The stability of ascorbic acid microencapsulated in granules of rice starch and in gum arabic

Ascorbic acid (AA) was microencapsulated by spray drying, using gum arabic and rice starch as covering materials. The AA was dissolved in solutions of the wall material prior to processing. For the rice starch, gelatin was used as a binding agent and recovery was effected with calcium pectate. The morphology of the materials was analysed by optical and scanning electron microscopy, it thus being possible to verify the formation and evaluate the structural characteristics of the microcapsules. The capsules produced with gum arabic were smaller (d50% = 8.0 microns) and with a multimode particle size distribution, whilst uncovered starch capsules containing 1-2% gelatin presented a distribution mainly in the range of 5-40 microns. The capsules recovered with calcium pectate had average diameters 10-15 times greater than those obtained only by spray drying. The stability of the encapsulated materials was studied at room temperature (RH 60-65%) and at 45 degrees C (RH 60-65% and 90.7%). AA microencapsulated in gum arabic was shown to be as stable as free crystalline AA under environmental conditions, whereas that encapsulated in rice starch was less stable. Increasing the amount of the binding agent gelatin increased the stability of the uncovered starch encapsulated AA. Recovery with calcium pectate notably increased the stability of the starch encapsulated AA, as compared to the uncovered samples.     

Microencapsulation of ascorbic acid: effect of process variables on product characteristics

This study deals with a comparative investigation of the characteristics of ascorbic acid microcapsules prepared by different methods, such as thermal phase separation, melt dispersion, solvent evaporation and spray drying. Scanning electron microscopy (SEM), release tests and size distribution were used for the evaluation of product characteristics. The results show that microencapsulated ascorbic acid could prevent the ascorbic acid colour change, retard its core release rate, and generally mask its acid taste. In the thermal phase separation, molecular weight (M_w) of ethyl cellulose (EC) and the addition of polyisobutylene (PIB) significantly influenced the aggregation and release rate of microcapsules. In the melt dispersion method, spherical particles were prepared by using carnauba. The ascorbic acid release rate was found to be slower in the case of carnauba-encapsulated ascorbic acid than that made by EC using other methods. In the solvent evaporation method, a higher M_w of EC and the addition of plastizer were also found to be important for good encapsulation. In the spray drying method, loss of ascorbic acid was found to be minimum during microencapsulation. Starch and beta-cyclodextrin encapsulated ascorbic acid delayed the degradation of ascorbic acid during storage at 38°C and relative humidity 84.0%.     

The microencapsulated ascorbic acid release<Emphasis Type="Italic">in vitro</Emphasis> and its effect on iron bioavailability

The present study was carried out to examine the stability of microencapsulated ascorbic acid in simulated-gastric and intestinal situation in vitro and the effect of microencapsulated ascorbic acid on iron bioavailability. Coating materials used were polyglycerol monostearate (PGMS) and medium-chain triacylglycerol (MCT), and core materials were L-ascorbic acid and ferric ammonium sulfate. When ascorbic acid was microencapsulated by MCT, the release of ascorbic acid was 6.3% at pH 5 and 1.32% at pH 2 in simulated-gastric fluids during 60 min. When ascorbic acid was microencapsulated by PGMS, the more ascorbic acid was released in the range of 9.5 to 16.0%. Comparatively, ascorbic acid release increased significantly as 94.7% and 83.8% coated by MCT and PGMS, respectively, for 60 min incubation in simulated-intestinal fluid. In the subsequent study, we tested whether ascorbic acid enhanced the iron bioavailability or not. In results, serum iron content and transferring saturation increased dramatically when subjects consumed milks containing both encapsulated iron and encapsulated ascorbic acid, compared with those when consumed uncapsulated iron or encapsulated iron without ascorbic acid. Therefore, the present data indicated that microencapsulated ascorbic acid with both PGMS and MCT were effective means for fortifying ascorbic acid into milk and for enhancing the iron bioavailability.     

