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Objective:To investigate the effects of different doses of simvastatin and atorvastatin combined with trimetazidine on blood lipids and cardiac function in patients with chronic heart failure.Methods:A total of 100 patients with chronic heart failure who received treatment in Jinan Second People's Hospital from September 2019 to August 2021 were included in this study. These patients were divided into three groups according to different treatment methods: group A ( n = 33), group B ( n = 33), and group C ( n = 34). Group A was treated with a conventional dose of simvastatin combined with trimetazidine. Group B was treated with a high dose of simvastatin combined with trimetazidine. Group C was treated with atorvastatin combined with trimetazidine. All patients were treated for 6 months. Cardiac function, blood lipids, inflammatory factors, and excellent and good rates of therapeutic effects post-treatment were compared between the three groups. The adverse events during the treatment were recorded. Results:There were no significant differences in blood lipids, cardiac function, inflammatory factors, and excellent and good rates of therapeutic effects between the two groups (all P > 0.05). After 6 months of treatment, high-density lipoprotein cholesterol [(1.99 ± 0.25) mmol/L, (2.01 ± 0.16) mmol/L] and left ventricular ejection fraction [(51.29 ± 4.15)%, (51.37 ± 4.44)%] in groups B and C were significantly higher than those in group A [(1.52 ± 0.16) mmol/L, (42.28 ± 4.86)%, t = 9.10, 6.24; 8.10, 11.38, all P < 0.05). Caspase-1 [(42.33 ± 3.19) ng/L, (41.87 ± 3.55) ng/L], interleukin-18 [(54.55 ± 4.39) ng/L, (53.98 ± 4.45) ng/L], left ventricular end-systolic diameter [(35.13 ± 2.13) mm, (35.68 ± 2.46) mm], left ventricular end-diastolic diameter [(44.39 ± 3.65) mm, (44.42 ± 3.32) mm], low-density lipoprotein cholesterol [(2.69 ± 0.39) mmol/L, (2.57 ± 0.13) mmol/L], total cholesterol [(3.79 ± 0.13 ) mmol/L, (3.56 ± 0.69) mmol/L], triacylglycerol [(1.12 ± 0.05) mmol/L, (1.10 ± 0.07) mmol/L] levels in groups B and C were significantly lower than those in group A [(68.41 ±10.23) ng/L, (88.37 ± 6.65) ng/L, (42.63 ± 3.13) mm, (51.68 ± 5.42) mm, (3.13 ± 0.11) mmol/L, (4.21 ± 0.11) mmol/L, (1.51 ± 0.11) mmol/L, t = -13.98, -24.38, -14.27, -24.95, -6.41, -5.64, -8.00, -10.12, -14.17, -18.54, -12.53, -19.01, -5.35, -18.26, all P < 0.05]. 6-minute walking distances [(352.19 ± 25.4) m, (351.74 ± 24.29) m] in groups B and C were significantly longer than that in group A [(319.71 ± 21.11) m, t = 6.63, 5.75, both P < 0.05). The excellent and good rates at 3 and 6 months after surgery in group B was significantly higher than that in group A ( χ2 = 4.00, 4.16, both P < 0.05), but the incidence of adverse reactions in group B [18.18% (6/33)] was significantly higher than 3.03% (1/33) in group A and 2.94% (1/34) in group C (both P < 0.05). There was no significant difference in the incidence of adverse reactions between group A and group C ( P > 0.05). Conclusion:Atorvastatin and high-dose simvastatin alone combined with trimetazidine can achieve good therapeutic effects on chronic heart failure. Both combined therapies are beneficial to improve heart function and reduce myocardial damage. However, atorvastatin combined with trimetazidine is safer than high-dose simvastatin combined with trimetazidine.
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OBJECTIVE To establish a method for simultaneous determination of atorvastatin （ATV） and its active metabolites 2-hydroxy atorvastatin acid （2-HAT）， 4-hydroxy atorvastatin acid （4-HAT） and toxic metabolite atorvastatin lactone （ALT） in rat plasma and apply it for pharmacokinetic study. METHODS LC-MS/MS method was adopted for analysis. The one-step precipitation method was used for processing plasma samples （plasma samples were pretreated by acidification to adjust pH value so as to prevent inversion of configuration）， gradient elution was used to analyze the samples， and the analysis time was 5 min. Electrospray positive ionization was adopted， and positive ion scanning was performed in multi-reaction monitoring. The m/z of quantified ion pairs of ATV and its metabolites such as 2-HAT， 4-HAT and ATL， and internal standard pitavastatin were 559.3→ 440.2， 575.2→440.3， 575.0→440.2， 540.9→448.2 and 422.2→290.0， respectively. After conducting a comprehensive methodological investigation of the analytical method， the concentrations of ATV and its metabolites 2-HAT， 4-HAT，and ATL were determined， and the pharmacokinetic parameters of ATV and its metabolites were calculated using the non- compartment model of WinNonlin 6.1. RESULTS The results of methodological validation showed that endogenous substances in blank plasma did not interfere with the determination of the components to be tested， and the standard curve had a good linear relationship； the lower limits of quantification for ATV， 2-HAT， 4-HAT and ATL were 0.5， 0.5， 0.25 and 0.063 nmol/L， respectively. The precision， accuracy， recovery， matrix effect and stability investigation were all in line with the requirements of biological analysis. Pharmacokinetic analysis showed that after intragastric administration in rats， ATV calcium metabolized rapidly， and was mainly exposed to blood circulation in the form of ATV and 2-HAT， with the lowest concentration of lactone-type metabolites. CONCLUSIONS The established method is precise， rapid and accurate for plasma concentration analysis of ATV and its active/toxic metabolites. The application of the method could help to fully elucidate the pharmacokinetic characteristics of atorvastatin calcium in rats.
