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1.
China Pharmacy ; (12): 635-640, 2022.
Article in Chinese | WPRIM | ID: wpr-920737

ABSTRACT

Caspofungin is the firs t echinocandin antifungal drug approved for serious fungal infections caused by Candida or Aspergillus. Currently ,caspofungin has been recommended as the first-line treatment for invasive Candida and the second-line treatment for invasive Aspergillus,for its safety and tolerability. However ,there are still probability of pharmacokinetic variability and the risk of low exposure in different populations. Herein the population pharmacokinetics-pharmacodynamics studies of caspofungin in children and adults were reviewed. The results indicate that the body surface area was the main factor affecting the distribution and clearance of caspofungin in pediatric patients. In adults ,the two-compartment model fits the caspofungin behavior best in vivo with the primary covariates of body weight and albumin level. The efficacy of caspofungin might be related to pharmacokinetics-pharmacodynamics parameters ,such as the ratio of area under blood concentration time curve to minimum inhibitory concentration (AUC/MIC),the ratio of peak concentration to minimum effective concentration (cmax/MEC).

2.
China Pharmacy ; (12): 699-705, 2022.
Article in Chinese | WPRIM | ID: wpr-923005

ABSTRACT

OBJECTIVE To study th e pharmacodynamics and pha rmacokinetics of Qinglian ningxin capsule in rats with ischemic arrhythmia. METHODS Totally 30 male SD rats were randomly divided into blank control group ,model control group , Qinglian ningxin capsule group (4.00 g/kg),Artemisia annua group(1.43 g/kg),Coptis chinensis group(0.42 g/kg),with 6 rats in each group. Administration groups were given relevant medicine intragastrically ;model control group and blank control group were given normal saline intragastrically ,once a day ,for consecutive 7 days. After last medication ,except for blank control group,other groups were given Posterior pituitary injection via tail vein (1 u/kg) to induce ischemic arrhythmia model. electrocardiogram changes of rats in each group were recorded. Another 36 rats were randomly divided into Qinglian ningxin capsule model group and Qinglian ningxin capsule control group (4.00 g/kg),A. annua model group and A. annua control group (1.43 g/kg),C. chinensis model group and C. chinensis control group (0.42 g/kg). After the rats in each model group were injected with Posterior pituitary injection (1 u/kg)via tail vein ,administration groups were given relevant drugs intragastrically , and control groups were given constant volume of normal saline intragastrically. Blood was taken from the orbit at different time points(0,0.25,0.75,1,2,4,6,8,12 and 24 h). The concentrations of berberine hydrochloride and artemisinin in plasma were determined by HPLC ,and the pharmacokinetic parameters were calculated by WinNonlin 7.0 software. RESULTS Compared with the model control groups ,Qinglian ningxin capsule could significantly improve the heart rate slowing of rats and redu ced the prolongation of PR interval and QT interval significantly ,and the effects were generally better than those of A. annua group and C. chinensis group(P<0.05). Compared with A. annua control group and C. chinensis control group ,cmax,AUC0-t and AUC 0-∞ of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule control group,while CL was decreased significantly ;t1/2z of artemisinin was prolonged significantly (P<0.05). Compared with Qinglian ningxin capsule control group ,cmax(except artemisinin ),AUC0-t,AUC0-∞,MRT0-t and MRT 0-∞(except artemisinin )of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule model group ,while CL was decreased significantly(P<0.05). CONCLUSIONS Qinglian ningxin capsule could significantly improve ischemic arrhythmia better than A. annua and C. chinensis ,and can improve the absorption of berberine hydrochloride and artemisinin in model rats and slow down their elimination.