Protective effect of arabic gum against acetaminophen-induced hepatotoxicity in mice

Overdose of acetaminophen, a widely used analgesic drug, can result in severe hepatotoxicity and is often fatal. This study was undertaken to examine the effects of arabic gum (AG), which is commonly used in processed foods, on acetaminophen-induced hepatotoxicity in mice. Mice were given arabic gum orally (100 g l(-1)) 5 days before a hepatotoxic dose of acetaminophen (500 mg kg(-1)) intraperitoneally. Arabic gum administration dramatically reduced acetaminophen-induced hepatotoxicity as evidenced by reduced serum alanine (ALT) and aspartate aminotransferase (AST) activities. Acetaminophen-induced hepatic lipid peroxidation was reduced significantly by arabic gum pretreatment. The protection offered by arabic gum does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione, because arabic gum did not alter acetaminophen-induced hepatic glutathione depletion. Acetaminophen increased nitric oxide synthesis as measured by serum nitrate plus nitrite at 4 and 6 h after administration and arabic gum pretreatment significantly reduced their formation. In conclusion, arabic gum is effective in protecting mice against acetaminophen-induced hepatotoxicity. This protection may involve the reduction of oxidative stress.     

Development and application of a novel UV method for the analysis of ascorbic acid

A UV method for the analysis of ascorbic acid with methanol as solvent to prepare a sample has been developed and applied. The effect of copper(II) concentrations on the oxidation of ascorbic acid in aqueous solution has been studied in detail, and the regularities of ascorbic acid oxidation in methanol, USP phosphate buffer (pH 2.50) and de-ionized water have been found. Upon experiments ascorbic acid has been found to dissolve in methanol, and its solubility in it has been measured to be 81.0 mg/ml at room temperature (22 °C). The ascorbic acid bulk material from a manufacturer has been assayed to be 89.34% with this method, in good agreement with the assay value (89.58%) from the titration method. The ascorbic acid granule and tablet content uniformity also has been tested using this method. This method is simple, rapid, accurate and reliable, and can be adopted for the routine determination of ascorbic acid in its granule and tablet formulations.     

Study of ascorbic acid interaction with hydroxypropyl-beta-cyclodextrin and triethanolamine, separately and in combination

Complexation between ascorbic acid, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and triethanolamine (TEA), separately and in combination, was studied in solution and solid state. The freeze-drying method was used to prepare solid complexes, while physical mixtures being obtained by simple blending. These complexes were characterized in the solid state using differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Nuclear magnetic resonance spectroscopy ((1)H and (13)C NMR) was used in aqueous solutions to obtain information about the mode of interaction. The degradation rate of each complex in solution was determined, and the stability constant of the complexes and the degradation rate of the ascorbic acid within the complexes were obtained. NMR studies provided clear evidence of partial inclusion into the HP-beta-CD cavity, but the stability constant value was very small indicating a weak host-guest interaction. The influence of complexation on the degradation rate of ascorbic acid was evaluated, and the data obtained showed a pronounced enhancement of aqueous stability with the TEA association complex, while this effect was lower with the HP-beta-CD inclusion complex. NMR experiments showed evidence of the formation of aggregates.     

Microencapsulation of blackberry pulp with arrowroot starch and gum arabic mixture by spray drying

Abstract

This research work aimed to obtain blackberry pulp powder by spray drying and, by an experimental design, evaluated the effect of inlet air temperature (100–150?°C) and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2 on the physicochemical properties of the powders. Arrowroot starch and gum arabic present glass transition temperature (Tg) values above 100?°C; hence it was possible to employ them as carriers in blackberry pulp spray drying in order to increase Tg of the system. Powder yield and solubility increased with increasing blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2, whereas hygroscopicity decreased. Yield, solubility and hygroscopicity of the powders increased and water activity decreased, with increasing inlet air temperature. The powders presented low moisture content and water activity. Temperature of 143?°C and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:1.78 were the optimal conditions to obtain high yield and blackberry powders that are soluble in water and less hygroscopic.     

