OBJECTIVES: The aims of this study were to investigate the feasibility of isosorbide delivery into perilymph through the round window membrane (RWM), and to compare the intracochlear isosorbide concentration in perilymph after oral administration (PO) versus that after round window perfusion (RWP). METHODS: Sixteen male guinea pigs (32 ears) were used. Isosorbide, an osmotic diuretic, was administered via RWP or PO. First, to investigate the optimal perfusion time, perilymph sampling of scala tympani from the RWM was performed after RWP for 15, 30, or 60 minutes. Second, to compare the drug concentration after RWP versus that after PO, perilymph was aspirated at 3 and 6 hours after administration. Intracochlear concentration of isosorbide was analyzed by high-performance liquid chromatography coupled to refractive index detection. RESULTS: Isosorbide passed through the RWM into perilymph after RWP. After RWP for 15, 30, and 60 minutes, mean isosorbide concentrations in perilymph were 116.27+/-44.65, 245.48+/-112.84, and 279.78+/-186.32 mM, respectively. The intracochlear concentration after RWP for 30 minutes was higher than that after RWP for 15 minutes (P=0.043). At 3 and 6 hours after PO, isosorbide concentrations in perilymph were 28.88+/-4.69 and 12.67+/-2.28 mM, respectively. In contrast, the corresponding concentrations after RWP were 117.91+/-17.70 and 75.03+/-14.82 mM at 3 and 6 hours, respectively. Isosorbide concentrations in perilymph following RWP were significantly higher than those following PO at both 3 and 6 hours (P=0.025 and P=0.034, respectively). CONCLUSION: Isosorbide can rapidly pass through the RWM after RWP in guinea pigs, and 30 minutes of perfusion is considered to be appropriate. In addition, over a 6-hour period, RWP can deliver higher concentrations of isosorbide into perilymph than those achieved with PO.
Administration, Oral* ; Animals ; Chromatography, Liquid ; Diuretics, Osmotic ; Guinea Pigs* ; Humans ; Isosorbide* ; Male ; Membranes ; Meniere Disease ; Perfusion* ; Perilymph* ; Refractometry ; Scala Tympani

We prepared the isosorbide-5-mononitrate pulsatile controlled-release pellets (PCRP) and studied the influencing factors in vitro. The isosorbide-5-mononitrate (5-ISMN) pellets prepared by extrusion-spheronization technology were coated with swelling material as the inner coating swelling layer, and with ethylcellulose aqueous dispersion as the outer coating controlled layer. The influences of the coating materials of the swelling layer, the coating levels of the swelling layer and controlled layer,and the pH values of the media on the release of 5-ISMN from PCRP were investigated. The drug release from the pellets was pulsatile. The ISMN-5-PCRP, with a lag time of 5 h and more than 80% released within the following 1.5 h,were prepared by using the low-substituted hydroxypropyl cellulose as the inner swelling layer with 15% (weight) in coating thickness, and the ethylcellulose aqueous dispersion as the outer controlling layer with 13% (weight) in coating thickness.
Capsules ; Cellulose ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; chemistry ; Hypromellose Derivatives ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry

Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; therapeutic use ; Cephalosporins ; administration & dosage ; Enterobacter cloacae ; Enterobacteriaceae Infections ; drug therapy ; Female ; Gentamicins ; adverse effects ; Humans ; Imipenem ; adverse effects ; Isosorbide Dinitrate ; adverse effects ; analogs & derivatives ; Male ; Ofloxacin ; adverse effects ; Software

The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.
Administration, Cutaneous ; Animals ; Arginine ; chemical synthesis ; chemistry ; pharmacology ; Aspirin ; administration & dosage ; pharmacokinetics ; Cell Line ; Cell Survival ; drug effects ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; pharmacology ; Chitosan ; chemical synthesis ; chemistry ; pharmacology ; Drug Carriers ; Humans ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Keratinocytes ; cytology ; Male ; Mice ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Skin Absorption ; drug effects

No abstract available.
Adrenergic beta-Antagonists/administration & dosage/*therapeutic use ; Drug Therapy, Combination ; Esophageal and Gastric Varices/complications/*drug therapy ; Gastrointestinal Hemorrhage/complications/physiopathology/*prevention & control ; Hepatic Veins/*physiopathology ; Humans ; Isosorbide/administration & dosage/therapeutic use ; Liver Cirrhosis/*complications ; Peritonitis/complications ; Propranolol/administration & dosage/therapeutic use ; Venous Pressure

OBJECTIVEBased on real world research the circumstances of the clinical use of usual drugs combined with salvianolate injection are surveyed.

