羧甲基壳聚糖/聚乙烯醇水凝胶处方及制备工艺优化

目的：优选羧甲基壳聚糖（CMCS）／聚乙烯醇（PVA）水凝胶的处方及制备工艺；初步考察载药水凝胶的体外释药规律。方法：合成不同取代度的CMCS；以羧甲基壳聚糖的取代度，2％戊二醛的用量及温度为考察因素，各取三水平，以水凝胶在pH1．2溶液中的膨胀率为考察指标进行L9（3^4）正交实验；并以甲硝唑为模型药物，对水凝胶的体外释药做初步考察。结果：取代度为0．38的CMCS，在0．2mL的2％戊二醛做交联剂于室温下交联，有最大膨胀率（24．54±1．04）（n=3）；以最佳条件制备的甲硝唑水凝胶于0．1mol·L^-1盐酸溶液中在8h内累积释药率达（89．95±1．05）％（n=3）。结论：CMCS/PVA水凝胶最佳处方在pH1．2时具有理想的膨胀率，可做为胃部释药载体进一步研究。     

Development of Meloxicam-Loaded Electrospun Polyvinyl Alcohol Mats as a Transdermal Therapeutic Agent

This study reports on the use of electrospun polyvinyl alcohol (PVA) nanofiber mats loaded with meloxicam (MX) as a transdermal drug delivery system. The amounts of MX loaded in the base PVA solution (10% w/v solution) were 2.5, 5, 10 and 20% weight, based on the dry weight of PVA (% wt). The average diameters of these fibers ranged from 121–185 nm. In all concentrations of MX loaded in spun PVA fiber mats, an amorphous nanodispersion of MX with PVA was obtained. Both the degree of swelling and the weight loss of the electrospun PVA mats were greater than those of the as-cast PVA films. The tensile strength of the as-spun fiber mats was lower than that of the as-cast PVA films, but the strain at the maximum of the as-spun fiber mats was about six times higher than that of the as-cast PVA films. The skin permeation flux of the MX permeated from MX-loaded as-spun PVA were significantly higher than from MX-loaded as-cast PVA films, and increased when the MX content in both MX-loaded as-spun PVA and MX-loaded as-cast PVA films was increased. Our research suggests a potential use for MX-loaded electrospun PVA mats as a transdermal drug delivery system.     

Chitosan films incorporated with nettle (Urtica dioica L.) extract-loaded nanoliposomes: I. Physicochemical characterisation and antimicrobial properties

The objective of this study was to characterise and compare physical, mechanical and antimicrobial properties of chitosan-based films, containing free or nanoencapsulated nettle (Urtica dioica L.) extract (NE) at concentrations of 0, 0.5, 1 and 1.5% w/w. Nanoliposomes were prepared using soy-lecithin by thin-film hydration and sonication method to generate an average size of 107–136?nm with 70% encapsulation efficiency. The information on FT-IR reflected that some new interaction have occurred between chitosan and nanoliposomes. Despite the increasing yellowness and decreasing whiteness indexes, the nanoliposomes incorporation improved the thermal properties and mechanical stiffness and caused to decrease water vapour permeability (WVP), moisture uptake and water solubility. The possible antimicrobial activity of the films containing NE-loaded nanoliposomes against Staphylococcus aureus was decreased in comparison to free NE-incorporated films, which could be due to the inhibition effect of the encapsulation that prevents the release of NE from the matrix.     

辣椒提取物的健胃和消食作用研究

目的探讨辣椒提取物的健胃消食作用。方法采用小鼠小肠推进试验和胃排空试验、对大鼠胃酸和胃蛋白酶分泌的影响以及对豚鼠离体回肠的影响等进行健胃消食试验。结果小鼠灌服低（0．025g·kg^-1）、中（0．05g·kg^—1）、高（0．1g·kg^—1）剂量的辣椒提取物后,可显著促进小鼠胃排空和小肠推进的作用,且中剂量的辣椒提取物对小鼠的胃排空作用更强,高剂量的辣椒提取物反而起到抑制小鼠胃排空的作用;随着剂量的增大,对小鼠小肠的推进作用也逐步地减小。在阿托品对豚鼠离体回肠抑制后加入辣椒提取物能使抑制后的回肠开始兴奋。对大鼠灌服低（0．075g·kg^-1）、中（0．15g·kg^—1）、高（0．3g·kg^-1）剂量的辣椒提取物,发现辣椒提取物有促进大鼠胃酸和胃蛋白酶分泌的作用。结论辣椒提取物有健胃     