Some behavioural and EEG effects of ascorbic acid in rats

Ascorbic acid (50–200 mg/kg IP) activated gross behaviour and EEG of rats. The behavioural excitation induced by d-amphetamine (2.5 mg/kg SC) was significantly potentiated by ascorbic acid (100–200 mg/kg IP). Catalepsy induced by haloperidol (0.25 mg/kg IP) was attenuated by ascorbic acid (50–200 mg/kg IP) while pentobarbitone (20 mg/kg IP)-induced sleep in rats was dose-dependently antagonised by ascorbic acid (50–400 mg/kg IP). Ascorbic acid (50–400 mg/kg IP) desynchronized the EEG of the frontal cortex and optic cortex while the EMG activity was slightly enhanced in the rat. Ascorbic acid (100 mg/kg IP) potentiated d-amphetamine (2.5 mg/kg SC)-induced EEG desynchronization and EMG activation in the rat. These results indicate that ascorbic acid exerts stimulatory effects in rats. The results also suggest that dopaminergic mechanism may contribute indirectly or directly to the observed behavioural and EEG effects of ascorbic acid.     

The ambiguous effect of ascorbic acid on chromate induced proteinuria in rats

The influence of ascorbic acid (AA, 5 g/kg body weight) on chromate (Cr, 10 mg/kg) induced proteinuria, which is a sensitive parameter of its nephrotoxicity, was investigated in adult female Wistar rats. The concentrations of Cr and ascorbic acid (AA) were determined in renal tissue. Cr nephrotoxicity is related to its intracellular reduction from Cr(VI) to Cr(III). Proteinuria was completely prevented by enhancement of extracellular reduction of Cr(VI) to Cr(III) followed by rapid renal excretion when Cr and AA were given concomitantly. With an interval up to 1 h between Cr and AA, proteinuria was decreased probably by the radical scavenging function of AA. At an interval of 3 h AA enhanced Cr toxicity by increased intracellular Cr reduction. If the interval was increased to 5 h or if Cr was given 24 h after AA, no influence of AA could be detected. Our results confirm that AA is a very effective reductant of Cr which can influence Cr nephrotoxicity in very high concentrations. It depends on the interval between Cr and AA administration whether or not there is a beneficial effect of AA in Cr nephrotoxicity.     

黄原胶和槐豆胶提高维生素C稳定性研究

目的:研究黄原胶和槐豆胶对维生素C稳定性的作用.方法:比较加入黄原胶和槐豆胶前后维生素C在水中含量的变化规律,进行稳定性的研究.结果:黄原胶能显著提高维生素C的稳定性,黄原胶和槐豆胶混合使用具有更好的效果.结论:黄原胶和槐豆胶的配比使用有利于维生素C的稳定,可作为添加剂运用于食品和药品的生产,提高维生素C的稳定性.     

Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats

Objective:

To investigate the preventive and curative role of ascorbic acid on doxorubicin (dox)-induced myocardial toxicity in rats.

Materials and Methods:

Animals were divided into five groups of six animals each. Group I served as normal control and received saline 5 ml/kg/day intraperitoneal (i.p.) for a period of 15 days. Group II animals received ascorbic acid 20 mg/kg per oral (p.o.) for 15 days as a pretreatment control (PR). Group III animals received dox 2.5 mg/kg body weight (b.w.), i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. Group IV animals received ascorbic acid 20 mg/kg p.o. for 15 days as a pretreatment followed by dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg body weight. Group V animals received dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. followed by ascorbic acid 20 mg/kg p.o for 15 days as post-treatment control (CR). The biochemical parameters such as tissue glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), and enzyme biomarkers such as creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were monitored.

Results:

Pretreatment with ascorbic acid (20 mg/kg p.o.) significantly protected the myocardium from the toxic effect of dox (PR), by increasing the levels of antioxidant enzymes such as GSH, SOD, and CAT toward normal and decreased the levels of MDA, CPK, LDH, AST, and ALT as compared with dox-treated rats. Post-treatment with ascorbic acid to dox-treated group (CR) significantly increased the levels of tissue GSH, SOD, CAT and significantly decreased the level of MDA as compared with dox-treated group. It also reduced the severity of cellular damage of the myocardium as confirmed by histopathology. The restoration of the endogenous antioxidant system clearly depicts that ascorbic acid produced its protective effect by scavenging the reactive oxygen species.

Conclusion:

The results obtained in this study provide evidence for the usefulness of the ascorbic acid as a cardioprotective agent.     

Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress.     

