Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 139
Filter
1.
Acta Pharmaceutica Sinica ; (12): 700-706, 2022.
Article in Chinese | WPRIM | ID: wpr-922885

ABSTRACT

In order to research the mechanism of guiding action of borneol in Suxiaojiuxin pills, the model of in vitro intestinal absorption, in vivo drug metabolism of mice and cell in vitro absorption model of Caco-2 were established firstly. All animal experiments were in accordance with the regulations of the Animal Ethics Committee of Nankai University. The results showed that the cumulative absorption quantity and absorption permeability of ferulic acid and ligustilide in the intestinal juice of Suxiaojiuxin pills group were significantly increased comparing with fake Suxiaojiuxin pills group, which don't contain borneol. By using borneol, the content of ferulic acid and ligustilide in the blood and tissues, such as heart, were added. The transepithelial resistance value and the content of horseradish peroxidase (HRP) in Caco-2 were rapidly decreased and increased, respectively. Due to further explore mechanism of promoting intestinal absorption of borneol for drugs, in this study, photosensitive probes of borneol were synthesized to capture its targets, and dual luciferase reporter system was used to evaluate its activity of calcium. It was found that it could make calcium overload by regulating transient receptor potential cation channel, subfamily M, member 8 (TrpM8). Then, the results of mass spectrometry imaging showed that the accumulation of ferulic acid in the heart was significantly increased by borneol, and the relaxation rate of rat thoracic aorta was enhanced obviously. In summary, the borneol in Suxiaojiuxin pills can expand cell space and increase intestinal permeability by acting on TrpM8, thus promoting the intestinal absorption, tissue distribution and target organ enrichment of drugs.

2.
Braz. J. Pharm. Sci. (Online) ; 58: e18524, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364432

ABSTRACT

Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali


Subject(s)
Animals , Male , Female , Mice , Stomach/drug effects , Stomach Ulcer/pathology , Tissues/drug effects , Tissue Distribution , Astragalus Plant/adverse effects , Plants, Medicinal , Administration, Oral
3.
Article in Chinese | WPRIM | ID: wpr-883513

ABSTRACT

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis,abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects.However,the role of herb-drug interaction between indomethacin and A.officinarum based on pharmacokinetic,tissue distribution and excretion still remains unknown.In this study,an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS)method was developed for simultaneous determina-tion of indomethacin and its three metabolites,O-desmethylindomethacin(ODI),deschlor-obenzoylindomethacin(NDI)and indomethacin acyl-β-D-glucuronide(IDAβG)by oral administration of indomethacin solution with and without the ethanolic extract of A.officinarum and applied to comparative pharmacokinetic,tissue distribution and excretion studies.Our results clarified that oral administration of A.officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin.And the pharmacokinetic interaction between indomethacin and A.officinarum reduced the systemic exposure of indomethacin and increased its elimination.Tissue distribution results demonstrated that co-administration of A.Officinarum could not reduce the accumulation of indo-methacin in the target tissue of the stomach,but could accelerate the excretions of indomethacin and its three metabolites including ODI,NDI and IDAβG in the bile and feces of rats in the excretion study.Therefore,A.Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

5.
Arq. bras. cardiol ; 114(2): 234-242, Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088869

ABSTRACT

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.


Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.


Subject(s)
Animals , Male , DNA Damage/genetics , Heart Failure/genetics , Reference Values , Rats, Wistar , Oxidative Stress , Muscle, Skeletal/pathology , Comet Assay , Single-Cell Analysis , Heart Failure/pathology , Heart Ventricles/pathology , Hemodynamics , Liver/pathology , Lung/pathology , Myocardial Infarction/genetics , Myocardial Infarction/pathology
6.
Article in Chinese | WPRIM | ID: wpr-846264