3.
Article in Chinese | WPRIM | ID: wpr-921756

ABSTRACT

Effective drugs for chronic obstructive pulmonary disease(COPD), a complex chronic lung disease, have long been difficultly determined, while traditional Chinese medicine(TCM) has played a critical effect in the treatment of such disease. A new approach for the prediction based on data analysis by integrating TCM basic theories and modern science is urgently needed apart from clinical experiments. In this study, an efficacy evaluation system of COPD was established based on the multi-target efficacy evaluation system of Chinese medicine to analyze the medication regularity and characteristics, such as efficacies, properties, meridian tropism,and core combinations of Chinese medicines. The characteristics of classical prescriptions in the intervention of COPD were explored from modern pharmacology. The results showed that the Chinese medicines in the classical prescriptions in the treatment of COPD were dominated by heat-clearing, phlegm-resolving, dampness-dispelling, exterior-releasing, deficiency-tonifying, and interior-warming drugs. Among them, dampness-dispelling, interior-warming, and heat-clearing drugs resulted in higher perturbation efficiency in the disease network than some western medicines on the market, suggesting that these drugs possessed better efficacies in the treatment of COPD. In the classic prescriptions, warm-heat drugs were equivalent to cold-cool drugs in number, while the proportion of warm-heat drugs gradually raised with the increase in the perturbation efficiency. Additionally, core combinations in the classical prescriptions,such as heat-clearing/heat-clearing, dampness-dispelling/dampness-dispelling, and phlegm-resolving/heat-clearing, could achieve better efficacy for COPD. The present study preliminarily screened out the efficacies of Chinese medicines in the treatment of COPD based on scientific data through the multi-target efficacy evaluation system to explore the effect of Chinese medicine on COPD from modern pharmacology, explain the mechanism of TCM treatment of lung diseases, and provide references for the development of drugs targeting COPD.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional , Meridians , Prescriptions , Pulmonary Disease, Chronic Obstructive/drug therapy
4.
Article in Chinese | WPRIM | ID: wpr-921628

ABSTRACT

The pharmacology of Chinese medicine is an academic discipline that studies the interaction between Chinese medicine and organism(including pathogens) by modern science and technology under the guidance of traditional Chinese medicine(TCM) theories. However, the pharmacology of Chinese medicine is mainly guided by the theories, techniques, and methods of modern medicine in the development, and TCM theories have been ignored to a certain extent, which does not conform to the action characteristics of Chinese medicine in essence. Since systematic research ideas, strategies, methods, and technologies that conform to the characteristics of TCM have not been established, it is unable to reveal the scientific connotation of TCM in the prevention and treatment of diseases. Therefore, according to the trend of the modern development of TCM and the research status of pharmacology of Chinese medicine, this study put forward the concept of pharmacology of combination of disease and syndrome and expounded the relevant background, content, methods, and significance of this concept. It is expected to improve the standardization of pharmacology of combination of disease and syndrome, guide the safe medication, provide new references for the scientific development of pharmacology of Chinese medicine, and promote the development of the modernization of Chinese medicine.


Subject(s)
Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Social Change , Syndrome
5.
Article in Chinese | WPRIM | ID: wpr-911732

ABSTRACT

Objective:To investigate the efficacy and nephrotoxicity of high-dosepolymyxin B (PMB) in treatment of patients with multidrug-resistant Gram-negative bacteria (MDR-GNB) infections.Methods:Clinical data of 90 patients with MDR-GNB infections who admitted to the Affiliated Huaian First People′s Hospital from January 2018 to December 2020 were retrospectively analyzed. Thirty one patients receivedhigh-dose PMB(≥25 000 U·kg?1·d?1) for treatment (high-dose group) and 59 patients received standard-dose PMB(<25 000 U·kg?1·d?1) for treatment (control group). The curative effect and renal function of the two groups were compared. The factors related toacute kidney injury (AKI) were analyzed with logistic regression.Results:The daily PMB dose and treatment course in high-dose group were (29 800±4 500) U/kg and (9.16±4.15) d, while those of the control group were (17 300±3 500)U/kg and (7.32±3.87) d ( P<0.01). The effective rate of the high-dose group was higher than that of control group (83.9% vs. 61.0%, χ2=4.95, P<0.05).The creatinine levels in high-dose group were increased significantly from 69.40(47.00, 94.70)μmol/L before treatment to 116.20(59.20, 213.20)μmol/L after treatment ( Z=-2.99, P<0.01); while there were no significant changesin control group before and after treatment [55.00(37.00, 92.47)μmol/L vs. 50.10(34.00, 156.00)μmol/L, Z=-1.78, P=0.78]. The 30-day mortality rate in the high-dose group was 32.3% (10/31), that in the standard-dose group was 49.2% (29/59)(χ2=2.36, P=0.12). The AKI incidence rate in high-dose group was higher than that in standard-dose group [ 67.7% (21/31) vs. 45.8% (27/59), χ2=3.94, P=0.04]. There were 4 and 10 deaths due to AKI in the high-dose and standard-dose groups, respectively (χ2=0.25, P=0.61). Logistic regression analysis showed that daily high-dose PMB was independently associated with AKI( OR=2.662, 95% CI:1.082-6.549, P=0.03). Conclusion:Thehigh-dose PMB is effective in treatment of patients with multidrug-resistant Gram-negative bacteriainfections, but the incidence of AKI is also significantly increased. Therefore, when using daily high-dose PMB, the pros and cons must be weighed to avoid increasing the risk of AKI.

