Combined use of extended-release niacin and atorvastatin： safety and effects on lipid modification

Background Cholesterol-lowering therapy with statins has been reported to reduce the morbidity and mortality of cardiovascular diseases. This study aimed to investigate the effects of combined application of extended-release niacin and atorvastatin on lipid profile modification and the risks of adverse events in patients with coronary artery disease. Methods Consecutive 108 patients with coronary artery disease and serum total cholesterol （TC） 〉 3.5 mmol/L were randomized into two groups： group A using atorvastatin and group B using extended-release niacin （niacin ER） and atorvastatin. Plasma lipid profile, glucose, and adverse events were assessed at the hospitalization, and 6 and 12 months after treatment. In addition, clinical cardiovascular events were evaluated after 12 months of treatment. Results The levels of TC, low density lipoprotein cholesterol （LDL-C） were significantly decreased （P 〈0.05） in groups A and B, but the levels of high density lipoprotein cholesterol （HDL-C） and ApoA increased by 29.36% and 40.81% respectively after 12 months of treatment in group B （P 〈0.01）. The medications were generally well tolerated in the two groups. No significant difference of adverse events was found between the two groups （group A： 3.2% vs group B 5.1%, P 〉0.05）. Conclusions Combined use of extended-release niacin with atorvastatin was superior to atorvastatin monotherapy alone in lipid profile regulation. Combination therapy with niacin ER and atorvastatin was well tolerated and safe in patients with coronary artery disease.

Evaluation of chitosaneanionic polymers based tablets for extended-release of highly watersoluble drugs

The objective of this study is to develop chitosaneanionic polymers based extendedrelease tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading.Here,the combination of sodium valproate(VPS)and valproic acid(VPA)were chosen as the model drugs.Anionic polymers studied include xanthan gum(XG),carrageenan(CG),sodium carboxymethyl cellulose(CMC-Na)and sodium alginate(SA).The tablets were prepared by wet granulation method.In vitro drug release was carried out under simulated gastrointestinal condition.Drug release mechanism was studied.Compared with single polymers,chitosaneanionic polymers based system caused a further slowdown of drug release rate.Among them,CS exanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h.Differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR)studies demonstrated that polyelectrolyte complexes(PECs)were formed on the tablet surface,which played an important role on retarding erosion and swelling of the matrix in the later stage.In conclusion,this study demonstrated that it is possible to develop highly water-soluble drugs loaded extendedrelease tablets using chitosaneanionic polymers based system.

Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

Evaluation Procedure for Quality Consistency of Generic Nifedipine Extended-Release Tablets Based on the Impurity Profile

A procedure to evaluate the quality consistency of generic drugs based on the impurity profile and the similarity analysis methods was presented in this paper. Nifedipine extended-release tablets from six generic factories of China were used to evaluate the uniformity with the original drug in the study. The procedure includes: choice of chromatographic methods, data collection and conformity test, evaluation of intra-batch similarity of drugs, evaluation of generic drugs with the original drug and weighted similarity evaluation of generic drugs. The data were collected via high-performance liquid chromatography (HPLC), and then calculated by correlation coefficient, cosine, principal component analysis (PCA) and hierarchical clustering analysis (HCA). It is more suitable to use peak areas as the vector when calculating the similarity of impurity profile. After weighting the peak areas of the unspecified impurities in further evaluation of the generic quality, the generic level of different factories was differentiated and the best generic factory was picked out.

Design and evaluation of nicorandil extended-release tablet

The aim of this study was to design and evaluate extended-release formulations of a model drug,nicorandil,in order to achieve the desired steady-state plasma concentration of drug in vivo.Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil.The dissolution test was employed using pH 1.2,4.0,6.8 buffer solution,or water,to measure the in vitro release behaviors of nicorandil formulations.A single dose(15 mg)of each formulation was orally administered to four beagle dogs under fasted conditions,and the pharmacokinetic parameters were calculated.The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs.Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets.The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation.The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extendedrelease formulations.These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

Self-Reported Adherence after Overnight Switching from Immediate- to Extended-Release Pramipexole in Parkinson’s Disease