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Abstract Objective To investigate the effects of atorvastatin calcium on pulmonary vascular remodeling, the authors explored the regulatory mechanism of Histone Deacetylation Enzyme-2 (HDAC2) in rats with Chronic Obstructive Pulmonary Disease (COPD), and provided a new direction for drug treatment in the progression of vascular remodeling. Methods Eighteen female SD rats were randomly divided into control (Group S1), COPD (Group S2), and atorvastatin calcium + COPD (Group S3) groups. A COPD rat model was established by passive smoking and intratracheal injection of Lipopolysaccharide (LPS). Haematoxylin and eosin staining and Victoria Blue + Van Gibson staining were used to observe pathological changes in the lung tissue. The pulmonary vascular inflammation score was calculated, and the degree of pulmonary vascular remodeling was evaluated. The ratio of Muscular Arteries in lung tissue (MA%), the ratio of the vessel Wall Area to the vessel total area (WA%), and the ratio of the vessel Wall Thickness to the vascular outer diameter (WT%) were measured using imaging software. The expression of HDAC2 was measured using western blotting, ELISA (Enzyme-Linked Immunosorbent Assay), and qPCR (Real-time PCR). Results Compared with the control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in rats with COPD. The WT%, WA%, and lung inflammation scores increased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissue decreased, and the level of Vascular Endothelial Growth Factor (VEGF) in the lung tissues increased (p< 0.05). Compared with the COPD group, the lung tissues from rats in the atorvastatin group had fewer inflammatory cells, and the vascular pathological changes were significantly relieved. The WT%, WA%, and lung inflammation scores decreased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissues increased, and the level of VEGF in the lung tissues decreased (p< 0.05). Conclusion The present study revealed that atorvastatin calcium could regulate the contents and expression of HDAC2 in serum and lung tissues and inhibit the production of VEGF, thereby regulating pulmonary vascular remodeling in a rat model with COPD.
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Objective:To investigate the effect of atorvastatin preconditioning on intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) signaling pathway.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), I/R group, atorvastatin preconditioning group (A group), atorvastatin plus PI3K inhibitor LY294002 group (AL group). Atorvastatin 10 mg/kg was given by intragastric gavage for 3 consecutive days in A and AL groups, and in addition LY294002 0.3 mg/kg was intraperitoneally injected at 30 min before the last administration of atorvastatin in AL group.Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 45 min followed by 2 h reperfusion in anesthetized mice.The superior mesenteric artery was only isolated but not clamped in S group.The mice were sacrificed at the end of reperfusion, and small intestinal tissues were taken for determination of the pathological changes with a light microscope after HE staining and for determination of wet to dry weight ratio(W/D ratio) and expression of PI3K, phosphorylated Akt (p-Akt), autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3Ⅰ (LC3Ⅰ) and LC3Ⅱ.The intestinal damage was assessed and scored according to Chiu.The ratio of LC3Ⅱ expression to LC3Ⅰ expression (LC3Ⅱ/LC3Ⅰ) was calculated. Results:Compared with S group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in I/R, A and AL groups ( P<0.05). Compared with I/R group, Chiu′s scores and W/D ratio were significantly decreased, the expression of PI3K and p-Akt was up-regulated, the expression of Beclin-1 was down-regulated, and LC3Ⅱ/LC3Ⅰ ratio was decreased in A group ( P<0.05). Compared with A group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in AL group ( P<0.05). Conclusion:Atorvastatin preconditioning can mitigate intestinal I/R injury in mice, and the mechanism is related to activating PI3K/Akt signaling pathway and inhibiting the level of autophagy.