ABSTRACT

Objective: To establish a sensitive, accurate and reliable LC-MS-MS analysis method for the nine major components (berberine, berberrubine, jatrorrhizine, palmatine, baicalin, wogonin, oroxylin A, geniposide and gardenin B) in Huanglian Jiedu Decoction (HJD) in rat hippocampus, cortex, striatum, and cerebrospinal fluid, and to study the distribution characteristics of the components in brain tissues of rats. Methods: The mass spectrometry detection conditions and chromatographic analysis conditions of nine main components and internal standards (clarithromycin and chloramphenicol) was optimized, and then the methodological investigations were performed. After HJD was administrated for 1 h, the samples of cerebrospinal fluid, hippocampus, cortex and striatum tissues were collected, and the contents of nine components in these samples were measured. Results: Berberine, jatrorrhizine, palmatine, baicalin, wogonin, oroxylin A and gardenin B showed a good linear relationship in the range of 1-250 ng/mL (r2 > 0.99). Berberrubine had a good linear relationship in the range of 1-500 ng/mL (r2 = 0.991 2), and geniposide had a good linear relationship in the range of 5-500 ng/mL, respectively (r2 = 0.999 5). The intra-day and inter-day precision of each component was less than 12.94%, the accuracy was from -12.71% to 6.91%; The extraction recovery rate was from 88.02% to 106.7%; The matrix effect was from 88.92% to 105.10%; And the short-term, freeze-thaw cycle and long-term stability were less than 12.51%. The content of each component in the hippocampus, cortex and striatum was berberine > baicalin > geniposide > berberrubine > palmatine > wogonin > jatrorrhizine > oroxylin A > gardenin B; And the content of each component in cerebrospinal fluid was geniposide > berberine > berberrubine > palmatine > baicalin> gardenin B > jatrorrhizine > wogonin > oroxylin A. Conclusion: The method can be used for the simultaneous detection of the concentration of nine active components in brain tissues of rats, and successfully applied to the study of brain tissue distribution, which provides a reference for HJD to treat brain diseases.

7.
Article in Chinese | WPRIM | ID: wpr-845189

ABSTRACT

Objective: To investigate the pharmacokinetics, tissue distribution and excretion characteristics of Fc- G- CSF (the fusion protein of Fc and granulocyte colony stimulating factor)in rats. Methods: Fc-G-CSF was labeled with 125I by the chloramine T method, and the content of 125I-Fc-G-CSF in each biological sample was determined by the trichloroacetic acid(TCA)precipitation method. Results: After a single subcutaneous injection of 125I-Fc-G-CSF 30 μg/kg, the AUC was(362.1±48.1)μg•h/L and the Cmax was(27.0±3.0)μg/L. Up to 36 hours of the drug administration, the drug exposure was highest in serum but lowest in brain. Up to 96 hours of the drug administration, the cumulative excretion rate through urine was about 57.5%, and the cumulative excretion rate through feces was about 23.5%. Conclusion: The blood concentration of 125I-Fc-G-CSF reached a peak after 12 h of the subcutaneous injection in rats, and the serum concentration was continuously higher than the concentrations in other tissues. The 125I-Fc-G-CSF excretion mainly adopted the urinary excretion.

8.
Article in Chinese | WPRIM | ID: wpr-855759

ABSTRACT

AIM: To establish a HPLC-UV method to determine sunitinib in rat plasma and mouse tissues, and to study its pharmacokinetics in rats and tissue distribution characteristics in mice. METHODS: The biotic samples were prepared by protein precipitation followed by a stereoselective analysis of sunitinib was achieved on Waters XBridgeTM C18 (4.6 mm×250 mm, 5 μm) with a mobile phase composing of methanol-0.02 mol/L sodium dihydrogen phosphate (70:30) at a flow rate of 1.0 mL/min. The detection wavelength was 310 nm, and the column temperature was 25 ℃. RESULTS: The calibration curve for rat plasma sunitinib was linear in the range of 0.019 2-15.34 μg/mL. The linear ranges in mice brain and kidney were 0.038 3-11.50 and 0.038 3-69.00 μg/mL, respectively. After intragastric administration of sunitinib at a dose of 20 mg/kg to rats, the pharmacokinetic characteristics were Tmax=9.0 h, Cmax=0.194 mg/L, t1/2=18.4 h, AUC(0-∞)=6.8 mg•L-1•h. And the absolute bioavailablity was 47.1%. It was indicated that sunitinib could permeate the blood brain barrier, but the concentration was lower in brain and higher in kidney. CONCLUSION: A HPLC-UV method for the determination of sunitinib in rat plasma and mouse tissues was established. The method is simple, rapid, reliable, and provides a reference for the clinical application of sunitinib.