Chitosan films incorporated with nettle (Urtica Dioica L.) extract-loaded nanoliposomes: II. Antioxidant activity and release properties

Chitosan films were loaded with NE nettle (Urtica dioica L.) extract (NE) at concentrations of 0, 0.5, 1 and 1.5%w/w in the free or nanoliposomal form to obtain active and nanoactive films, respectively. The antioxidant potential of the films containing NE-loaded nanoliposomes was decreased in comparison of free NE incorporated films. Diffusion of NE to soybean oil was enough to delay the induction of the oxidation of soybean oil stored for 60 days in contact with chitosan based films. Release studies indicated that the release rate of NE in 95% ethanol simulant significantly decreased by the nanoencapsulation of NE. The diffusion coefficient (D) for chitosan films containing 1.5%w/w of free and encapsulated NE at 25?°C was 18.80 and 3.68?×?10^?7 cm² s^?1, respectively. Moreover, the formation of nanoliposomes diminished the increasing effect of temperature on the release rate as when storage temperature increased from 4?°C to 40?°C.     

醋酸纤维素水分散体的制备及性质测定

目的:制备醋酸纤维素(CA)水分散体,并测定其部分理化性质。方法:以乙酸乙酯、无水乙醇为溶剂,十二烷基硫酸钠为乳化剂,采用乳化-溶剂挥干法制备醋酸纤维素水分散体,并以沉降体积比评分为指标,通过正交实验,对结果进行直观分析和方差分析,确定了最优处方。结果:最优处方中十二炕基硫酸钠、乙醇和CA的含量分别为3 g·L-1,5％和5％,本法制得的醋酸纤维素水分散体外观良好,平均粒径162 nm,zeta电位-58．8 mV,固形物含量为8．8％,黏度为(5．2±0．7)mPa·s(n=6)。结论:自制的醋酸纤维素水分散体粒径小、固形物含量高、黏度低,能够满足包衣要求。     

真空蒸汽润药法润制浙产三棱饮片的工艺研究

目的 根据真空蒸汽润药原理,对浙产三棱进行气相置换软化,优化三棱润制工艺。方法 采用真空蒸汽润药机优化三棱润制工艺,并与传统润制方法进行比较。采用正交实验对润药工艺进行多因素考察,运用紫外分光光度法测定总黄酮的含量,以三棱醇浸出物和总黄酮的含量为综合评价指标,筛选最佳优化方案。结果 采用真空蒸汽润药软化后的三棱饮片含水量低,软化效果好,浸出物和总黄酮含量高。结论 真空蒸汽润药法可使药材在低含水量的情况下,快速、均匀地软化,还可提高三棱中有效成分的含量。     

Novel neomycin sulfate-loaded hydrogel dressing with enhanced physical dressing properties and wound-curing effect

To develop a novel neomycin sulfate-loaded hydrogel dressing (HD), numerous neomycin sulfate-loaded HDs were prepared with various amounts of polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and sodium alginate (SA) using freeze-thawing technique, and their physical dressing properties, drug release, in vivo wound curing and histopathology in diabetic-induced rats were assessed. SA had a positive effect on a swelling capacity, but a negative effect on the physical dressing properties and drug release of HD. However, PVP did the opposite. In particular, the neomycin sulfate-loaded HD composed of drug, PVA, PVP and SA at the weight ratio of 1/10/0.8/0.8 had excellent swelling and bioadhesive capacity, good elasticity and fast drug release. Moreover, this HD gave more improved wound curing effect compared to the commercial product, ensured the disappearance of granulation tissue and recovered the wound tissue to normal. Therefore, this novel neomycin sulfate-loaded HD could be an effective pharmaceutical product for the treatment of wounds.     

口腔溃疡膜的研制

目的:将原散剂研制成膜剂,利于药效的发挥.方法:以口腔溃疡散的组方为主药成分,以性状,粘附力、膜溶解时间等为考察指标,进行处方筛选及工艺优化,并进行了膜剂的影响因素试验和在人口腔的溶解试验.结果:以羟丙甲纤维素(HPMC)和聚乙烯醇(PVA)为膜材,当比例为2∶1时,膜的外观均匀,粘附力达(23.2±3.4)牛顿(N),聚丙烯酸酯II为外层制成的双层膜溶解时间为(46.7±5.2)min,其在人口腔的溶解时间为(54.0±22.3)min(n=10).结论:膜材HPMC∶PVA为2∶1时, 制成的膜剂质量最佳.双层膜可延长药膜在口腔溃疡表面的粘附与溶解时间,且可定向释放,有利于药效的发挥.     