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BACKGROUND: Statins plays a significant role in regulating blood lipids, treating and preventing cardiovascular and cerebrovascular diseases. Studies have shown that statins has certain potential in promoting bone formation and treating osteoporosis. OBJECTIVE: To prepare the drug release scaffolds for the sustained release of atorvastatin calcium, which consist of bovine serum albumin microspheres and polycaprolactone electrostatic spinning fibers, and to investigate the effects of the drug sustained release scaffolds on osteoblast adhesion and proliferation. METHODS: Bovine serum albumin microspheres containing atorvastatin calcium were prepared by desolvation. A layer of chitosan was coated on the surface of the bovine serum albumin microspheres by electrostatic adsorption, which can increase the stability of the microspheres. Bovine serum albumin microspheres were purified and lyophilized for later use. The lyophilized powder of microspheres was dissolved in organic solvent. An appropriate amount of hydroxyapatite was added in the solvent. The nanofiber scaffolds for sustained release of atorvastatin calcium were prepared via electrospinning. The micromorphology, degradation performance, and sustained-release performance of the nanofiber scaffolds were characterized. The prepared nanofiber scaffolds for sustained-release of atorvastatin calcium were co-cultured with MC3T3-E1 cells to observe cell adhesion and proliferation. RESULTS AND CONCLUSION: (1) Transmission electron microscopy revealed that the shape of the bovine serum albumin nanospheres was regular and circular. Bovine serum albumin nanospheres were discarded in the electrostatic spinning fibers. The basic morphology of the microspheres was retained. (2) Scanning electron microscopy revealed that the nanofibers used for preparation of nanofiber scaffolds for sustained-release of atorvastatin calcium were composed of filaments with uniform diameters and continuous smooth surface. Filaments were intertwined to form a network structure. (3) The nanofiber scaffolds exhibited the fastest degradation in the first month. The material was incomplete when degraded for 3 months. (4) The nanofiber scaffolds had the ability to slow down the release of drugs. The effect could last for more than 1 month. The overall process of drug release was similar to the zero-order kinetic process. (5) The nanofiber scaffolds for sustained-release of atorvastatin calcium can promote MC3T3-E1 cell adhesion and proliferation. (6) These results suggest that the nanofiber scaffolds for sustained-release of atorvastatin calcium have good biocompatibility and can promote the adhesion and proliferation of osteoblasts.
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Objective:To observe the clinical efficacy of Zhibitai capsule in the treatment of dyslipidemia with phlegm-stasis binding pattern, in order to evaluate its effectiveness and safety. Method:Totally 82 patients of dyslipidemia with phlegm-stasis binding pattern were selected from the outpatient department of internal medicine in Hospital of Xidian University from July 2018 to July 2019. According to the random number table method, they were divided into control group and observation group, with41 cases in each group. Control group was treated with aAtorvastatin calcium, and observation group was treated with Zhibitai capsules. The changes in blood lipid index, liver function and renal function were measured before and after 8-week treatment in two groups, the efficacy on traditional Chinese medicine (TCM) syndromes and clinical symptom scores before and after treatment were compared between two groups, and the adverse reactions, such as liver pain and muscle pain, were recorded among patients. Result:The changes of blood lipids were compared after 8 weeks of treatment, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were all lower than before, while high-density lipoprotein cholesterol (HDL-C) was increased (P<0.05), the total effective rate in control group was 90.24% (37/41), which was 92.68% (38/41) in observation group, with no significant difference between two groups, in the TCM syndrome scores of two groups before and after treatment, four common TCM syndromes, namely scores dizziness, chest tightness, head heavy as if swathed and chest fullness, were decreased (P<0.05). In terms of the efficacy of two groups of TCM syndromes, the total effective rate in control group was 87.80% (36/41), which was 92.68% (38/41) in observation group, with no statistically significant difference between two groups. Control group had 3 cases of increased transaminase, but none of them beyond 2 times of the normal upper limit, and observation group had 1 case of mild abdominal distension and nausea, which did not affect continued medication. No muscle pain or liver pain occurred in two groups. Conclusion:Zhibitai capsule is effective in treating dyslipidemia, which is comparable to atorvastatin calcium in treating dyslipidemia, with the safety and reliability.
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The objective of this study is to isolation and characterization of unknown degradation product of Atorvastatin calcium in combination formulation product with Ezetimibe by using modern techniques of separation and characterization. An unknown impurity is generating during a forced degradation study of Atorvastatin and Ezetimibe fixed-dose combination tablets. By using the gradient reversed-phase high-pressure liquid chromatographic method, unknown degradation impurity was detected and quantified in the range of 0.05% to 0.2% of Atorvastatin. The impurity was enriched by extreme oxidation degradation of Atorvastatin and isolated through preparative HPLC. The structure of the impurity was characterized by mass and NMR spectrum.
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OBJECTIVE： To study the improvement effects of Atorvastatin calcium tablets on renal injury in nephrotic syndrome model rats， and to explore its possible mechanism. METHODS： Wistar rats were randomly divided into normal group， model group and Atorvastatin calcium tablets group， with 10 rats in each group. Model group and Atorvastatin calcium tablets group rats were given adriamycin 6 mg/kg intravenously for consecutive 21 d to induce nephrotic syndrome model. Since 22th day， Atorvastatin calcium tablets group was given drug 8 mg/kg intragastrically while normal group and model group rats were given equal amount of distilled water intragastrically， once a day， consecutive 6 days every week， for consecutive 10 weeks. At the second day after last medication， the plasma levels of albumin （ALB）， total protein （TP）， cholesterol （CH）， urine albumin excretion rate （UAE） were determined in each group. RP-PCR and Western blot assay were used to detect mRNA and protein expression of AMP-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and nuclear factor κB （NF-κB） in liver tissue. RESULTS： Compared with normal group， the levels of ALB and TP， mRNA and protein expression of AMPK and SIRT1 were decreased significantly in model group （P＜0.01 or P＜0.001）， while the levels of CH and UAE， mRNA and protein expression of NF-κB were increased significantly （P＜0.05 or P＜0.01 or P＜0.001）. Compared with model group， the levels of ALB and TP， mRNA and protein expression of AMPK and SIRT1 were increased significantly in Atorvastatin calcium tablets group （P＜0.05 or P＜0.01 or P＜0.001）， while the levels of CH and UAE， mRNA and protein expression of NF-κB were decreased significantly （P＜0.05 or P＜0.01 or P＜0.001）. CONCLUSIONS： Atorvastatin calcium tablets has significant improvement effect on the renal injury of nephritic syndrome model rats， the mechanism of which may be associated with up-regulating the expression of AMPK and SIRT1 and down-regulating the expression of NF-κB.