METHODDescriptive statistics on the use of salvianolate injection in 18 general hospitals in China.

RESULTIn 1 605 patients with coronary heart disease (CHD), salvianolate injection was most frequently (51%) combined with clopidogrel and isosorbide dinitrate. In addition this combination showed a higher clinical effectiveness as compared with other drug combinations.

CONCLUSIONIn the real world, salvianolate injection combined with usual treatment was found to be more effective than other treatment combinations. In addition practice conformed to the clinical treatment of coronary heart disease (CHD) guidelines for drug use. However, liver and kidney function, routine blood tests and the blood's coagulation function require ongoing monitoring.

Aged ; Aged, 80 and over ; Coronary Disease ; drug therapy ; mortality ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hospital Information Systems ; statistics & numerical data ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Male ; Middle Aged ; Plant Extracts ; administration & dosage ; Pragmatic Clinical Trials as Topic ; Propensity Score ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome

OBJECTIVETo understand the clinical circumstances for the use of parenterally administered Shenfu in the treatment of coronary heart disease, in order to provide a reference guide for its clinical use.

METHODInformation was extracted and summarized on the treatment of coronary heart disease patients, who received parenterally administered Shenfu, from 20 nationwide general hospitals HIS data. Descriptive statistical methods were used to analyze the usage and dosage. Correlation analysis was adopted to analyze information including drug combinations, and outcomes were compared with other combinations.

RESULTReal world HIS data showed that the drug delivery method for parenterally administered Shenfu was intravenous infusion. Treatment courses were from 3 to7 days, at a dosage of 60 mL. The drug combination was mostly with chemical drugs. The most common combinations were Shenfu plus clopidogrel, aspirin and isosorbide dinitrate.

CONCLUSIONParenterally administered Shenfu is a common drug used in the treatment of coronary heart disease. Most of the usage was in accordance with instructions. The chemical combination drugs were mainly clopidogrel, aspirin and isosorbide dinitrate.

Adult ; Aged ; Aged, 80 and over ; Aspirin ; therapeutic use ; Coronary Disease ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Hospital Information Systems ; statistics & numerical data ; Humans ; Infusions, Parenteral ; Isosorbide Dinitrate ; therapeutic use ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Pragmatic Clinical Trials as Topic

The aim of this study is to investigate the effect of isosorbide-5-mononitrate (ISMN) on the electric field stimulation induced sympathetic purinergic vasoconstriction of the rabbit saphenous arterial rings. Isometric vasoconstrictive responses to electric field stimulation and to exogenous noradrenaline and adenosine triphosphate were recorded. We found that the vasoconstrictive responses to electric field stimulation (15 V, 1 ms pulse duration, 2 - 16 Hz) were frequency-dependant in the rabbit saphenous arterial rings, and abolished by tetrodotoxin (0.1 micromol x L(-1)). The alpha1-adrenoceptor antagonist prazosin (1 micromol x L(-1)) did not affect the vascular responses to the electric field stimulation (2 -8 Hz). After a combination treatment with both alpha,beta-meATP (3 micromol x L(-1), desensitizing P2X1 receptors) and prazosin (1 micromol x L(-1)), the vasoconstrictive responses to electric field stimulation were abolished. When the arterial preparation was treated with ISMN (one preparation was exposed to only one concentration of ISMN), ISMN at 0.1 mmol x L(-1) significantly inhibited the vasoconstriction induced by electric stimulation at 8 Hz, 0.3 and 1.0 mmol x L(-1) significantly inhibited the vasoconstrictive responses to electric stimulation at 2 - 16 Hz. The highest concentration of ISMN (1.0 mmol x L(-1)) reduced the vasoconstrictive responses by 46% (2 Hz), 47% (4 Hz), 34% (8 Hz) and 22% (16 Hz), separately. ISMN (0.3 and 1.0 mmol x L(-1)) did not affect the vascular responses to exogenous noradrenaline (0.01-100 micromol x L(-1)) and adenosine triphosphate (1 mmol x L(-1)). It is reasonable to suggest that ISMN inhibits the purinergic vasoconstriction induced by sympathetic nerve stimulation via a prejunctional mechanism.
Adenosine Triphosphate ; analogs & derivatives ; pharmacology ; Adrenergic alpha-Antagonists ; pharmacology ; Animals ; Arteries ; drug effects ; Delayed-Action Preparations ; Electric Stimulation ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacology ; Male ; Norepinephrine ; pharmacology ; Prazosin ; pharmacology ; Purinergic P2 Receptor Agonists ; Rabbits ; Receptors, Purinergic P2X ; Vasoconstriction ; drug effects

OBJECTIVETo investigate the effect and mechanism of Compound Salvia injection (CSI) on nitrate ester tolerance.

