salicylates and betadex

The cytoprotective prostaglandin E2 analog nocloprost clathrate (NOCLO) is tested as a prophylactic for gastrointestinal lesions of NSAID. The effects of 400 micrograms NOCLO versus respective placebos with and without equivalent amounts of beta-cyclodextrin on the pharmacokinetic behavior of acetylsalicylic acid (ASA), given 30 min after NOCLO, were studied in two single-blind, parallel-group trials. The trials were performed in 15 male healthy volunteers (age 21-25 years, body weight 62-94 kg, body height 172-187 cm) with known N-acetylation and debrisoquine type hydroxylation phenotype. ASA, salicylic acid (SA), and salicyluric acid (SU) in plasma and SA and SU in urine were measured by HPLC. NOCLO delayed the absorption of ASA (increased tmax, lower Cmax) significantly in comparison with both placebos. AUC and clearance values were not changed by NOCLO premedication. There were neither differences between the two placebo groups nor between the two groups pretreated with NOCLO with regard to any pharmacokinetic parameter. The changes in drug absorption are caused by the sum of those cytoprotective effects of prostaglandin which are also determinants of drug absorption.

Topics: Acetylation; Administration, Oral; Adult; Aspirin; beta-Cyclodextrins; Chromatography, High Pressure Liquid; Cyclodextrins; Drug Interactions; Hippurates; Humans; Intestinal Absorption; Male; Prostaglandins F, Synthetic; Salicylates; Salicylic Acid; Single-Blind Method; Vasodilator Agents

Oxidative stress is the hallmark of several pathologies like arthritis, hypertension and many neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. In this scenario, antioxidant compounds can play a pivotal role in treating these severe pathologies. The synthesis of molecules able to mimic physiologically-relevant proteins is nowadays of particular interest. Several transition metal complexes, especially manganese(III) complexes with porphyrin and salen-type ligands, have been reported to be superoxide scavengers. Here we report the synthesis and spectroscopic characterization of manganese(III) complexes of 5[4-(6-O-β-cyclodextrin)-phenyl],10,15,20-tri(4-hydroxyphenyl)-porphyrin and of 6(A)-deoxy-6(A)[(S-cysteamidobenzoyl(3,4-diamino)-N,N'-bis(salicylidene))]-β-cyclodextrin. The superoxide dismutase activity of the metal complexes was investigated by indirect methods. The catalase and peroxidase activities were tested using ABTS assays.

Topics: Antioxidants; beta-Cyclodextrins; Catalase; Coordination Complexes; Manganese; Peroxidases; Porphyrins; Salicylates; Superoxide Dismutase

The complexation of methyl salicylate (MS) and ethyl salicylate (ES), non-steroidal analgesic, anti-inflammatory and antirrheumatic drugs with beta-cyclodextrin (betaCD) has been studied from thermodynamic and structural points of view. The complexation with betaCD has been investigated using reversed-phase liquid chromatography. Retention behavior has been analyzed on a reverse-phase column Luna 18(2) 5 microm. The mobile-phase was methanol:water in different ratios (55:45 to 70:30) in which betaCD (1-9 mM) was incorporated as a mobile-phase additive. The decrease in retention times with increasing concentrations of betaCD enables the determination of the apparent stability constant of the complexes. Values at 30 degrees C with 55% methanol were K(MS:betaCD): 15.84 M(-1) and K(ES:betaCD): 12.73 M(-1) for MS and ES, respectively. The apparent stability constants decrease as the polarity of the solvent decreases. The low solubility of MS and ES in aqueous solution has been improved by complexation with betaCD (1-9 mM). The stability constants of the complexes obtained from the phase-solubility diagrams using a UV-vis spectrophotometric method were K(MS:betaCD): 229 M(-1) and K(ES:betaCD): 166 M(-1). In addition, semi-empirical quantum mechanics calculations using AM1 and PM3 methods in vacuum were performed. The energetically favorable inclusion structures were identified and the most favorable orientation for the inclusion process was found to be the head-down orientation for both complexes. Enthalpy for encapsulation processes was found to be favorable (DeltaH degrees <0), while entropy (DeltaS degrees <0) and Gibbs free energy were unfavorable (DeltaG degrees >0). By means of HPLC and UV-vis measurements and quantum mechanics calculations, it was found that MS and ES form a 1:1 inclusion complex with betaCD. The theoretical results are in agreement with the experimental parameters associated with the encapsulation process.