Background: Drug adherence decreased in patients with Parkinson’ s disease (PD) because of taking many different types of drugs. We evaluated drug adherence after switching from immediate-release (IR) to once-daily extended-release (ER) pramipexole (PPX) in PD. Methods: This study included 35 PD patients (20 men, 15 women);10 were taking oral PPX alone, and 25 were also using another anti-PD drug. PPX-IR was switched overnight to PPX-ER without gradual tapering. One month after switching, improvement in timing adherence and reduction in medication burden were evaluated by a questionnaire using a visual analog scale (VAS) (0: No change;10: Better). Motor function was assessed using part III of the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: The VAS score for improvement in timing adherence was 8.1 ± 0.5 (mean ± standard error), and that for reduction in medication burden was 7.3 ± 0.6. There was a significant negative correlation (ρ = -0.43, p = 0.01) between the VAS score and number of types of medications. The UPDRS part III score improved significantly after switching

Mechanism of Niacin Induced Hot Flushes and Suppression of Cholesterol

Niacin or nicotinic acid is a form of B3 vitamin prescribed at higher concentrations for the suppression of cholesterol levels. Supplemental doses may cause very little or no side effects. However, higher concentrations of niacin cause hot flushes for most people. Here we propose a biochemical mechanism of niacin induced hot flushes. Orally taken prescription doses of niacin are converted to NAD with the liberation of excess pyrophosphate which in turn releases energy in the form of heat (hot flushes through capsaicin receptor) by the action of pyrophosphatases. The excess pyrophosphate may suppress cholesterol biosynthesis through feedback mechanism. The pathways of NAD and cholesterol biosynthesis were discussed with refence to the production and function of pyrophosphate.

陀螺状碳酸钙的“一步法”制备及性能表征

以维生素B_(3)为改性剂,在水溶液体系利用“一步法”制备了陀螺状碳酸钙粒子。采用控制变量法考察了反应温度和改性剂添加量等因素对碳酸钙结晶行为的影响,并确定最佳反应条件。利用SEM、XRD对产物的结构和性能进行表征,并对成核机理进行初步探讨。此方法对碳酸钙的改性研究具备一定指导意义。

基于斑贴及稳定性试验剖析含烟酰胺化妆品皮肤刺激性成因

为探究含烟酰胺化妆品可能引起人体皮肤刺激性反应的主要原因,开展了健康志愿者烟酸、烟酰胺斑贴试验及含烟酰胺化妆品稳定性试验研究。首先选取含烟酰胺化妆品进行斑贴试验,同时测定烟酸、烟酰胺含量水平;随后进行了不同含量烟酸溶液(0.000 5%,0.001%,0.01%,0.025%)和3%烟酰胺溶液斑贴试验,并开展了含烟酰胺化妆品稳定性试验。结果发现:45个含烟酰胺化妆品中,17个会引起皮肤反应(占总数的37.8%),41个检出烟酸(占总数的91.1%),含量为0.000 15%~0.026 6%;采用自建皮肤反应评分方法进行评分,皮肤反应评分总和与烟酸含量正相关具有统计学意义(r=0.406,P=0.006),与烟酰胺含量相关无统计学意义(r=0.099,P=0.517)。0.000 5%烟酸、0.001%烟酸、3%烟酰胺溶液对皮肤刺激性与阴性对照的差异无统计学意义(P>0.05);0.025%烟酸、0.01%烟酸对皮肤刺激性与阴性对照的差异具有统计学意义(P<0.05)。含烟酰胺化妆品在25℃放置8周烟酸含量稳定,在55℃放置8周烟酸含量呈现逐渐增加趋势。