6.
Acta Pharmaceutica Sinica ; (12): 3431-3440, 2021.
Article in Chinese | WPRIM | ID: wpr-906818

ABSTRACT

In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.

7.
Article in Chinese | WPRIM | ID: wpr-906530

ABSTRACT

Rheumatoid arthritis (RA) is a common immune-mediated inflammatory autoimmunity disease. Due to its clinical characteristics, RA is classified into the category of "Bi syndrome" in traditional Chinese medicine. Huangqi Guizhi Wuwutang (HGW), originated from Synopsis of Golden Chamber Jinkui Yaolue, is composed of Astragali Radix, Cinnamomi Ramulus, Paeonial actiflora, Zingiberis Rhizoma Recens, and Jujubae Fructus. It has been used for treatment of blood "Bi syndrome" in clinical practice, and nowadays, it is also widely used for treatment of RA or RA with wind-cold-dampness Bi syndrome or Qi and blood deficiency Bi syndrome. In 2018, HGW was collected in the Catalogue of Ancient Classical Prescriptions (the First Batch). In order to provide insight for standardized clinical medication and lay a solid foundation for its further development, we herein reviewed literatures of clinical and animal studies on HGW treatment in RA. According to the basic pathogenesis of RA, HGW can be used for treatment of general RA, RA with wind-cold-dampness Bi syndrome or Qi and blood deficiency Bi syndrome alone or in combination with other drugs. The mechanisms of HGW were related to inhibition of inflammatory cytokines expression, inhibition of lipid peroxidation of synovium, and promotion of apoptosis. However, many issues in the current research still needed to be addressed, such as lack of standardization of drug compatibility and dosage, lack of standardization of clinical trial scheme,undefined drug interaction and unclear safety on the combination of Chinese medicine with chemistry drugs, lack of proper syndrome animal model, and limited study about molecular mechanisms. We propose that future research should focus on the standardization of the clinical trial scheme and RA syndrome of HGW, clarify the principle of drug compatibility and dosage, drug interaction and safety. In terms of mechanistic study, the research should focus on animal models of RA syndrome using multiple dimensions such as genetics, transcription, and metabolism.