9.
Article in Chinese | WPRIM | ID: wpr-878791

ABSTRACT

In this study, the chemical profiling of Jingyin Granules and the tissue distribution of nine major constituents in this Chinese medicine were performed after oral administration of Jingyin Granules to rats, by using UHPLC-Q-Exactive Orbitrap HR-MS. An Acquity UPLC BEH C_(18) chromatographic column(2.1 mm×100 mm, 1.7 μm) was used as solid phase, while the mobile phase was methanol and 0.1% formic acid water for gradient elution. The major constituents in this Chinese medicine were quickly and accurately identified, via comparison with the retention times and MS/MS spectra of the standards. A total of 106 chemicals were identified from Jingyin Granules, including 24 kinds of organic acids, 47 kinds of flavonoids, 10 kinds of iridoids, and 21 kinds of saponins and 4 kinds of other compounds. After oral administered Jingyin Granules to rats, 48, 30, 25, 23, 45, 34, 39, 26, 19 prototype compounds were identified in serum, heart, liver, spleen, lung, kidney, brain, fat, and testicles, respectively. Meanwhile, an LC-MS based analytical method was established for simultaneous determination of chlorogenic acid, swertiamarin, caffeic acid, sweroside, liquiritin, prim-O-glucosylcimifugin, arctiin, 5-O-methylvisammioside and arctigenin in biological samples. The tissue distribution(serum, liver and lung) of these nine aim constituents in rats after oral administration of Jingyin Granules were investigated. It was found that these nine constituents could be quickly absorbed into circulation system and then distributed to liver and lung tissues. Except arctigenin, the exposure of other eight aim constituents to serum and lung was peaked at 1 h. At 1 h, the exposure of these components to lung tissue were ranked as follows: swertiamarin [(75 191.0±3 483.21) ng·g~(-1)]>arctiin [(2 716.5±36.06) ng·g~(-1)]>5-O-methylvisammioside [(585.1±0.71) ng·g~(-1)]>arctigenin [(437.45±3.18) ng·g~(-1)]>chlorogenic acid [(308.1±5.66) ng·g~(-1)]>prim-O-glucosylcimifugin [(211.35±2.19) ng·g~(-1)]>sweroside [(184.3±9.05) ng·g~(-1)]>caffeic acid [(175.95±2.05) ng·g~(-1)]>liquiritin [(174.78±153.34) ng·g~(-1)]. In summary, an UHPLC-Q-Exactive Orbitrap HR-MS method has been established for rapid and accurate identification of the constituents in Jingyin Granules, while the tissue distribution of nine major absorpted constituents were investigated in rats following oral administration of Jingyin Granules. These findings provided key information and guidance for further studies on pharmacodynamic substances and clinical applications of Jingyin Granules.


Subject(s)
Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Rats , Tandem Mass Spectrometry , Tissue Distribution
10.
Article in Chinese | WPRIM | ID: wpr-827965

ABSTRACT

To explore the pathogenesis of heart and kidney imbalance insomnia and the regulatory effect of Jiaotai Pills, in order to study the changes of central and peripheral neurotransmitters in rat. Insomnia rats with heart and kidney imbalance were induced through intraperitoneal injection with p-chlorophenylalanine(PCPA, 400 mg·kg~(-1)·d~(-1)), and the model rats were intragastrically administrated with Jiaotai Pills(3.3 g·kg~(-1)·d~(-1)) for 7 days. Nine neurotransmitters were determined by UPLC-MS/MS and principal component analysis(PCA) method in serum, urine, brain, heart, liver, kidney and adrenal gland of rats. The results showed that the ratio of 5-HT and 5-HIAA in platelet of insomnia rats was significantly lower than that in the normal group, and Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, the changed neurotransmitters in blood of insomnia rats were 5-HIAA, E, NE, DA, Glu and ACH, and except ACH, the changes of 7 kinds of neurotransmitters in urine were more significant, Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, all of the 8 neurotransmitters in insomnia rats except HVA were changed. Jiaotai Pills could regulate the neurotransmitters in each tissue of insomnia rats, especially in brain, liver and adrenal gland. In conclusion, insomnia is caused by not only a change of neurotransmitters in brain, but also a series of changes in peripheral tissues. It indicates that insomnia is a systematic imbalance of neurotransmitters. Jiaotai Pills not only regulates the central nervous system, but also has a certain protective effect on other organs, reflecting the multi-target and systematic effect of Jiaotai Pills in the treatment of insomnia.