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O presente estudo teve por finalidade desenvolver uma metodologia de dissolução discriminativa para avaliar comprimidos contendo diferentes polimorfos de atorvastatina cálcica (ATR). Este trabalho é conformado por quatro capítulos, no qual o primeiro apresenta uma breve revisão de literatura sobre as características dos polimorfos da ATR, abordando-se informações mais relevantes sobre o ATR em relação ao polimorfismo e sua influência na biodisponibilidade. No segundo capítulo, apresenta-se a importância da caracterização dos polimorfismos e suas implicações para a ATR. As amostras de ATR foram identificadas por difração raio X e análise térmica e, posteriormente, demonstrou-se as diferenças entre quatro amostras comercializadas no mercado brasileiro relacionadas ao hábito cristalino, tamanho de partícula e solubilidade. No terceiro capítulo, demonstra-se o desenvolvimento do método de dissolução discriminativo para comprimidos contendo duas formas polimórficas da ATR. Para tanto, avaliou-se a solubilidade destas pelo método do equilíbrio e determinou-se as condições experimentais mais adequadas para o ensaio de dissolução por intermédio de planejamento fatorial completo do tipo 23, sendo as variáveis independentes o meio de dissolução, a velocidade de agitação e as formas polimórficas (I e VIII). Os resultados obtidos foram tratados estatisticamente através da análise de variância, dos gráficos de Pareto e de superfície de resposta. Concluiu-se que a velocidade de agitação e o meio de dissolução impactam os resultados, afetando a dissolução das formulações com os polimorfos avaliados. Assim, as condições selecionadas foram: 750 mL de meio água a 65 rpm. Após o desenvolvimento do método, este foi comparado com o da Food and Drug Administration (FDA) para comprimidos de atorvastatina cálcica. Ao final dos ensaios, o método desenvolvido mostrou-se adequado para apontar diferenças entre os polimorfos da ATR. No quarto capítulo, o método desenvolvido foi utilizado para avaliar o perfil de dissolução de comprimidos comercializados em três países sul-americanos: Brasil, Peru e Bolívia. As porcentagens de fármaco dissolvidas e a Eficiência de Dissolução foram as variáveis estudadas e, posteriormente, tratadas estatisticamente através da análise de componentes principais, sendo possível comparar o perfil de dissolução de dessete formulações. Dessa forma, foi possível concluir que cinco formulações avaliadas (BR1, BR2 PE6, BR7 e BO3) possuíam a forma polimórfica VIII, enquanto duas formulações (BR5 e PE2) continham a forma polimórfica I. As demais, possivelmente, apresentam misturas ou outras formas polimórficas
This present study was aimed at developing a discriminative dissolution methodology to evaluate tablets containing different calcium atorvastatin (ATR) polymorphs. This paper consists of four chapters. The first chapter presents a brief literature review of the characteristics of ATR polymorphs, and addresses more relevant information about ATR in relation to polymorphism and its influence on bioavailability. The second chapter presents the importance of the characterization of polymorphs and their implications for ATR. The ATR samples were identified by X-ray diffraction and thermal analysis. Subsequently, the differences among the four samples marketed in the Brazilian market with relation to crystalline habit, particle size and solubility were demonstrated. The third chapter demonstrates the development of the discriminative dissolution method for tablets containing two polymorphic forms of ATR. For this, their solubilities were evaluated by the equilibrium method and the most suitable experimental conditions for the dissolution test were determined by means of complete factorial design of type 23, and the independent variables were the dissolution medium, the stirring speed and polymorphic forms (I and VIII). The results obtained were statistically treated through analysis of variance, Pareto and response surface graphs. It was concluded that the stirring speed and the dissolution medium influenced the results, affecting the dissolution of the formulations with the evaluated polymorphs. Thus, the selected condition was 750 mL of water at 65 rpm. Following the development of the method, it was compared with that of the Food and Drug Administration (FDA) for atorvastatin calcium tablets. At the end of the tests, the developed method was adequate to point out differences between the ATR polymorphs. In the fourth chapter, the developed method was used to evaluate the dissolution profile of tablets marketed in three South American countries: Brazil, Peru and Bolivia. Dissolved drug percentages and Dissolution Efficiency were the studied variables and statistically treated by principal component analysis. Through this method, it was possible to compare the dissolution profile of seventeen formulations. Thus, it was possible to conclude that five formulations evaluated (BR1, BR2, PE6, PE7 e BO3) had the polymorphic form VIII, while two formulations (BR5 e PE2) contained the polymorphic form I. The others possibly have mixtures or other forms polymorphic