8.
Article in Chinese | WPRIM | ID: wpr-906241

ABSTRACT

Objective:To evaluate the analgesic effects of Wenjing Zhitong prescription (WZP) and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine. Method:Analgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E<sub>1</sub> (PGE<sub>1</sub>), respectively in mice. Effect of WZP on uterine contraction frequency, amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits <italic>in vivo</italic>. In the oxytocin-induced rat writhing models, the content of prostaglandin F<sub>2</sub><italic><sub>α </sub></italic>(PGF<sub>2</sub><italic><sub>α</sub></italic>) and prostaglandin E<sub>2 </sub>(PGE<sub>2</sub>) in rat uterine tissues and the content of beta-endorphins (<italic>β</italic>-EP) in rat serum were detected by enzyme-linked immunosorbent assay (ELISA). Expression of estrogen receptor (ER) and oxytocin receptor (OTR) in rat uterine were tested by Real-time polymerase chain reaction(Real-time PCR) method to investigate the possible molecular mechanism of WZP for its analgesic effect. Result:Results of analgesic effect showed that in oxytocin-induced rat writhing experiment, the number of writhing responses in both the WZP (1.5,3.0 g·kg<sup>-1</sup>) group was lower than than in the model group (<italic>P</italic><0.05). In acetic acid-induced mice writhing experiment, the latency of writhing response in WZP (6.0 g·kg<sup>-1</sup>) group was significantly prolonged as compared with that in model group <italic>(P</italic><0.01), and the number of writhing response was significantly reduced (<italic>P</italic><0.05). In PGE<sub>1</sub>-induced mice writhing model, the writhing number in WZP (1.5,3.0,6.0 g·kg<sup>-1</sup>) groups was significantly lower than that in the model group (<italic>P</italic><0.05,<italic>P</italic><0.01). Results of effect on uterine smooth muscle demonstrated that WZP (0.38,0.75,1.50 g·kg<sup>-1</sup>) could significantly reduce the frequency of uterine smooth muscle contraction in rabbits (<italic>P</italic><0.05,<italic>P</italic><0.01), WZP (0.75,1.50,3.00 g·kg<sup>-1</sup>) could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats (<italic>P</italic><0.05). Results of molecular mechanisms of analgesic effects showed that the WZP (0.75,1.50,3.00 g·kg<sup>-1</sup>) significantly reduced the content of PGF<sub>2</sub><italic><sub>α</sub></italic> and the ratio of PGF<sub>2</sub><italic><sub>α</sub></italic> to PGE<sub>2</sub> in the uterine tissue of rats (<italic>P</italic><0.01). In the WZP (3.00 g·kg<sup>-1</sup>) group, the levels of <italic>β</italic>-EP in the serum of rats were significantly increased (<italic>P</italic><0.01), and the levels of OTR in uterus of rats in the WZP (1.50,3.00 g·kg<sup>-1</sup>) group were significantly decreased (<italic>P</italic><0.05). Conclusion:Pharmacological studies demonstrated potent analgesic effect of WZP, and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle, decreasing the contents of PGF<sub>2</sub><italic><sub>α</sub> </italic>and ratio of PGF<sub>2</sub><italic><sub>α</sub></italic>/PGE<sub>2</sub>, reducing OTR expression in uterine as well as increasing the amount of <italic>β</italic>-EP in serum.

9.
China Pharmacy ; (12): 832-838, 2021.
Article in Chinese | WPRIM | ID: wpr-875816

ABSTRACT

OBJECTIVE:To optimize the extraction technology of Zhideke granules. ME THODS:The extraction technology (water extraction ,alcohol extraction ,water extraction and ethanol precipitation )of Zhideke granules was initially screened by ammonia-induced cough experiment and xylene-induced ear swelling experiment in mice. Based on its preparation route ,the immersion time of medicinal materials containing volatile oil was investigated with water absorption as index firstly. The single factor test was adopted to investigate the amount of water added and the extraction time taking the volatile oil yield as index to optimize the extraction technology of medicinal materials containing volatile oil. Taking the contents of irisflorentin and total flavonoids as indicators ,on the basis of single factor investigation ,orthogonal test was adopted to examine the influence of three factors including the amount of water added ,extraction time and extraction frequency ,so as to optimize the water extraction technology of Zhideke granules and the validation tests were conducted. RESULTS :The results of pharmacodynamics experiment showed that the cough latency of mice in water extract low-dose and high-dose groups (6.34,12.68 g/kg,by crude drug )and water-extraction alcohol-precipitation extract high-dose group (12.68 g/kg,by crude drug )were significantly longer than those inmodel group ,and the number of cough within 2 minutes was significantly reduced (P<0.05 or P<0.01). Compared with model group , the ear swelling of mice in water extract low-dose and high-dose groups (6.34,12.68 g/kg,by crude drug),ethanol extract high-dose group (12.68 g/kg,by crude drug) and water-extraction alcohol-precipitation extract hig dose group (12.68 g/kg,by crude drug ) were decreased significantly (P<0.05 or P<0.01). The swelling inhibition rates were 42.26%,55.08%,33.49%,51.56%,39.57% and 44.36% in low-dose and high-dose groups of water extract ,alcohol extract , water-extraction and alcohol-precipitation extract respectively ,indicating that the water extract had better antitussive and anti-inflammatory effects. The optimal extraction technology of volatile oil was adding 5-fold water ,soaking for 30 minutes,and extracting for 3 hours. The optimal water extraction technology was adding 12-fold water ,extracting for 3 times after soaked for 50 min,lasting for 1 h each time. Results of 3 times of validation tests showed that average content of irisflorentin in the extract obtained by optimal technology was 76.47 μg/g(RSD= 2.15%,n=3)and the average content of total flavonoids was 92.45 mg/g(RSD=0.48%,n=3). CONCLUSIONS :The optimal extraction technology of Zhideke granules is stable and feasible.