Subject(s)
Animals , Chromatography, Liquid , Drugs, Chinese Herbal , Neurotransmitter Agents , Rats , Sleep Initiation and Maintenance Disorders , Tandem Mass Spectrometry
11.
Rev. bras. farmacogn ; 29(6): 744-748, Nov.-Dec. 2019. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1057858

ABSTRACT

ABSTRACT This study was designed to explore the pharmacokinetic regularity of the plasma concentration, tissue distribution and excretion of orcinol glucoside from aqueous extracts of raw and processed Curculigo orchioides Gaertn., Hypoxidaceae. The experiment first used an ultrahigh-performance liquid chromatography-tandem mass spectrometry approach with multiple reaction monitoring and a positive mode to separate orcinol glucoside from naringin to obtain the plasma concentration curves, bar graph of tissue distribution and excretion curves. These results might be beneficial for reasonable clinical application of C. orchioides and for further development of its wine and salt-processing mechanism.

12.
J Pharm Biomed Sci ; 2019 Jun; 9(6): 62-70
Article | IMSEAR | ID: sea-215726

ABSTRACT

Background Apocynin, a main component extracted from the root of Picrorhiza kurroa Royle, was a well-knownNADPH oxidase inhibitor and reported to have effect on lung injury, liver injury, diabetes and asthma. AN-1, anitrone derivative of apocynin, was found to exhibit significant effect on treatment of acute lung injury.Aim In order to carry out further preclinical study, it is important to reveal in vivo disposition of AN-1. A simple andrapid high-performance liquid chromatography (HPLC) method was developed to disclose the tissue distributionbehavior of AN-1 in Sprague-Dawley (SD) rats.Methods A HPLC method was developed and validated to measure the concentration of AN-1 in tissue sampleswith carbamazepine as internal standard (IS). The mobile phase consisted of water and methanol (47:53, v/v), theflow rate was 1 mL/min, and an ultraviolet (UV) detector was used at wavelength of 279 nm. The tissue distributionstudy of AN-1 was performed in Sprague-Dawley (SD) rats after a single intravenous dose of 40 mg/kg.Results The developed HPLC-UV method was of good specificity, precision (< 4%), accuracy (90-97%) and recovery(88-104%) for analysis of AN-1 in tissue samples of rats. The linear range was established over a concentrationrange 0.2-50 µg/mL (r2 > 0.998) in tissues including heart, liver, spleen, lung, kidney and brain. After administration,AN-1 was rapidly distributed in tissues and reached peak concentration with time, which showed a high distribution

13.
J Pharm Biomed Sci ; 2019 May; 9(5): 48-56
Article | IMSEAR | ID: sea-215709

ABSTRACT

Background Apocynin (4-hydroxy-3-methoxyacetophenone), an important active ingredient contained in root ofPicrorhiza kurroa Royle, has been widely investigated as an antioxidative and anti-inflammatory agent in kinds ofdisease models, and exerted certain efficacy deserving further research. However, little was known about thedisposal process of apocynin in vivo, which is important information required in drug research and development.Aim In this work, a tissue distribution study of apocynin was performed in Sprague-Dawley (SD) male rats to helpfurther understanding well the disposition of apocynin in vivo.Methods A simple HPLC-UV method was developed for measurement of apocynin concentration in rat tissues. Amixture of water-methanol (47:53, v/v) was used as solvent system, the flow rate was 1 mL/min, and the detectedwavelength was 279 nm. The method was validated and applied to the tissue distribution study of a single bolusintravenous administration of apocynin in SD male rats.Results The developed HPLC-UV method showed good specificity, precision, accuracy and extraction recovery. Thegood linearity was achieved within 0.8-32 μg/mL in tissues including heart, liver, spleen, lung, kidney and brain. Thelower limit of quantification (LLOQ) was 0.8 μg/mL. The method was well used in the study of tissue distribution ofapocynin. The results demonstrated that apocynin was distributed fast into the tested tissues and reached peakconcentration at 5 min after injection. Apocynin was mainly distributed in liver, kidney and lung within 15 minutesafter administration, and eliminated from the tissues with no sample be detected more than 2 h after dose

14.
Acta Pharmaceutica Sinica ; (12): 2064-2068, 2019.
Article in Chinese | WPRIM | ID: wpr-780280

ABSTRACT

Vinpocetine (VP) has been widely used to treat cerebrovascular disorders and nerve injury. Borneol (BN), as an important traditional Chinese medicine, is commonly used to promote the absorption and distribution of central nervous system drugs. In this work, a LC-MS/MS method was developed to determine the level of VP in rat plasma and tissues, and to evaluate the effect of co-administration of BN with VP by oral gavage on the absorption and tissue distribution of VP in rats. Rats were divided into VP (10 mg·kg-1), VP (10 mg·kg-1) + BN (75 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for pharmacokinetic study, and divided into VP (10 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for tissue distribution study. The animal experiment was approved by Ethics Committee of Hubei University, and complied with the guideline for caring and using of laboratory animals. Compared to VP group, the AUC0-∞, MRT0-∞ and t1/2z of VP + BN (150 mg·kg-1) group increased significantly, by 1.98-, 1.22- and 1.42-fold respectively, and the exposure in plasma, liver, kidney and brain increased by 2-, 1.5-, 1.5- and 1.3-fold respectively. The pharmacokinetic results suggested that co-administration of BN with VP is beneficial for overcoming the undesirable pharmacokinetic characteristics of VP, such as short residence time, low oral bioavailability and brain exposure in clinical usage.