Fabrication and characterisation of self-applicating heparin sodium microneedle patches

Abstract

The aim of this study was to develop heparin sodium loaded microneedle patches using different compositions of polyvinyl alcohol polymer and sorbitol. A vacuum micromolding technique was used to fabricate microneedle patches while heparin sodium was loaded into needle tips. Physical features of patches were evaluated by measuring thickness, width, folding endurance and swelling percentage. Patches were also characterised by optical microscopy and scanning electron microscopy to determine the microneedle length and surface morphologies. A preliminary assessment of the microneedle performance was studied by examining the in-vitro insertion to the parafilm and recording the in-vitro drug release profile. In-vivo activity of patches was confirmed by measuring activated partial thromboplastin time and histological examination of the micropierced skin tissues. Prepared patches were clear, smooth; uniform in appearance; with sharp pointed microprojections and remained intact after 1000 folding. The microneedles were stiffer in nature, as they reproduce microcavities in the parafilm membrane following hand pushing without any structural loss. Insertion study results showed successful insertion of microneedles into the parafilm. Disrupted stratum corneum evident from histological examination confirmed successful insertion of the microneedle without affecting the vasculature. In-vitro release study confirmed ～92% release of the loaded drug within 120?min. A significant prolongation of activated partial thromboplastin time (4 folds as compared to negative control) was recorded following the application of heparin sodium loaded microneedle patch onto rabbit skin. In conclusion microneedles are a valuable drug delivery system, benefiting the patients with minimal skin invasion and also allowing self-administration of heparin sodium in a sustained release manner for the management of chronic ailments.     

Zingiber cassumunar blended patches for skin application: Formulation,physicochemical properties,and in vitro studies

Our work was to study the preparation, physicochemical characterization, and in vitro characteristic of Zingiber cassumunar blended patches. The Z. cassumunar blended patches incorporating Z. cassumunar Roxb. also known as Plai were prepared from chitosan and polyvinyl alcohol with glycerin as plasticizer. They were prepared by adding all ingredients in a beaker and homogeneously mixing them. Then, they were transferred into Petri-dish and dried in hot air oven. The hydrophilic nature of the Z. cassumunar blended patches was confirmed by the moisture uptake, swelling ratio, erosion, and porosity values. The FTIR, DSC, XRD, and SEM studies showed revealed blended patches with amorphous region that was homogeneously smooth and compact in both surface and cross section dimensions. They exhibited controlled the release behavior of (E)-4-(3′,4′-dimethoxyphenyl) but-3-en-l-ol (compound D) that is the main active compound in Z. cassumunar for anti-inflammation activity. However, in in vitro skin permeation study, the compound D was accumulated in newborn pig skin more than in the receptor medium. Thus, the blended patches showed the suitable entrapment and controlled release of compound D. Accordingly, we have demonstrated that such chitosan and polyvinyl alcohol formulated patches might be developed for medical use.     

Design and Evaluation of Ethyl Cellulose Based Matrix Tablets of Ibuprofen with pH Modulated Release Kinetics

Controlled release preparations have been reported to reduce the gastro irritant and ulcerogenic effects of non steroidal antiinflammatory drugs. In the present study, an attempt was made to develop matrix tablet-based controlled release formulations of ibuprofen, using ethyl cellulose as the rate-controlling polymer. In order to prevent initial release of the drug in the acidic environment of the stomach, cellulose acetate phthalate was incorporated in the matrix in varying amounts. It was found that with increasing the proportion of ethyl cellulose in the matrix, the drug release was extended for 14-16 h. Incorporation of cellulose acetate phthalate in ethyl cellulose matrix provided very low initial release of the drug in the first 2-3 h followed by enhanced release rate in alkaline medium owing to the high solubility of cellulose acetate phthalate at basic pH which led to creation of a porous matrix. It was concluded that combination of cellulose acetate phthalate with ethyl cellulose in the matrix base can be an effective means of developing a controlled release formulation of ibuprofen with very low initial release followed with controlled release up to 14-16 h.     