10.
Acta Pharmaceutica Sinica ; (12): 949-965, 2021.
Article in Chinese | WPRIM | ID: wpr-886976

ABSTRACT

Anxiety disorders are one of the most common mental disorders in adults, the cause of which derives from a combination of genetics and environmental factors. A series of animal models have been established according to their pathogenesis to measure the level of anxiety or induce anxiety only, and these models have been widely applied in the non-clinical evaluation of anxiolytics. In this review, we present the current trends in the study of anxiety disorders and summarize typical non-clinical anxiety animal models, including models that both measure anxiety levels and induce anxiety, and models that induce anxiety only. This review summarizes the important issues in standardized non-clinical research of anxiety disorders and proposes criteria for the selection of an appropriate R&D model.

11.
Organ Transplantation ; (6): 489-2021.
Article in Chinese | WPRIM | ID: wpr-881536

ABSTRACT

Currently, extracellular concentration measurement is the major approach of therapeutic drug monitoring (TDM) of clinical immunosuppressant in organ transplantation. Its correlation with the efficacy of immunosuppressant remains elusive. With widespread application of liquid chromatography, the detection technology of intracellular concentration of immunosuppressant is gradually mature. Theoretically, it may more accurately reflect the efficacy of immunosuppressant due to that the level of drug exposure in target cells can be directly measured. In this article, the history and present situation of the determination of intracellular concentration of immunosuppressant were summarized, and the association between the determination methods of intracellular concentration of immunosuppressant and drug efficacy was emphatically analyzed. Detection of intracellular concentration of immunosuppressant possesses better application value in clinical practice, which is worthy of promotion in clinical settings.

12.
Acta Pharmaceutica Sinica B ; (6): 925-940, 2021.
Article in English | WPRIM | ID: wpr-881177

ABSTRACT

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of

13.
Article in Chinese | WPRIM | ID: wpr-888139

ABSTRACT

This study aims to explore the pharmacodynamic differences of Puerariae Lobatae Radix(PLR), Puerariae Thomsonii Radix(PTR) and their different processed products and the influences of these medical materials on the diversity of intestinal flora. The Sennae Folium-induced diarrhea model, streptozotocin(STZ)-induced diabetes model and L-nitro-arginine methyl ester(L-NAME)-induced hypertension model were used to compare the pharmacodynamic differences in anti-diarrhea, blood glucose reduction and blood pressure lowering among raw, roasted and vinegar-processed PLR and PTR. The effects of raw and processed PLR and PTR on intestinal flora diversity of rats were evaluated by 16 S rDNA high-throughput sequencing. The roasted PLR and PTR performed better in anti-diarrhea, especially the former. PLR and its processed products all presented the efficacy of reducing blood glucose, and the vinegar-processed PLR was the most outstanding. The raw PTR was not that effective in reducing blood glucose, whereas its efficacy was improved after roasting and vinegar processing. Both PLR and PTR were capable of lowering blood pressure to a certain extent, and PLR is superior to PTR in this aspect. Further, the vinegar-processed PLR showed the best effect. The diversity of intestinal flora was different among rats to which different products of PLR and PTR were administered. The roasted PLR led to the highest abundance of Lactobacillus, which was closely related to its best antidiarrheal effect. The highest abilities of vinegar-processed PLR to lower blood glucose and blood pressure were associated with the high abundance of Blautia and Prevotella_9. This study lays a foundation for elucidating the processing mechanisms of PLR and PTR and provides a basis for their further development and application.