15.
Acta Pharmaceutica Sinica ; (12): 1179-1189, 2019.
Article in Chinese | WPRIM | ID: wpr-780226

ABSTRACT

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), as a label-free imaging technique with high coverage and sensitivity is widely used for visualizing the spatial distribution of proteins, peptides and small metabolites in tissues. With the development of MALDI technique, MALDI-MSI is also employed to monitor the spatial distribution of phytochemical constituents of medicinal plants. In this review, we first briefly introduce MALDI-MSI technique, and we focus on its application in the spatial distribution and accumulation of secondary metabolites in medicinal plants. The ultimate advantage of using MALDI-MSI for spatial distribution analysis at the molecular level, offers crucial evidence of synthesis, transfer and accumulation of bioactive molecules in medicinal plants.

16.
Article in Chinese | WPRIM | ID: wpr-802433

ABSTRACT

Objective: In this paper,the effect of microemulsion in Chuanqi ophthalmic microemulsion in situ gel was investigated. Method: The effect of microemulsion was confirmed by the parallel comparison between the Chuanqi microemulsion in situ gel and normal in situ gel,including study of pharmaceutical characterization and tissue distribution. Result: The average particle sizes of Chuanqi microemulsion in situ gel and normal in situ gel were (38.20±0.13) nm and (985±37) nm,respectively.Microemulsion could maintain the properties of nanocarrier in a microemulsion in situ gel composite system.The result of tissue distribution study showed that only ligustilide could be detected.This was related to the nature of these three indicator components(ligustrazine,ligustilide and astragaloside A).The common logarithm of oil and water partition coefficient of ligustilide(lgP) was 2.87,which was consistent with the range of lgP of ideal ophthalmic drugs(lgP=2.0-3.0).The ligustilide from Chuanqi microemulsion in situ gel could be detected in the cornea,vitreous body and retina,and this compound from normal in situ gel could only be detected in the cornea with low content.At the same time,microemulsion could increase the content of ligustilide in corneal tissues. Conclusion: The characteristics of microemulsion nanocarriers can increase the solubility of ligustilide,compared with normal in situ gel,it can be better distributed in the tears outside the corneal,it reaches the cornea with a higher concentration,and forms a corneal concentration gradient,and ligustilide is transported from the anterior ocular region to the posterior ocular region through the transocular barrier.

17.
Article in Chinese | WPRIM | ID: wpr-802173

ABSTRACT

Objective:To study on the pharmacokinetics and tissue distribution of baicalin magnesium salt in rats after tail vein injection,and compare pharmacokinetic differences between baicalin magnesium salt and baicalin. Method:After tail vein injection of baicalin magnesium salt and baicalin,orbital blood was collected at different time points.The drug concentration was measured by HPLC,the drug concentration-time curve was plotted,the pharmacokinetic parameters were calculated with DAS 3.0 software,SPSS 19.0 software was used for statistical analysis.At the same time,the drug distribution in heart,liver,spleen,lung and kidney was measured at different time points after tail vein injection of baicalin magnesium salt. Result:When the dose of baicalin magnesium salt was 25-100 mg·kg-1,area under the curve(AUC0-t and AUC0-∞) showed a good linear relationship with the dose(r>0.95),but most of the other pharmacokinetic parameters had no significant difference between different dose groups.The mean residence time(MRT0-t) of medium dose group of baicalin magnesium salt was significantly higher than that of equal molar dose group of baicalin.After intravenous injection of baicalin magnesium salt,the drug concentration was the highest in each tissue at 0.25 h,and the concentration of target component decreased rapidly at 0.75 h.The distribution of target component in kidney was the most,followed by lung. Conclusion:After injection,the baicalin magnesium salt can be rapidly distributed and quickly eliminated in vivo,which is mainly excreted from the kidney.