Subject(s)
Peru/ethnology , Tablets/analysis , Bolivia/ethnology , Brazil/ethnology , Dissolution/methods , Atorvastatin/analysis , Polymorphism, Genetic , Pharmaceutical TradeABSTRACT
Objective To investigate the clinical effect of endovascular stent implantation and medical treatment in the treatment of symptomatic vertebral artery stenosis. Methods Eighty patients with symptomatic vertebral artery stenosis admitted from January 2013 to May 2015 in the Department of Neurology of Wuhan Puren Hospital were selected. The patients were randomly divided into the observation group and the control group,with 40 cases in each group. The control group was given aspirin enteric?coated tablets 100 mg/ time,1 time /d,clopidogrel bisulfate bablets 75 mg/ time,1 time /d,atorvastatin calcium 10 mg/ time,1 time/d. The observation group was treated with intravascular stent implantation. After 1 years of follow?up, the degree of vascular stenosis,the occurrence of ischemic cerebrovascular time and the clinical effect of the two groups were compared. Results (1) The stenosis degree of the observation group and the control group before treatment was (72. 81±11. 99)％ and (68. 31±12. 35)％ respectively,after treatment,it was (24. 58±1. 24)％ and (56. 01 ±3. 30)％ respectively. There was no significant difference between the two groups before treatment (t=0. 121,P>0. 05). After treatment,vascular stenosis degree in two groups were significantly improved,compared with that before treatment,the differences were statistically significant (t=0. 790,P<0. 05; t=0. 457,P<0. 05); the degree of vascular stenosis after treatment in the observation group was significantly lower than that in the control group ( t=0. 842,P<0. 05);( 2) during follow?up,the total occurrence rate of ischemic cerebrovascular events in the observation group was 17. 5％ (7/40),compared to 37. 5％ (15/40) in the control group,the difference between the two groups was statistically significant (χ2=4. 065,P<0. 05) . ( 3) At 1 years of follow?up,the total effective rate of the observation group was 97. 5％ ( 39/40) ,while that of the control group was 60％ ( 24/40) , and the difference between the two groups was statistically significant ( P=0. 017) . Conclusion Endovascular stent implantation can effectively improve the clinical efficacy of symptomatic vertebral artery, reduce the incidence of ischemic cerebrovascular time,and improve the degree of vascular stenosis.
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Objective To analyze the clinical efficacy of amlodipine atorvastatin calcium tablets in the treatment of hypertension with coronary heart disease .Methods 88 patients with hypertension and coronary heart disease were selected as observation subjects and were randomly divided into control group (44 cases) and treatment group (44 cases) using the digital table method .The control group was treated with atorvastatin ,while the treatment group was treated with amlodipine and atorvastatin calcium .The therapeutic effects of the two groups were compared .Results The total effective rate was 93.18％in the treatment group,which was significantly higher than 75.00％ in the control group (χ2 =5.44,P<0.05).The incidence rate of adverse reactions in the treatment group was 11.36％,compared with 6.82％in the control group,the difference was not statistically significant (χ2 =0.55,P>0.05).Conclusion For patients with hypertension and coronary heart disease ,taking amlodipine atorvastatin calcium treatment can effectively improve their blood pressure conditions .Its efficacy is better than that of atorvastatin ,which is safe and reliable .
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OBJECTIVE: To develop a supercritical fluid chromatography method for the separation of atorvastatin calcium and its enantiomer, meanwhile assaying the enantiomer. METHODS: Atorvastatin calcium and its enantiomer were separated on a ACQUITY UPC2 Trefoil CEL2 column(3.0 mm×150 mm, 2.5 μm) maintained at 45 ℃ with the mobile phase containing a mixture of CO2 and methanol with 0.1% TFA(78∶22, V/V) at 1.5 mL·min-1, and the detection wavelength was set at 244 nm. The back pressure was set at 13.8 MPa. RESULTS: The enantiomer and atorvastatin calcium were separated successfully in 5 min with a resolution factor of 4.1. Good linear relationship was established between the peak response and the concentration in the range of 2.5-50 μg·mL-1 for enantiomer(r2=0.999 9, n=6), the quantitative limit(S/N=10) was 2.5 μg·mL-1, and the detection limit(S/N=3) was 1.0 μg·mL-1. The spiked recovery of the enantiomer was 100.40%(n=9). CONCLUSION: The proposed method shows high accuracy, repeatability and stability. It can be employed for the quality control and stability research of the enantiomer of atorvastatin calcium.