Enhanced film-forming properties for ethyl cellulose and starch acetate using n-alkenyl succinic anhydrides as novel plasticizers

Purpose: The aim of this study was to investigate the ability of n-alkenyl succinic anhydrides (n-ASAs) to improve the film-forming characteristics of a novel coating polymer, potato starch acetate degree of substitution 2.8 (SA). n-ASAs were also applied to improve the otherwise brittle properties of ethyl cellulose (EC) aqueous dispersion (Aquacoat^®) and EC solvent-based films. Methods: The effectiveness of two n-ASAs, 2-octenyl succinic anhydride (OSA) and 2-dodecen-1-ylsuccinic anhydride were evaluated as plasticizers. Mechanical properties, both water vapor and drug permeabilities, and glass transition temperatures of the cast free films were measured. Triethyl citrate and dibutyl sebacate were used as reference plasticizers. Results: The long hydrocarbon chain of n-ASA, with its accessible carbonyl groups, enabled a strong plasticization effect on the tested polymers. Due to the excellent mechanical properties (i.e., a tough film structure with considerable flexibility) and low permeability of the plasticized films, n-ASAs, and especially OSA proved to be an ideal plasticizer particularly for EC based coatings. Also, the EC aqueous dispersion plasticized with n-ASAs resulted in a markedly enhanced coalescence of the colloidal polymer particles, even at low drying temperatures. Conclusions: In applications where a coating with high flexibility is required, n-ASAs can be used as plasticizers at moderately high concentrations (up to 60–70%, w/w) without losing the high tensile strength, excellent toughness and low permeability of EC and SA films.     

Diclofenac sodium loaded-cellulose acetate butyrate: Effect of processing variables on microparticles properties,drug release kinetics and ulcerogenic activity

The aim of this study was to develop and characterize diclofenac sodium loaded-cellulose acetate butyrate microparticles in order to obtain a controlled-release system. The influence of the type of polymer, the volume and composition of the internal phase, drug loading, surfactant concentration and additive added on microparticles characteristics (particle size, encapsulation efficiency, surface morphology and in vitro release profiles) was studied to optimize the microparticles system. The resultant microparticles were evaluated for the recovery, average particle size, drug loading and incorporation efficiency. The microparticles exhibited good flowing nature and compressibility index when compared to pure drug. Dissolution rate of diclofenac sodium in phosphate buffer (pH 6.8) increased with increases in initial drug loading, surfactant concentration and addition of alcohol as co-solvent but decreased with increases in the concentration of additives such as Gantrez® AN or Eudragit S100 in the internal phase. The dissolution data showed a Higuchi diffusion pattern for most of the formulations. About 56–81% reduction in ulcerogenic activity was observed with microparticles containing Eudragit S100 17–25%, based on total polymer concentration, when compared with pure diclofenac sodium.     

Fabrication and characterization of Agarwood extract-loaded nanocapsules and evaluation of their toxicity and anti-inflammatory activity on RAW 264.7 cells and in zebrafish embryos

Aquilaria malaccensis has been traditionally used to treat several medical disorders including inflammation. However, the traditional claims of this plant as an anti-inflammatory agent has not been substantially evaluated using modern scientific techniques. The main objective of this study was to evaluate the anti-inflammatory effect of Aquilaria malacensis leaf extract (ALEX-M) and potentiate its activity through nano-encapsulation. The extract-loaded nanocapsules were fabricated using water-in-oil-in-water (w/o/w) emulsion method and characterized via multiple techniques including DLS, TEM, FTIR, and TGA. The toxicity and the anti-inflammatory activity of ALEX-M and the extract-loaded nanocapsules (ALEX-M-PNCs) were evaluated in-vitro on RAW 264.7 macrophages and in-vivo on zebrafish embryos. The nanocapsules demonstrated spherical shape with mean particle diameter of 167.13 ± 1.24 nm, narrow size distribution (PDI = 0.29 ± 0.01), and high encapsulation efficiency (87.36 ± 1.81%). ALEX-M demonstrated high viability at high concentrations in RAW 264.7 cells and zebrafish embryos, however, ALEX-M-PNCs showed relatively higher cytotoxicity. Both free and nanoencapsulated extract expressed anti-inflammatory effects through significant reduction of the pro-inflammatory mediator nitric oxide (NO) production in LPS/IFNγ-stimulated RAW 264.7 macrophages and zebrafish embryos in a concentration-dependent manner. The findings highlight that ALEX-M can be recognized as a potential anti-inflammatory agent, and its anti-inflammatory activity can be potentiated by nano-encapsulation. Further studies are warranted toward investigation of the mechanistic and immunomodulatory roles of ALEX-M.     