18.
Article in Chinese | WPRIM | ID: wpr-802172

ABSTRACT

Objective:To investigate the tissue distribution of major bioactive components from Gegen qinlian Tang(GQT) in rats,and to reveal the mechanism for the efficacy of GQT by the tissue targeting of its bioactive ingredients in vivo. Method:After oral administration of GQT in rats,tissues were collected at different time points,including small and large intestine,liver,heart,spleen,lung,and kidney.Samples were prepared for determination of 14 bioactive components of GQT in tissue homogenate by HPLC-MS/MS.The chromatography separation was performed on an Agilent ZORBAX SB-C18 column(2.1 mm×100 mm,3.5 μm) with acetonitrile-0.1% formic acid in water for gradient elution.Electrospray ionization(ESI) was applied and operated in the positive ion mode.Meanwhile,naringin was used as the internal standard for determining. Result:HPLC-MS/MS for simultaneous determination of 14 components from GQT in tissue homogenate was developed and validated by specificity,calibration curves,recovery test,matrix effect,precision,accuracy,and stability.In the small intestine,the the area under the curve(AUC0-10 h) of major isoflavonoids(puerarin,3'-hydroxypuerarin,and daidzein) were 22 174.9,15 893.1,3 882.5 h·mg·L-1,major flavonoids(baicalein,wogonin,wogonoside,and baicalin) were 15 423.6,15 408.4,7 017.3,3 697.7 h·mg·L-1,and major alkaloid(berberine) was 2 544.0 h·mg·L-1,respectively.The distribution of these ingredients in the small intestine was significantly higher than that in other tissues. Conclusion:The effective ingredients of GQT are mainly distributed in the intestinal tissues,which speculates that the anti-inflammatory and antidiarrheal activities of GQT may be related to its targeting in the intestine.

19.
Article in Chinese | WPRIM | ID: wpr-802078

ABSTRACT

Objective: To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles. Method: The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established,when dosage of administration in tail vein was 20 mg·kg-1,and then the effect of free drug(DTX),non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated. Result: The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC,the linearity,precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study,the plasma concentration of PBAE-DTX was always at a high level within 24 h.Compared with PELA-DTX and DTX,the areas under the curve(AUC0-∞) of PBAE-DTX were increased by 3.63% and 8.96%,the mean residence times(MRT) were extended by 2.86% and 6.43%,the half-life and the drug blood circulation time were prolonged.In the tissue distribution study,it was found that three docetaxel preparations were distributed in the heart,liver,spleen,lung,kidney and tumor tissue within 1 h after administration,but the distribution of these drugs in the tissues was reduced along with the extension of time,the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h. Conclusion: PBAE-DTX can prolong the circulation time of docetaxel in the blood,increase its bioavailability,and significantly increase its distribution in tumor tissue.

20.
Chinese Pharmacological Bulletin ; (12): 883-888, 2019.
Article in Chinese | WPRIM | ID: wpr-857244

ABSTRACT

Aim: To establish an LC-MS/MS method to simultaneously determinate strychnine (STR), brucine (BRU), strychnine N-oxide(SNO) and brucine N-oxide(BNO) in rat tissue, and study their tissue distributions following single intragastric administration of total alkaloids from Semen Strychni at normal and high toxic dose. Methods: Ephedrine hydrochloride was used as the internal standard (IS). Analytes were extracted from tissue samples using liquid-liquid extraction with chloroform. Chromatographic separations were performed on a ZORBAX E-clipse XDB-C18 column(2.1 x 150 mm, 3. 5 μm) with the mobile phase of phase A(water, 10 mM ammonium acetate, adjusted to pH 4. 0 with formic acid) and B(methanol) at a flow rate of 0. 2 mL · min-1. The column temperature was maintained at 30 °C. Mass spectrometric detection was performed on an API4000+ triple quadrupole mass spectrometer equipped with an electrospray ionization (ESI) interface in the positive ion multiple reaction monitoring(MRM) mode. Results: Excellent linearity was observed in all analytes within their linear ranges. In-tra-and inter-day relative standard deviations (RSDs) were less than 14.90%, and accuracies were (85.94 ±1.43)% -(113. 77 ±5.19)%. STR, BRU and SNO distributed in all the tissues in different degree, among which content in kidney and liver was the richest. STR and BRU distributions were low in brain. Conclusions: The developed method is simple, sensitive, specific and reliable, which is suitable for simultaneous determination of STR, BRU, SNO and BNO in rat tissues.

SELECTION OF CITATIONS
SEARCH DETAIL