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<p><b>OBJECTIVE</b>To observe the effect of electroacupuncture (EA) on the expressions of CD36 gene and protein in peritoneal macrophages of atherosclerotic rabbits, and to explore the mechanism of acupuncture regulation of atherosclerosis.</p><p><b>METHODS</b>A total of 26 male New Zealand rabbits were randomly divided into a blank group (7 rabbits) and a model group (19 rabbits). The rabbits in the blank group were fed with common feedstuff, and those in the model group were applied with high fat diet and arteria carotis communis bullon injury. One rabbit was sacrificed after 8 weeks to observe the morphological changes of carotid atherosclerotic plaques by HE staining to verify model establishment separately in the blank group and model group. The model rabbits were randomized into a control group, an EA group and a western medication group, 6 rabbits in each one. Common feedstuff was used in the blank group and high fat feed in the other groups. No intervention except grabbing and fixation as the EA group was in the blank group and control group. Rabbits in the EA group were treated with acupuncture at bilateral "Neiguan" (PC 6), "Zusanli" (ST 36), "Guanyuan" (CV 4), and EA with sparse-dense wave was connected at bilateral "Neiguan" (PC 6) and "Zusanli" (ST 36) for 20 min, 4 Hz/20 Hz and 1 mA. 20 mL suspension of 1mg/kg/d atorvastatin calcium tablets were prescribed by intragastric administration in the western medication group for 4 courses, 6 d as one course with 1 d between two courses, once a day. The expression of CD36 protein in peritoneal macrophages was detected by Western blot. Reverse transcription (RT) of RNA and polymerase chain reaction (PCR) of cDNA were used to detect the expression of CD36 mRNA in peritoneal macrophages.</p><p><b>RESULTS</b>In the blank group, the vascular wall thickness was uniform and the endothelium was intact. There was no accumulation of foam cells and atherosclerotic plaques. In the model group, the intima of the artery obviously thickened; the intima was damaged; the atherosclerotic plaque and inflammatory cell infiltration were found in the intima, and the foam cells were seen. After treatment, the expressions of CD36 protein and CD36 mRNA in the control group, EA group and western medication group were higher than those in the blank group (all<0.01). Those in the EA group and western medication group were lower than the expressions in the control group (all<0.01). There was no statistical significance for the expressions of CD36 protein and CD36 mRNA between the EA group and the western medication group (both>0.05). .</p><p><b>CONCLUSION</b>EA can reduce the expressions of CD36 protein and CD36 mRNA in peritoneal macrophages of atherosclerotic rabbits, which may be one of the mechanisms of EA treatment of atherosclerosis.</p>
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Reports indicate that statins (cholesterol-lowering drugs), in addition to lowering cholesterol, have an immunomodulatory effect. This effect may be beneficial for the treatment of several diseases, including periodontal disease. The aim of the present study was to evaluate the immunomodulatory effect of an atorvastatin-medicated dentifrice on CD4+ T cell proliferation. CD4+ T cell proliferation assays and peripheral blood mononuclear cell (PBMC) viability assays were conducted on PBMCs from healthy donors cultured under the following conditions: control, atorvastatin solution, atorvastatin-medicated dentifrice, and dentifrice without atorvastatin at concentrations of 1, 5, 10, 50 and 100 µM. A Generalized Equation Estimation (GEE) model was used to analyze concentration versus proliferation and concentration versus percentage of dead cells within each group evaluated. Atorvastatin-medicated dentifrice (p-value <0.0001) and atorvastatin solution (p-value <0.0001) significantly inhibited CD4+ T cell proliferation in a dose-dependent manner compared with the dentifrice without atorvastatin and control conditions. Only the relationship between atorvastatin solution and percentage of dead cells was significant compared to the other conditions (p-value 0.019). The results revealed that atorvastatin-medicated dentifrice at concentrations of 1 to 100 µM had immunomodulatory effects, inhibiting CD4+ T cell proliferation without affecting PBMC viability. The other components of the dentifrice did not affect CD4+ T cell proliferation or cell viability, indicating its utility as a vehicle to achieve the desired effects of atorvastatin in periodontal tissue. Controlled clinical trials are still needed to evaluate the clinical effects of an atorvastatin-medicated dentifrice on the periodontium.
La literatura indica que las estatinas (medicamentos para bajar el colesterol), además de reducir el colesterol, tienen un efecto inmunomodulador. Este efecto puede ser beneficioso para el tratamiento de varias enfermedades, incluyendo la enfermedad periodontal. El objetivo de este estudio es evaluar el efecto inmunomodulador de una pasta dental medicada con atorvastatina sobre la proliferación celular de linfocitos T CD4+. A partir de células mononucleares de sangre periférica de donantes sanos (PBMC), se realizaron ensayos de proliferación y viabilidad de linfocitos T CD4+ bajo las siguientes condiciones: control, solución de atorvastatina, dentífrico medicado con atorvastatina y dentífrico sin atorvastatina, en concentraciones 1, 5, 10, 50 and 100 µM. Se realizó el análisis estadístico utilizando el modelo Generalized Equation Estimation (GEE) a fin de analizar la concentración versus la proliferación y la concentración versus el porcentaje de muerte celular para cada uno de los grupos. El dentífrico medicado con atorvastatina (valor p <0,0001) y solución de atorvastatina (valor p <0,0001) inhibieron significativamente la proliferación de células T CD4 + de una manera dependiente de la dosis en comparación con el dentífrico sin atorvastatina y condiciones de control. Sólo la relación entre la atorvastatina solución y el porcentaje de células muertas fue significativa en comparación con las otras condiciones (vale-p 0,019). Los resultados revelaron que el dentífrico medicado con atorvastatina en concentraciones de 1 a 100 mM tenía efectos inmunomoduladores, inhibiendo la proliferación de células T CD4 + sin afectar la viabilidad de PBMC. Los otros componentes del dentífrico no afectaron la proliferación de células T CD4 + o la viabilidad celular, indicando su utilidad como vehículo para conseguir los efectos deseados de atorvastatina en el tejido periodontal. Todavía se necesitan ensayos clínicos controlados para evaluar los efectos clínicos de un dentífrico medicado con atorvastatina sobre el periodonto.