METHODSEighty-four patients with coronary heart disease (CHD) were randomly divided into three groups, Group A treated with isosorbide dinitrate (ISD, 15 mg, 4 times per day) alone, Group B with ISD plus CSI and Group C with ISD plus vitamin C. The therapeutic course for all groups was 10 days. The tolerance to nitrate ester and blood pressure were monitored. Before and after treatment, the color Doppler ultrasonic apparatus was used to detect the baseline value of humeral arterial internal diameters (D0), the humeral arterial dilatory response under compression [D1, that is, the flow-mediated vasodilation (FMD)] and the vasodilatory response after sucking of nitroglycerin (D2). And the blood levels of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) mRNA expression were determined. The endothelial-dependent vasodilation (EDD) was expressed by (D1 - D0)/D0 x 100%, and the endothelial-independent vasodilation (EID) was expressed by (D2 - D0)/D0 x 100%.

RESULTS(1) The occurrence rate of nitrate tolerance in Group B and C (28.57% and 35.7%) was lower than that in Group A (64.29%), but insignificant difference was found between the former two. (2) After treatment, blood pressure increased in Group A to the level of pre-treatment, that in Group C also increased but still lower than that of pre-treatment, while insignificant increase was observed in Group B, comparison between Group B and C showed significant difference (P < 0.05). (3) After treatment, EID lowered in Group A, EDD increased in Group B and C (P < 0.05), EDD and EID in Group B and C were higher than those in Group A (P < 0.05), and EDD was higher in Group B than in Group C (P < 0.05). (4) After treatment, ET-1 mRNA expression lowered in Group B, eNOS mRNA expression increased in Group B and C, with significant difference as compared with those before treatment and those in Group A (P < 0.05), and eNOS mRNA expression in Group C was lower than that in Group B (P < 0.05).

CONCLUSIONCSI could partially prevent the occurrence of tolerance to nitrate ester, with the effect better than vitamin C, the mechanism might be related with its regulation on eNOS, ET-1 mRNA expression and protection on vascular endothelial function.

Adult ; Aged ; Coronary Disease ; drug therapy ; Drug Resistance ; Drugs, Chinese Herbal ; administration & dosage ; Endothelin-1 ; biosynthesis ; genetics ; Female ; Humans ; Injections, Intravenous ; Isosorbide Dinitrate ; therapeutic use ; Male ; Middle Aged ; Nitric Oxide Synthase ; biosynthesis ; genetics ; Nitric Oxide Synthase Type III ; Phytotherapy ; RNA, Messenger ; biosynthesis ; genetics ; Salvia miltiorrhiza ; Vasodilator Agents ; therapeutic use

OBJECTIVETo investigate the clinical effect of manshuailing oral liquid on patients with congestive heart failure of type heart and kidney Yang deficiency.

METHOD90 patients of heart failure were randomly divided into 2 groups. 45 cases in the routine treatment group (RT) received general therapy including diuretics and digitalis, and 45 cases in the Chinese herb medicine group (CH) were treated basically with the above medicine, with additional manshuailing oral liquid. The clinical effect was summarized 6 weeks after treatment.

RESULTTotal effect rate was 82.2% and 62.2% in CH and RTgroup respectively. Compared with pretreatment, heart function including stroke volume (SV), stroke volume index (SVI), cardiac index (CI), shorten rate of left ventricular short axe (deltaD%), distance of inter-ventricular septal to mitral valve (EPSS) were all improved significantly in both groups (P < 0.05 or P < 0.01), and with even better effects in the CH group than the RT group (P < 0.05 or P < 0.01), except the SV.

CONCLUSIONManshuailing oral liquid can alleviate clinical symptom, decreased EPSS, increase deltaD% and improve heart function.

Administration, Oral ; Adult ; Aged ; Cardiotonic Agents ; therapeutic use ; Combined Modality Therapy ; Diagnosis, Differential ; Digoxin ; therapeutic use ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; therapeutic use ; Female ; Heart Failure ; drug therapy ; physiopathology ; Heart Function Tests ; Humans ; Hydrochlorothiazide ; therapeutic use ; Isosorbide Dinitrate ; therapeutic use ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Plants, Medicinal ; chemistry ; Sodium Chloride Symporter Inhibitors ; therapeutic use ; Vasodilator Agents ; therapeutic use ; Yang Deficiency ; drug therapy