Subject(s)
Animals , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Plant Roots , Pueraria , Rats
14.
Rev. invest. clín ; 72(5): 271-279, Sep.-Oct. 2020. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1289717

ABSTRACT

Pharmacogenomics (PGx), one of the several tools of precision medicine, has been slowly implemented in the clinic during the past decades. This process generally starts with direct and indirect genotype-phenotype associations of gene variants and drug efficacy, or adverse drug reactions, followed by replication and validation studies. Institutional efforts led by the PGx Research Network, The PGx Knowledge Base, and The Clinical Pharmacogenetics Implementation Consortium, mine all available data for further validation or research in additional populations. This data mining gives rise to a detailed classification of over 200 drug-gene pairs which, with enough documentation, may become part of a publishable guideline to aid clinicians in drug selection and dosing using genetics. The US Food and Drug Administration utilizes these guidelines to issue warnings and recommendations for specific drugs and their cautioning serves clinicians and pharmacists worldwide. Here, we aim to discuss the steps of this process and list existing actionable drug-gene pairs. Moreover, we describe the current status of PGx knowledge in populations from Mexico for actionable variants on the 19 genes listed by present PGx guidelines affecting 47 drugs. Our review collects current allele frequency information for these actionable variants, lists gaps of PGx information for relevant markers, and highlights the importance of continuing PGx research in Native and Mestizo populations. (REV INVEST CLIN. 2020;72(5):271-9)

15.
Acta Pharmaceutica Sinica ; (12): 91-95, 2020.
Article in Chinese | WPRIM | ID: wpr-780567

ABSTRACT

We compared the pharmacokinetic and pharmacodynamic profiles of desmopressin acetate after intraocular, intravenous and intragastric administration in rabbits to better understand the systemic delivery of peptide drugs through intraocular administration. Fifteen rabbits were randomly divided into three groups (intraocular administration, 7 μg·kg-1; intravenous administration, 0.7 μg·kg-1; and intragastric administration, 7 μg·kg-1). Blood samples were taken from the heart at predetermined time points after dosing and the plasma desmopressin concentration was analyzed by enzyme-linked immunosorbent assay (ELISA). Another 21 rabbits were randomly divided into three groups (intraocular administration, 7 μg·kg-1; intravenous administration, 0.7 μg·kg-1; intragastric administration, 7 μg·kg-1) for a pharmacodynamics study. Urine was collected at predetermined intervals after dosing. The pharmacokinetic parameters after intravenous administration were as follows: Cmax was 143.0 pg·mL-1; the area under the plasma concentration–time curve for desmopressin (AUC0-t) was 999.9 pg·h·mL-1. The pharmacokinetic parameters after intraocular administration were as follows: tmax was 5 min, Cmax was 125.6 pg·mL-1, AUC0-t was 873.1 pg·h·mL-1, and absolute bioavailability (F) was 8.7%. The pharmacokinetic parameters after intragastric administration were as follows: tmax was 10 min, Cmax was 104.1 pg·mL-1, AUC0-t was 451.8 pg·h·mL-1, and absolute bioavailability was 4.5%. Intraocular administration and intravenous administration of one tenth of the dosage showed a similar effect, and the urine volume remained decreased for 12 h, but urine volume increased significantly in the second collection period after intragastric administration, and there was no decrease in volume 12 h after dosing. This study demonstrates that peptide drugs such as desmopressin can be absorbed more rapidly after intraocular administration than after intragastric administration and can exert systemic therapeutic effects. In this study, the program of animal testing had been approved by the Laboratory Animal Care and Use Committee at Anhui University of Chinese Medicine.

16.
Acta Pharmaceutica Sinica B ; (6): 557-568, 2020.
Article in English | WPRIM | ID: wpr-792989

ABSTRACT

, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.