硫辛酸烟酸二联体对蓝光致大鼠视网膜损伤的防治作用

目的:探讨硫辛酸烟酸二联体(N2L)对蓝光致SD大鼠视网膜损伤的防治作用及最佳药物剂量,探寻其可能存在的保护机制。方法:选取150-200 g的SPF级雄性SD大鼠36只,随机分为正常对照组、蓝光损伤组、N2L低剂量组(1.0 mg/kg)、N2L中剂量组(2.5 mg/kg)、N2L高剂量组(5.0 mg/kg)及生理盐水组,每组各6只。正常对照组12 h明暗循环饲养,其余组每日接受9 h日常光照,3 h波长455 nm、强度3000±50 lx蓝光照射及12 h黑夜来建立损伤模型,持续14 d。同时每日腹腔注射1 mL对应剂量的药物。14 d后,所有组常规12 h明暗循环再饲养5 d,采用视网膜电图检查。过量麻醉法处死大鼠制备标本,HE染色,在光学显微镜下观察外核层厚度;CheKineTM超氧化物歧化酶(SOD)活性检测试剂盒检测SOD活性;Western Blot检测大鼠视网膜Caspase-3、醌氧化还原酶1(NQO1)、谷胱甘肽巯基转移酶(GST)、Bcl-2和Bax蛋白表达量。结果:蓝光损伤组暗视ERG 3.0、10.0(cd·s)/m^(2)刺激光下b波、明视ERG 3.0(cd·s)/m^(2)刺激光下b波振幅及震荡电位第2个波峰振幅显著低于正常对照组(均P<0.01),N2L中剂量组较蓝光损伤组振幅显著提高(均P<0.05),且与正常对照组无显著差异;蓝光损伤组较正常对照组视网膜ONL厚度下降(P<0.001),N2L中剂量组厚于蓝光损伤组(P<0.001),与正常对照组无显著差异;N2L中剂量组超氧化物歧化酶活性显著高于其余5组(P<0.05);蓝光损伤组Caspase-3、Bax及NQO1表达量较正常对照组更高(均P<0.01),N2L中剂量组Bax、Caspase-3表达量较蓝光损伤组显著降低(均P<0.001),而GST、NQO1及Bcl-2显著增加(均P<0.01)。结论:2.5 mg/kg N2L能有效拮抗蓝光对SD大鼠视网膜的损伤作用,有望成为其防治药物。

烟酸皮肤潮红反应用于抑郁症诊断的相关研究(综述)

抑郁症是一种以显著而持久的情绪低落、兴趣减退和快感缺失为主要症状的精神疾病;目前,由于抑郁症的高发病率、高自杀率、高复发率,如何准确有效的识别、干预抑郁症引起了重视。烟酸皮肤潮红测试是一种用于评估细胞膜中脂肪酸含量的简单方法;大量研究发现,抑郁症患者存在烟酸皮肤敏感度的显著降低,烟酸皮肤潮红反应钝化有望成为诊断抑郁症的辅助生物标志物。本文通过对国内外相关文献进行分析总结,重点对抑郁症中烟酸皮肤潮红反应的产生机制、检测方法以及研究进展3个方面展开论述,以挖掘该方法在辅助诊断抑郁中的价值,并期待能为今后更加深入的研究提供依据。

Chronic niacin overload may be involved in the increased prevalence of obesity in US children

AIM: To investigate nicotinamide’s action on glucose metabolism, and the association between niacin consumption and obesity prevalence. METHODS: Dynamic nicotinamide’s effect on plasma hydrogen peroxide and glucose metabolism was in- vestigated using oral glucose tolerance tests with or without nicotinamide in the same five healthy subjects.Lag-regression analysis was used to examine the association between the niacin consumption and the obesity prevalence among US children using the data from the Economic Research Service of the US Department of Agriculture and from US Centers for Disease Control and Prevention, respectively. RESULTS: Compared with the control oral glucose tolerance test, the 1-h plasma hydrogen peroxide (1.4 ± 0.1 μmol/L vs 1.6 ± 0.1 μmol/L, P = 0.016) and insulin levels (247.1 ± 129.0 pmol/L vs 452.6 ± 181.8 pmol/L, P = 0.028) were signif icantly higher, and the 3-h blood glucose was signif icantly lower (5.8 ± 1.2 mmol/L vs 4.5 ± 1.1 mmol/L, P = 0.002) after coadministration of glucose and 300 mg nicotinamide. The obesity prevalence among American children increased with the increasing per capita niacin consumption, the increasing grain contribution to niacin due to niacin-fortification, and the increasing niacin-fortified ready-to-eat cereal consumption, with a 10-year lag. The regression analyses showed that the obesity prevalence in the US children of all age groups was determined by niacin consumption (R2 = 0.814, 0.961 and 0.94 for 2-5 years, 6-11 years and 12-19 years age groups, respectively). CONCLUSION: The appetite-stimulating effect of nicotinamide appears to involve oxidative stress. Excess niacin consumption may be a major factor in the increased obesity prevalence in US children.