Subject(s)
Periodontium/drug effects , CD4-Positive T-Lymphocytes/drug effects , Dentifrices , Atorvastatin/administration & dosage , In Vitro Techniques , CD4-Positive T-Lymphocytes/immunology , Cell Survival/drug effects , Pilot Projects , Cell Proliferation/drug effects , Flow CytometryABSTRACT
BACKGROUND: Although the beneficial effects of statin treatment in dyslipidemia and atherosclerosis have been well studied, there is limited information regarding the renal effects of statins in diabetic nephropathy. We aimed to investigate whether, and which, statins affected renal function in Asian patients with diabetes. METHODS: We enrolled 484 patients with diabetes who received statin treatment for more than 12 months. We included patients treated with moderate-intensity dose statin treatment (atorvastatin 10 to 20 mg/day or rosuvastatin 5 to 10 mg/day). The primary outcome was a change in estimated glomerular filtration rate (eGFR) during the 12-month statin treatment, and rapid renal decline was defined as a >3% reduction in eGFR in a 1-year period. RESULTS: In both statin treatment groups, patients showed improved serum lipid levels and significantly reduced eGFRs (from 80.3 to 78.8 mL/min/1.73 m² for atorvastatin [P=0.012], from 79.1 to 76.1 mL/min/1.73 m² for rosuvastatin [P=0.001]). A more rapid eGFR decline was observed in the rosuvastatin group than in the atorvastatin group (48.7% vs. 38.6%, P=0.029). Multiple logistic regression analyses demonstrated more rapid renal function loss in the rosuvastatin group than in the atorvastatin group after adjustment for other confounding factors (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.42). CONCLUSION: These results suggest that a moderate-intensity dose of atorvastatin has fewer detrimental effects on renal function than that of rosuvastatin.
Subject(s)
Humans , Asian People , Atherosclerosis , Atorvastatin , Diabetes Mellitus , Diabetic Nephropathies , Dyslipidemias , Glomerular Filtration Rate , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Logistic Models , Renal Insufficiency, Chronic , Rosuvastatin CalciumABSTRACT
Objective To investigate the feasibility of a novel molecular probe 99Tcm-3P4-RGD2 in evaluating arterial plaque stability after atorvastatin intervention in rabbits with SPECT/CT. Methods Eighteen male New Zealand rabbits were randomly divided into group A (stable plaque), group B (vulnerable plaque), and group C (vulnerable plaque with statin intervention). All rabbits were fed with high-fat food for 12 weeks. After high-fat feeding for two weeks, sham surgery was performed on group A. In the meantime, abdominal aorta injury was performed on group B and group C. After that, rabbits of group C were given oral atorvastatin (2.5 mg·kg-1·d-1). 99Tcm-3P4-RGD2 SPECT/CT imaging was performed on each group at the end of 4, 8 and 12 weeks. T/NT ratios were calculated. Animals were sacrificed at the end of 12 week after imaging studies. The abdominal aortas were collected, imaged with SPECT/CT, and evaluated by pathological HE staining and immunohistochemical analysis. MVD was calculated. Differences among 3 groups were analyzed using one-way analysis of variance. Results There was no significant radioactive uptake in the abdominal aortas of three groups on the 4th week′s imaging. The radioactive uptake in abdominal aortas increased slightly on the 8th week, with the highest radioactive uptake in group B. The radioactivity in abdominal aortas of the 3 groups maintained increasing on the 12th week, with T/NT ratios of 1.579±0.217, 1.873±0.226 and 1.524±0.237, respectively (F=8.984, P<0.05). In ex vivo abdominal aorta images, especially images of group B, radioactivity in lesion sites was higher than that in normal tissue. Accordingly, results of HE staining showed that artery plaques of group A and group C were grade Ⅱ and group B was grade Ⅳ. The MVD of group A, B and C was 8.17±1.17, 15.86±1.07 and 7.17±1.60, respectively (F=9036, P<0.05). Conclusion 99Tcm-3P4-RGD2 SPECT/CT imaging has a high sensitivity in the evaluation of arterial plaque stability after statin intervention in rabbits.
ABSTRACT
Objective:To prepare the self-microemulsifying drug delivery system (SMEDDS) and relevant tablets of atorvastatin calcium and ezetimibe(Ato-Eze),and investigate the in vitro release of Ato-Eze SMEDDS tablets. Methods:The solubility and excip-ient compatibility of Ato and Eze in different excipients were investigated. The pseudo-ternary phase diagram composed of different oil phase,emulsifier and co-emulsifier was used to obtain the self-emulsifying area. The morphology,particle size distribution and zeta po-tential of microemulsion were determined by a dilution method. The optimal formula of Ato-Eze SMEDDS was prepared into tablets. The drug release profiles of the commercial formula,Ato-Eze SMEDDS and Ato-Eze SMEDDS tablets were compared. Results:The op-timal formula was as follows:propylene glycol monocaprylate as the oil phase,Solutol HS 15 as the surfactant and polyethylene glycol 600 as the co-surfactant with the best ratio of 5 :3.75:1.25. Ato-Eze SMEDDS was a clear and transparent microemulsion solution with homogeneous small spheres as seen under a transmission electron microscope. The particle size and zeta potential of Ato-Eze SMEDDS was(44.2 ± 19.5) nm and( -24.1 ± 1.3) mV,respectively. The in vitro release profile indicated that the accumulated re-lease of Ato-Eze SNEDDS and the tablets reached up to nearly 100% in 45 min. Conclusion: Ato-Eze SMEDDS tablets can signifi-cantly improve the in vitro dissolution rates of the two drugs,and the preparation process is simple and feasible.
