tween 类以及混合时 HLB 值的测定,建立了求算 HLB 值的方程式:HLB=18.24R+1.80,式中 R=(ΣH_((W))/(ΣH_((W))+ΣH_((0))),该式对此类单一的和混合的非离子表面活性剂都适用。此方法快速,无破坏性,需样品量少。     

Optimization of liberation of theophylline derivatives from Gelucire matrix tablets]

Matrix tablets containing theophylline, etofylline, dyphylline and proxyphylline were prepared with saturated polyglycolysed glycerides whose melting point was 50 degrees C and HLB were 2 and 13 (Gelucires 50/02 and 50/13), in order to eliminate the melting point influence and to have extreme values of HLB. The influence of two parameters was studied: HLB of the mixtures of Gelucires and drug solubility. Drug release was found to increase as these two parameters rose, the main factor being HLB value. Multiple linear regression was used to evaluate their influence. The mathematical model obtained was employed to optimize the release of each active ingredient from the tablets made of mixtures of the two Gelucires with HLB ranging from 3 to 4 depending on drug solubility.     

The influence of HLB on the encapsulation of oils by complex coacervation

Abstract

Microcapsules are used for the formulation of drug controlled release and drug targeting dosage forms. Encapsulated hydrophobic drugs are often applied as their solutions in plant oils. The uptake of the oils in the complex coacervate microcapsules can be improved by the addition of surfactants. In this study, soybean, olive and peanut oils were chosen as the representatives of plant oils. The well characterized complex coacervation of gelatin and acacia has been used to produce the microcapsules. The amount of encapsulated oil has been determined gravimetrically. The encapsulation of the oils was high (75–80%). When the surfactants with HLB values from 1.8 to 6.7 were used, the amount of encapsulated oil was high (65–85%). A significant decrease of the oil content in the microcapsules was found when Tween 61 with HLB = 9.6 had been added into the mixture. No oil was found inside the microcapsules from the coacervate emulsion mixture containing Tween 81 (HLB = 10) and Tween 80 (HLB = 15), respectively. The results of the experiment confirm the dependence of hydrophobic substance encapsulation on the HLB published recently for Squalan