The biochemical pathways of central nervous system neural degeneration in niacin deficiency

Neural degeneration is a very complicated process. In spite of all the advancements in the molecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is a common sequela of the conditions of niacin deficiency. Neural degeneration in Pellagra manifests as chromatolysis mainly in pyramidal followed by other neurons and glial cells. However, there is a gross lack of understanding of biochemi- cal mechanisms of neurodegeneration in niacin deficiency states. Because of the necessity of niacin or its amide derivative NAD in a number of biochemical pathways, it is understandable that several of these pathways may be involved in the common outcome of neural degener- ation. Here, we highlight five pathways that could be involved in the neuraldegeneration for which evidence has accumulated through several studies. These pathways are： 1） the trypto- phan-kyneurenic acid pathway, 2） the mitochondrial ATP generation related pathways, 3） the poly （ADP-ibose） polymerase （PARP） pathway, 4） the BDNF-TRKB Axis abnormalities, 5） the genetic influences of niacin deficiency.

Effects of Micronutrient Niacin on Treatment Efficiency of Textile Wastewater

Textile wastewater is well known as one of the wastewaters to be most difficultly treated. The effects of niacin on textile wastewater treatment efficiency were studied by continuous addition of 1.0 mg·L^-1 niacin, the physical and chemical indexes of the water samples, such as COD, ammonia and dehydrogenase activities, were analyzed every day with standard methods, and obvious improvement in wastewater treatment performance was achieved. The exact results showed that：① Niacin could improve the COD removal efficiency signifcantly with removal rates being 1.31 times as to those of the control system; ② under this experimental condition, addition of niacin had almost no effect on the removal of ammonia;③ Addition of niacin could improve the activity of dehydrogenase by 130 %. It proved that the biological treatment performance of textile wastewater treatment system probably could be optimized through micronutrient niacin supplement.

Sociodemographic Factors Associated with Dietary Intake of Thiamine, Riboflavin, and Niacin among Chinese Adults in 2015

Objective To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China.Methods We derived our data from the China Health and Nutrition Survey(CHNS) among 12,241 individuals aged 18–64 years. Log binomial regression was used to estimate adjusted prevalence ratios for factors associated with the inadequate intake of B-vitamins.Results Females with low incomes and living in the north had a higher prevalence of inadequate riboflavin intake than those with high incomes and living in the south. Both males and females living in a village had a higher prevalence of inadequate riboflavin intake than adults living in a city. Adults with low income, low education, and living in the north or in a village had a higher prevalence of inadequate niacin intake than adults with a high income, high education, and living in the south or in a city.Conclusion We found that income, region, and area of residence were associated with riboflavin intake. Education, income, region, and area of residence were associated with niacin intake. Welltailored strategies and policies are needed to improve nutritional status in China.

Protective effects of lipoic acid-niacin dimers against blue light-induced oxidative damage to retinal pigment epithelium cells

AIM: To evaluate the protective effects of lipoic acid-niacin(N2 L) dimers against blue light(BL)-induced oxidative damage to human retinal pigment epithelium(hRPE) cells in vitro.METHODS: h RPE cells were divided into a control group(CG), a BL group, an N2 L plus BL irradiation group, an α-lipoic acid(ALA) plus BL group, an ALA-only group, and an N2 L-only group. hRPE cellular viability was detected by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium(MTT) bromide assays, and apoptosis was evaluated by annexin-V-PE/7-AAD staining followed by flow cytometry. Ultrastructural changes in subcellular organelles were observed by transmission electron microscopy. Reactive oxygen species formation was assayed by flow cytometry. The expression levels of the apoptosis-related proteins BCL-2 associated X protein(BAX), B-cell leukmia/lymphoma 2(BCL-2), and caspase-3 were quantified by Western blot analysis.RESULTS: BL exposure with a light density of 4±0.5 mW/cm2 exceeding 6 h caused hRPE toxicity, whereas treatment with a high dose of N2 L(100 mol/L) or ALA(150 mol/L) maintained cell viability at control levels. BL exposure caused vacuole-like degeneration, mitochondrial swelling, and reduced microvillus formation;however, a high dose of N2 L or ALA maintained the ultrastructure of hRPE cells and their organelles. High doses of N2 L and ALA also protected hRPE cells from BL-induced apoptosis, which was confirmed by Western blot analysis: BCL-2 expression significantly increased, while BAX and caspase-3 expression slightly decreased compared to the CG.CONCLUSION: High-dose N2 L treatment(>100 mol/L) can reduce oxidative damage in degenerating hRPE cells exposed to BL with an efficacy similar to ALA.