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Objective To investigate the effects of atorvastatin and clopidogrel on coronary artery disease.Methods From August 2013 to January 2017,122 patients of acute coronary syndrome in our hospital for diagnosis and treatment were selected as the research object,all the patients were divided into observation group and control group of 61 case accorded to the random lottery envelopes randomly,two groups were treated with percutaneous coronary artery interventional therapy,the control group was given clopidogrel bisulfate adjuvant therapy,the observation group was given atorvastatin atorvastatin calcium and clopidogrel adjuvant therapy,all patients were observed for 4 weeks.Results The total effective rate of the observation group was significantly higher than that of the control group (P ＜ 0.05).The LVEDD and LVESD values of the observation group and the control group after treatment were significantly lower than those before treatment (P ＜ 0.05),while the LVEDD and LVESD values in the observation group were significantly lower than those in the control group (P ＜ 0.05).The platelet membrane glycoprotein GP Ⅱb/Ⅲa values in the observation group and the control group atter treatment were (10.22 ± 3.12)％ and (14.32 ± 2.98)％ that were significantly lower than those before treatment of (20.98 ± 3.30)％ and (21.22 ± 2.98)％,the observation group was significantly lower than the control group (P ＜ 0.05).All patients were followed up for 6 months,the incidence of arrhythmia,bleeding and death in the observation group was 3.3％,so that was 19.7％ in the control group,and the observation group was less than that of the control group (P ＜ 0.05).Conclusion Atorvastatin atorvastatin calcium and clopidogrel adjuvant in patients with acute coronary syndrome therapy can improve heart function,reduce the expression ofplatelet membrane glycoprotein GP Ⅱb/Ⅲa,so as to improve the short-term and long-term efficacy.
ABSTRACT
Objective: To develop and optimize a self-microemulsifying drug delivery system (SMEDDS) formula for improving the dissolution of atorvastatin calcium.Methods: Solubility and pseudo-ternary phase diagram were used to select the suitable type and amount range of oil phase, surfactant and co-surfactant.D-optimal mixture design was used to optimize the formula of atorvastatin calcium SMEDDS.The morphology, particle size distribution and zeta potential of the microemulsion were determined by a dilution method.The in vitro drug release profiles of the marketed atorvastatin calcium tablets and the self-made SMEDDS were compared.Results: The formula of atorvastatin calcium SMEDDS was as follows: Capmul MCM as the oil phase, Labrasol as the surfactant and Transcutol P as the co-surfactant with the optimal weight ratio of 13.0∶43.5∶43.5.The self-made SMEDDS was a clear and transparent microemulsion solution with homogeneous small spheres as seen under a transmission electron microscope.The particle size, PdI and zeta potential of the self-made SMEDDS was (34.2±13.6) nm, (0.169±0.04) and (-21.1±1.3) mV, respectively.The in vitro release profile indicated that the accumulated release of the self-made SNEDDS reached up to nearly 100% in 45 min.Conclusion: The optimal formula of atorvastatin calcium SMEDDS optimized by D-optimal mixture design can improve the drug dissolution rate effectively.
ABSTRACT
Objective To improve the clinical efficacy of angina pectoris with dyslipidemia patients, analysis of the combined use of trimetazidine, atorvastatin calcium, the clinical value of psychological intervention.Methods 86 cases of patients with coronary heart disease and angina pectoris with dyslipidemia were selected, according to the random number table method is divided into control group and study group, each group of 43 cases. The control group were given routine symptomatic angina pectoris of coronary heart disease with abnormal blood lipid therapy plus trimetazidine hydrochloride oral Sibutramine, study group on the basis of the control group given oral atorvastatin calcium plus psychological intervention of statin treatment. Results After treatment, the clinical efficiency of the study group and the control group was 95.34％ and 81.4％, the difference between the two groups was statistically significant (P<0.05); patients in the study group SDS, SAS score than the control group, the difference between the two groups was statistically significant (P<0.05); patients in the study group, TC, TG, LDL and C levels were significantly lower than the control group, the HDL level of C higher than that of control group, the difference between the two groups was statistically significant (P<0.05); study on patients with angina pectoris attack times less than the control group, the seizure duration shorter than the control group, the difference between the two groups was statistically significant (P<0.05). Conclusion Psychological intervention combined with the treatment of angina pectoris of coronary heart disease with abnormal blood lipid, clinical efficiency increased from 81.4％ to 95.34％, reduced in patients with depression, anxiety and other negative emotions, so that the blood has been effectively controlled, improve clinical symptoms, reduce the pain of patients, with high clinical value.