Topics: Antirheumatic Agents; beta-Cyclodextrins; Chromatography, High Pressure Liquid; Kinetics; Models, Molecular; Quantum Theory; Salicylates; Solubility; Spectrophotometry, Ultraviolet; Temperature; Thermodynamics

An effective and novel approach to obtaining electrorheological particles with high performance through the formation of host-guest complexes has been achieved. The significant preponderance of the host-guest complex formation is that the host structure can be controlled easily by adding different guests. Based on this point, six supramolecular complexes of beta-cyclodextrin cross-linking polymer with salicylic acid (beta-CDP-1), 5-chlorosalicylic acid (beta-CDP-2), 3,5-dichlorosalicylic acid (beta-CDP-3), 5-nitrosalicylic acid (beta-CDP-4), 3,5-dinitrosalicylic acid (beta-CDP-5), or 3-hydroxy-2-naphthoic acid (beta-CDP-6) particles were synthesized. The electrorheological yield stresses of the suspensions of these particles in silicone oil have been investigated under DC electric fields. It was found that the yield stress of the typical beta-CDP-1 ER fluid was 5.6 kPa in 4 kV/mm, which is much higher than that of pure beta-cyclodextrin polymer (beta-CDP), that of pure salicylic acid as well as that of the mixture of the host with the guest. It is clearly indicated that the formation of supramolecular complexes between beta-CDP and salicylic acid can enhance the ER properties of the host. The similar results for other supramolecular complexes with different guests have also been obtained under the same DC electric fields. The yield stress of supramolecular complexes is strongly affected by the structure of guests. Among the six investigated guests, 3-hydroxy-2-naphthoic acid gave the highest ER property having a yield stress of 9.8 kPa under 4 kV/mm DC while cross-linked with beta-CDP to form beta-CDP-6. The yield stress of beta-CDP-6 was significantly increased by 72% in comparison with that of the pure beta-CDP. However, the yield stress of beta-CDP-1-5 slightly increased by 34-41% as compared with that of the pure beta-CDP. The achieved results indicate that the ER effect of host-guest complexes can be greatly affected by the changes of the tremendous guest structure, whereas the slight guest structural transposition, such as altering different groups of a guest, can only obtain the adjacent electrorheological behavior. The dielectric properties of these host-guest complexes also proved that the ER effect can be affected by the properties of guest.

Topics: beta-Cyclodextrins; Chlorobenzoates; Electrophoresis; Molecular Structure; Naphthols; Particle Size; Polymers; Rheology; Salicylates; Salicylic Acid; Silicone Oils; Static Electricity

Capillary zone electrophoresis (CZE) methods with indirect absorbance detection for analyzing mixtures of alpha-, beta-, and gamma-cyclodextrins (CDs) and their derivatives have been developed. Benzylamine, salicylic, sorbic, or 1-naphthylacetic acid (NAA) was utilized as background electrolyte (BGE) and absorbance provider. Separation of alpha-, beta-, and gamma-CD could be achieved in less than 18 min when the CZE was run in 2 mM NAA or 5 mM sorbate solution (pH 12.2) and detected by indirect absorbance at 222 or 254 nm, respectively. Mixtures of alpha- and beta-CDs, and dimethyl- and trimethyl-derivatives of beta-CD could also be analyzed by CZE, using 50 mM salicylic acid or benzylamine solution (pH 6.0) as BGE with indirect absorbance detection at 230 and 210 nm, respectively. CZE methods for determining the inclusion complex formation constants of various CDs for salicylic acid or benzylamine with either direct or indirect absorbance detection have also been developed. The formation constants of salicylate are in the range from ca. 8 +/- 0.3 mole-1 for the complex with alpha-CD to ca. 99 +/- 2 molarity-1 for the complex with methyl-beta-CD. The detection limits (determined at a signal-to-noise ratio of 3) for the NAA and the salicylate system are ca. 0.1 mM and 1 mM, respectively.

Topics: alpha-Cyclodextrins; Benzylamines; beta-Cyclodextrins; Cyclodextrins; Electrolytes; Electrophoresis, Capillary; gamma-Cyclodextrins; Naphthaleneacetic Acids; Salicylates; Salicylic Acid; Sorbic Acid

After oral administration of 14C-labelled salicylic acid and its beta-cyclodextrin complex to rats, the blood radioactivity-level increases in the first 2 h than decreases. The blood level obtained with the inclusion complex is somewhat but not significantly lower than with free acid. Since the resorption of cyclodextrin is a considerably slower process, it is very likely that the resorption of salicylic acid take place in the form of free acid after dissociation of the complex. The urinary excretion cumulative curves show that the free salicylic acid is completely excreted, while about 10% of the salicylic acid administered in the form of complex is lost. The cyclodextrin complex formation increases the pK value of all hydroxy-benzoic acids. Direct observations reveals that complex formation decreases the stomach-irritating effect of salicylic acid. The ratio of radioactivity was nearly the same in the organs of animals treated by both free salicylic and cyclodextrin complex.

Topics: Animals; beta-Cyclodextrins; Cyclodextrins; Dextrins; Diffusion; Female; Irritants; Male; Powders; Rats; Salicylates; Starch; Stomach; Tissue Distribution; X-Ray Diffraction