The role of ascorbic acid on the redox status and the concentration of malondialdehyde in streptozotocin-lnduced diabetic Rats

We investigated the role of ascorbic acid on the redox status in streptozotocin-induced diabetic rats. In the plasma of diabetic rats, the ratio of reduced/total ascorbic acid was significantly decreased as compared with normal control. Ascorbic acid supplementation increased the reduced and total ascorbic acid contents as compared with diabetic control. In the rutin-treatment group, reduced and total contents of ascorbic acid were significantly decreased, however, the ratio of reduced/total contents of ascorbic acid had no difference as compared with diabetic rats. In the insulin-treatment group, this ratio is not significantly different as compared with diabetic control. However, in the insulin plus ascorbic acid treatment group, reduced form and the ratio of reduced/total ascorbic acid were significantly increased as compared with diabetic control. In addition, we measured the contents of malondialdehyde (MDA) in the plasma of diabetic rats. The contents of MDA was increased as compared with normal control, however, in insulin-treatment group, the contents of MDA was decreased as compared with diabetic rats. Ascorbic acid had no effects on the increases of MDA in diabetic rats. In conclusion, plasma ascorbic acid level and its reduced/total ratio reflects the status of the oxidative stress in the diabetic rats. Supplement of ascorbic acid did not correct the ratio of the reduced/ total ascorbic acid. However, supplement of insulin and ascorbic acid corrected the ratio of reduced/total ascorbic acid.     

Role of ascorbic acid on mercuric chloride-induced genotoxicity in human blood cultures

Efforts are made to find therapeutic agents capable of minimizing genotoxicity of various natural and man-made compounds. The genotoxicity induced by mercury compounds remains controversial. Therefore we have investigated the genotoxic effect of mercuric chloride (MC; HgCl₂) at three concentrations (1.052, 5.262 and 10.524 μ ) and role of ascorbic acid (vitamin C) at a concentration of 9.734 μ on MC-treated short-term human leucocyte cultures. We assessed the proliferative rate index (PRI), sister chromatid exchange (SCE) and chromosomal aberrations (CAS) in control and MC-treated cultures with and without vitamin C supplementation. The results showed that MC has no effect on cell-cycle kinetics, but the frequency of SCE/cell was significantly higher in a dose-dependent manner than control values. HgCl₂ also significantly induced C-anaphases (abnormal mitosis) in blood cultures. These effects were prevented by the addition of vitamin C to MC-treated cultures. The data indicate the mutagenic activity of MC and the protective role of vitamin C on mercury-induced genotoxicity in human blood cultures is probably due to its strong antioxidant and nucleophilic nature.     

The use of a nonlinear absorption model in the study of ascorbic acid bioavailability in man

A two-compartment disposition model of ascorbic acid (AA) pharmacokinetics with saturable and time-constrained intestinal absorption was developed. The model was fitted to pharmacokinetic data obtained after oral administration to nine healthy volunteers of two effervescent dosage forms differing in AA content: Celaskon 60 mg (CK60) and Celaskon 500 mg (CK500). It was demonstrated that in the case of CK500 less than 30% of the dose was absorbed as compared with CK60. Parameters of the AA nonlinear absorption kinetics were assessed by simultaneous fitting of mean concentration—time data for both doses and placebo. The relatively short duration of absorption found (3.2 h) can explain the failure of past attempts to increase the AA bioavailability using sustained-release dosage forms. Model simulation showed that the ingestion of 60 mg with 3–4 h intervals is optimal for maximal bioavailability of AA.     