High dose niacin in the treatment of acne vulgaris:a pilot study

Introduction Acne patients are frequently associated with abnormal lipid profile. It may be useful to apply high doseof niacin that regulates the lipid profile along with acne treatment. There is no report about high dose of niacin in treatment ofacne. Objective To evaluate the therapeutic effect and safety of high-dose niacin in acne vulgaris. Methods Acne patientswere randomly allocated to two treatment groups. Both groups were treated orally with the tablets for 12 weeks; the niacingroup at an increasing dose of niacin tablet: 2000 mg (40 mg/kg/d). The control group (nicotinamide group) at a dose ofnicotinamide tablet: 600 mg (10 mg/kg/d). All patients were asked not to consume certain foods such as milk and alcohol.A high-protein, low-fat and low-glycemic-load diet was recommended in both groups. Results A total of 108 patients werefinished the study. Niacin group: 56 patients; control group: 52 patients. After 12 weeks of treatment, niacin and nicotinamidecaused improvement in acne patients. Percentage Improvement in the niacin group (82.37±7.837) %was significantly higherthan in the nicotinamide group (63.19±10.18)%, P <0.01. The number of successful cases in the niacin group was significantlyhigher than in the nicotinamide group after 12 weeks of treatment, (χ2 = 10.55, P <0.01). Conclusions High dose niacin canreally do it work in treatment of acne vulgaris. The therapeutic effcct of High dose of niacin in treatment of acne vulgaris ismore effective than nicotinamide.

Development and validation of HPTLC method for niacin and simvastatin in binary combination

A simple, sensitive and validated HPTLC method has been developed to determine Niacin and simvastatin simultaneously in synthetic mixture form. Chromatographic separation was achieved on a RP18 plate using a mixture of Methanol: Water: Acetic acid (60:40:0.1) at a wavelength of 237 nm. Linearity of themethod was found to be in the concentration range of 5000.0-25000.0 μg/ml for niacin and 100.0-500.0 μg/ml for simvastatin with correlation coefficient greater than 0.999. The method can be used for simultaneous determination of Niacin and Simvastatin.

Cu-NIC-TMED富集黄芩中黄芩苷的规律及机理

以烟酸(NIC)为配体制备了金属-有机骨架材料(MOFs)铜-烟酸-四甲基乙二胺配位聚合物(Cu-NICTMED),并将其用于黄芩中黄芩苷的吸附、分离和纯化,建立了一种无毒无害、环境友好、流程简化且效率较高的提取方法.采用溶剂热法合成Cu-NIC-TMED,然后对其进行结构表征,以实现适当的配位及准确合成.研究了Cu-NIC-TMED吸附黄芩苷的规律和机理:该吸附符合准二级动力学方程,平衡吸附数据符合Langmuir吸附等温模型.同时,通过对响应面(RSM)进行优化得到最佳吸附参数.在最佳吸附参数条件下,Cu-NIC-TMED对黄芩中黄芩苷的吸附率高达84.08%,且对黄芩中其它成分的吸附效果微乎其微.使用pH=6.8的磷酸盐缓冲溶液(PBS)作为解吸溶液,Cu-NIC-TMED解吸黄芩苷的解吸率为41.24%,黄芩苷的纯度由吸附前的21.55%提高到解吸后的75.77%,Cu-NIC-TMED在吸附前后具有良好的稳定性,回收率达到78.64%.因此,Cu-NIC-TMED在黄芩苷的吸附纯化中具有应用价值.

Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain

Neuroinflammation plays a critical role in the pathological process of multiple neurological disorders and pathological pain conditions.GPR109A,a Gi protein-coupled receptor,has emerged as an important therapeutic target for controlling inflammation in various tissues and organs.In this review,we summarized current data about the role of GPR109A in neuroinflammation.Specifically,we focused on the pharmacological features of GPR109A and signaling pathways used by GPR109A to ameliorate neuroinflammation and symptoms in Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,stroke,and pathological pain conditions.