Oral 4-week and 13-week toxicity studies of polyvinyl acetate vinyl laurate copolymer in rats

Polyvinyl acetate vinyl laurate copolymer (PVAcVL) is a useful component of gum base for chewing gum production. The safety of PVAcVL was examined in a 4-week and a 13-week oral toxicity study in rats. Finely powdered PVAcVL was administered with the diet at levels of 1.25%, 2.0% and 5% in the 4-week study and 1.25%, 2.5% and 5% in the 13-week study. There were no treatment related effects on mortality, bodyweight gains feed efficiency, ophthalmoscopic findings, hematological and clinical chemical parameters, neurobehavioral observations as well as gross and histopathological changes of standard organs and tissues. The highest dose tested in the 13-week study (3783 and 4396 mg/kg bw/d for males and females, respectively) proved to be a NOAEL.     

Synthesis of the perdeuterated cellulose solvents 1‐ethyl‐3‐methylimidazolium acetate (EMIM‐OAc‐d14) and 1‐butyl‐3‐methylimidazolium acetate (BMIM‐OAc‐d18) and of 2‐13C‐butyl‐3‐methylimidazolium acetate

The syntheses of two perdeuterated ionic liquids (ILs), which have found use as solvents for cellulose derivatization and processing in addition, are described: 1‐ethyl‐3‐methylimidazolium acetate (EMIM‐OAc‐d₁₄) and 1‐butyl–3‐methylimidazolium acetate (BMIM‐OAc‐d₁₈). The targets were obtained from imidazole in three‐step sequences starting with butylation and ethylation, respectively. The resulting 1‐alkyl imidazoles were purified, and subsequently methylated according to a novel protocol using dimethylcarbonate‐d₆. To obtain the 1‐alkyl‐3‐methylimidazolium moiety, methylation of 1‐alkylimidazoles proved to be superior to the conventional approach of alkylating 1‐methylimidazole. Addition of acetic acid‐d₄ caused traceless degradation of the methylcarbonate counter anions, which were neatly exchanged for acetate. The IL 2‐¹³C‐butyl‐3‐methylimidazolium acetate, in which the isotopically enriched C‐2 is a good NMR‐indicator of side reactions and solvent–solute interactions, was synthesized according to the same reaction sequence, starting from 2‐¹³C‐1‐alkylimidazole which, in turn, was obtained by reaction of glyoxale, alkylamine, ammonia and paraformaldehyde‐¹³C. Copyright © 2009 John Wiley & Sons, Ltd.     

Water and Ethanol Extracts of Piper nigrum in Regulating Thyroid Function and Lipid Peroxidation in Mice

Abstract

An investigation was made to evaluate the effects of water and ethanol extracts of Piper nigrum L. fruits in the alteration of the serum thyroid hormone concentrations and tissue lipid peroxidation in liver, the main target organ of many drugs. The alcohol extract, at a dose of 4.0 mg/kg for 15 days, caused thyrotoxicosis as evidenced by increased concentrations of thyroxine and triiodothyronine. A concomitant increase in hepatic lipid peroxidation with a decrease in superoxide dismutase and/or catalase activities also indicated its peroxidative effect. However, a trial with the aqueous extract did not exhibit any toxic effect either on thyroid or in liver functions. Rather, the latter extract appeared to be antithyroidic and antiperoxidative in nature as it could decrease serum thyroid hormone concentrations and hepatic lipid peroxidation, respectively. It is suggested that the aqueous extract of Piper nigrum may be preferred over the alcohol extract for therapeutic uses.     

Preparation of mucoadhesive oral patches containing tetracycline hydrochloride and carvacrol for treatment of local mouth bacterial infections and candidiasis

The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability.     

微球的制备和表征

目的制备葡激酶突变体(K35R，DGR)的聚乳酸-羟基乙酸(PLGA)微球，使其在包封和释放过程中都能保持活性。方法使用复乳溶剂挥发法制备DGR的PLGA微球，研究了搅拌速度、PLGA浓度、内水相和外水相中的添加剂对蛋白包封率以及微球性质的影响，并进行了DGR微球的体外和体内释放试验。结果2%聚乙烯醇可以有效抑制超声乳化时DGR在水/二氯甲烷界面上的变性，将DGR的活性回收率从16%提高到几乎100%。在外水相中加入NaCl可以显著提高蛋白包封率，同时对微球的粒径分布和表面形态也产生了重要影响。DGR微球的体外释放呈现两个时相，15 d释放大约DGR总活性的50%。DGR微球在体内持续释放5 d。结论制备的PLGA微球，DGR包封率高，稳定性较好，是DGR的良好载药系统。