17.
Article in Chinese | WPRIM | ID: wpr-846357

ABSTRACT

Objective: To optimize the prescription and preparation process of "Hugan I" Orally Disintegrating Tablets, and investigate its efficacy against acute liver injury in mice. Methods: Single factor method was used for disintegrants, lubricants, and fillers screening. Taking the appearance, hardness, friability and disintegration time of the tablets as the comprehensive evaluation index, the dosage of disintegrant, micro-silica gel and magnesium stearate was selected as the investigation factor. The Box-Behnken response surface method was used to optimize the orally disintegrating tablets. Acetaminophen (APAP, 500 mg/kg) was used to replicate acute liver injury model by one-time high-dose intragastric administration to investigate the effects of orally disintegrating tablets on the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the content of glutathione (GSH) and malondialdehyde (MDA) and morphological changes in liver tissue. Results: The optimal prescription was as following: dry paste powder 22.00%, microcrystalline cellulose 18.00%, sorbitol 20.00%, mannitol 16.00%, Aspartame 0.50%, citric acid 0.50%, disintegration agent L-HPC 20.00%, micro-powder silica gel 2.50% and magnesium stearate 0.50%. The hardness of the orally disintegrating tablets was 4-7 kg, the mean disintegration time was about 50 s, and the mean friability was around 0.85%. Compared with the model group, there were significant differences (P < 0.01) in Biphenyl diester control group, "Hugan I" Decoction group and "Hugan I" Orally Disintegrating Tablets group, and the levels of ALT and AST in the serum of the mice were significantly decreased, The content of MDA in the liver tissue was decreased, which improved the damage of APAP to liver tissue. Conclusion: The formulation of the "Hugan I" Orally Disintegrating Tablet is feasible and easy to operate, which achieves the same effect with "Hugan I" Decoction that effectively prevent liver damage caused by acetaminophen with no significant differences.

18.
Article in Chinese | WPRIM | ID: wpr-846186

ABSTRACT

Kai-Xin-San (KXS) is a well-known formula that was first recorded in an ancient Chinese book "Important Prescriptions Worth a Thousand Gold for Emergency" by Si-miao Sun from the Tang Dynasty. KXS is composed of Panax ginseng, Poria cocos, Polygala tenuifolia, and Acorus tatarinowii at a ratio of 3:3:2:2. The material basis of the pharmacological action of KXS is mainly related to ginsenosides, polygala saponins, polygala oligosaccharide esters, and polygalactone. However, the active components of P. tenuifolia and A. tatarinowii are less studied, and the research scope is limited. The pharmacological researches of KXS are mainly focused on antidepressant effect, antisenile dementia, improving learning and memory ability, antifatigue, and sedation. The mechanisms involved include nervous system, immune system and endocrine system. The material basis, pharmacological effects and known mechanisms of KXS are systematically described in this paper in order to provide some ideas for the clinical application of KXS in the future.

19.
Article in Chinese | WPRIM | ID: wpr-846128

ABSTRACT

Shengmai Injection (SMI), is a traditional Chinese medicine (TCM) formula injection composed of Panax ginseng, Ophiopogon japonicas and Schisandra chinensis, which is widely used in clinic for the treatment of cardiovascular diseases as well as protecting against pulmonary disease and add-on therapy to cancer chemotherapy. In recent years, the pre-clinical basic research of SMI was widely performed. The studies, including chemical composition, in vivo process, and action mechanism and so on of SMI, helped to provide scientific foundation for revealing the material basis of formula. In this paper, the studies on material composition, pre-clinical pharmacokinetics and pharmacodynamics of this formula were summarized, so as to provide reference for the quality control, second development and rational clinical application of SMI.

20.
Article in Chinese | WPRIM | ID: wpr-845182

ABSTRACT

Objective: To prepare ezetimibe tablets by direct compression technology. Methods: By comparison with the reference standard, the formulation of self-made ezetimibe tablets was optimized using the disintegration time and the release profile similarity factor f2 as the main indexes by the single factor experiments. The pharmacokinetic parameters of ezetimibe tablets in Beagle dog were determined by LC-MS/MS. The pharmacodynamic effects of ezetimibe tablets were evaluated by measuring serum total cholesterol (TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels. Results: Three batches of self-made ezetimibe tablets with the optimal formulation had similar in vitro dissolution behaviors as the reference preparations(f2>70). There was no significant difference in pharmacokinetic parameters in Beagle between the self-made ezetimibe tablets and the reference standard tablets, and the effect on the high serum cholesterol level was similar. Conclusion: The preparation process of the ezetimibe tablet developed in this study is simple, and the self-made tablet has bioequivalence with the reference standard, which provides a reference for the development of the ezetimibe generic drug.

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