Chromium (VI) reducing capacity of ascorbic acid and of human plasma in vitro

In the metabolism of chromium(VI) its reduction in human plasma is of importance; an extracellular reduction of Cr(VI) is regarded as a detoxification step. Ascorbic acid has been suggested to represent the majority of the Cr(VI)-reducing capacity of human plasma. Therefore the kinetics of the reaction of Cr(VI) with ascorbic acid, at biologically realistic concentrations were studied. Ascorbic acid, in 0.2 M HEPES buffer and at concentrations ranging from 14.2 to 113.6 nmol ml⁻¹ (2.5–20.0 μg ml⁻¹), was mixed with Cr(VI) (0.4–1.5 nmol ml⁻¹) and incubated at pH 7.4 and 37° C. In addition, chromate solutions at different concentrations [1.5–100 nmol ml⁻¹ Cr(VI)], were incubated at 37° C with freshly drawn blood. From these incubates, ascorbic acid and its oxidized form, dehydroascorbic acid, were simultaneously analyzed by HPLC and post-column derivatization. Chromate was determined by flow injection analysis. The reaction kinetics of ascorbic acid in HEPES buffer with Cr(VI) is of pseudofirst order at higher concentrations, whilst apparently at lower concentrations kinetics are consistent with an autocatalyzed reaction. Results obtained after spiking human plasma are similar. However, when Cr(VI) was reacted with human plasma, no changes in the intrinsic contents of ascorbic acid of the plasma samples occurred. Also, comparing different plasma samples the intrinsic plasma contents of ascorbic acid and the reduction capacities for Cr(VI) [ranging between 0.48 and 0.63 nmol ml⁻¹ Cr(VI) to be reduced] did not correlate. This shows that the reduction of Cr(VI) in native human plasma is complex and is not only determined by the plasma ascorbic acid levels. This is in contrast to the situation in lung lavage fluids (Suzuki 1988; Suzuki and Fukuda 1990) where the concentrations of ascorbic acid are much higher than in blood.     

Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde

The kinetics of conversion of methenamine to the active form formaldehyde were studied in pooled urine samples at 37° in the pH range 4.9–6.5. Using a method for the determination of both formaldehyde and unhydrolyzed methenamine, the rate of formaldehyde formation in urine was found to be apparent first order and was pH dependent. Bactericidal concentrations of formaldehyde (>28 μg ml^?1) were achieved in 3 h in urine of pH 6.0 containing methenamine at 750 μg ml^?1. There was no difference in the in vitro rate of conversion of methenamine to formaldehyde between the urine collected from normal subjects and the urine from subjects administered ascorbic acid. The rates of degradation of the mandelate and hippurate salts in buffer systems of various pH values did not differ significantly from those of methenamine base in urine adjusted to the same pH. The half-life of methenamine conversion to formaldehyde increased approximately 20 times from 20 h at pH 5.0 to about 400 h at pH 6.5. The data suggest that unless the urine is maintained below pH 6 only a small fraction of methenamine would be converted daily to formaldehyde and, thus, may explain the need for large doses of this drug in patients.     

复方氨基酸注射液残氧量控制与色氨酸稳定性的关系

目的建立复方氨基酸注射液中残氧量的控制参数和方法,降低注射液中色氨酸的氧化降解速率。方法通过优化复方氨基酸注射液生产过程中充氮气装置和控制参数,从而稳定控制药液内的氧含量。结果在180瓶/分的灌装速度时,控制灌装前充气流量13m3.h-1、灌装后充气流量8m3.h-1可将残氧量控制在低于3%的水平。结论残氧量控制在3%左右可有效降低氨基酸注射液中易氧化降解成分色氨酸的氧化降解速率,稳定产品质量。     

病毒消提取条件优选及其颗粒剂的制备

目的：研究病毒消颗粒的提取条件及制备。方法：采用正交设计法优选最佳提取条件,以醇提和水提的主要有效成分为参考指标,选择提取时间,提取次数和溶剂用量3个因素,每个因素取3个水平,按L9(3^4)正交表安排实验,结果：醇提取的最佳提取条件为A3B3C2,即用10倍量95％乙醇回流提取2次,每次3h,水提取的最佳提取条件为A3B2C2,即用8倍量水煎煮3次,每次3h,结论：该工艺简单,可行,收率高。     

铜(Ⅱ)—去甲斑蝥酸络合物存在下抗环血酸对DNA链的断裂作用

本文在pH 7.40,37℃磷酸盐缓冲体系中,研究了铜(Ⅱ)的去甲斑蝥酸络合物(Cu(Ⅱ)/H₂DCA)存在下,不同因素对抗坏血酸(H₂A)断裂DNA链的影响。实验结果表明,Cu(Ⅱ)/H₂DCA催化抗坏血酸有氧氧化过程中产生的H₂O₂进一步发生Fenton反应,生成的·OH是抗坏血酸断裂DNA链的真正物种。但简单的Fenton反应不能解释本实验的所有结果。