Randomly Methylated -Cyclodextrin Inclusion Complex with Ketoconazole: Preparation, Characterization, and Improvement of Pharmacological Profiles.

As a powerful imidazole antifungal drug, ketoconazole's low solubility (0.017 mg/mL), together with its odor and irritation, limited its clinical applications. The inclusion complex of ketoconazole with randomly methylated -cyclodextrin was prepared by using an aqueous solution method after cyclodextrin selection through phase solubility studies, complexation methods, and condition selection through single factor and orthogonal strategies.

A Comparative Study of Hearing Handicap Inventory and Pure-Tone Audiometry Scores in Unilateral Hearing Impaired Patients.

To investigate the consistency between the hearing handicap inventory (HHI) and pure-tone audiometry (PTA) scores in assessing hearing status to provide valuable insights for clinical application. Retrospective analysis of clinical data and the HHI reporting status of 6540 patients admitted between April 2020 and July 2022 for self-reported unilateral hearing loss who met the study inclusion and exclusion criteria. The kappa coefficient was used to evaluate the consistency of HHI and PTA in assessing the hearing status of the participants.

Solubility and Pharmacokinetic Profile Improvement of Griseofulvin through Supercritical Carbon Dioxide-Assisted Complexation with HP--Cyclodextrin.

Since griseofulvin was marketed as a non-polyene antifungal antibiotic drug in 1958, its poor water solubility has been an issue for its wide applications, and over the last sixty years, many attempts have been made to increase its water solubility; however, a significant result has yet to be achieved. Through supercritical carbon dioxide-assisted cyclodextrin complexation with the addition of a trace amount of water-soluble polymer surfactant, the griseofulvin inclusion complex with HP--cyclodextrin was prepared and confirmed. The 1:2 ratio of griseofulvin and HP--cyclodextrin in the complex was determined based on its NMR study.

The Use of Cyclodextrin Inclusion Complexes to Increase the Solubility and Pharmacokinetic Profile of Albendazole.

Albendazole is the preferred deworming drug and has strong insecticidal effects on human and animal helminth parasites, showing remarkable activity against hepatocellular carcinoma and colorectal cancer cells. However, it is classified as being in class II in the Biopharmaceutics Classification System due to its poor water solubility (0.2 mg/L) and high permeability, which make the clinical application of albendazole impractical.

F18:A-:B1 Plasmids Carrying Are Prevalent among Isolated from Duck-Fish Polyculture Farms.

We determined the prevalence and molecular characteristics of -positive () isolated from duck-fish polyculture farms in Guangzhou, China. A total of 914 strains were isolated from 2008 duck and environmental samples (water, soil and plants) collected from four duck fish polyculture farms between 2017 and 2019. Among them, 196 strains were CTX-M-1G-positive strains by PCR, and 177 (90%) -producing strains were -positive.

Improvement of solubility and pharmacokinetic profile of hepatoprotector icariin through complexation with HP--cyclodextrin.

Icariin as a hepatoprotector from can expand the cardiovascular and cerebral blood vessels, promote hematopoietic functions, enhance the immune system and show anti-liver tumor activities. However, its low solubility (0.02 mg/mL) limits its clinical applications as food and medical supplements.

Tilmicosin/γ-Cyclodextrin complexation through supercritical carbon dioxide assistance and its pharmacokinetic and antibacterial study.

Tilmicosin, as an effective broad-spectrum antibacterial drug, has incomplete absorption and low bioavailability due to its low water solubility, which limits its veterinary clinical applications. As a non-polymeric drug carrier, γ-cyclodextrin was complexed with tilmicosin through supercritical carbon dioxide assistance for the first time, and confirmed by FTIR, X-ray diffraction, proton NMR and scanning electron microscopy. The water solubility of tilmicosin was increased 57-fold through complexation with γ-cyclodextrin, and the release and bioavailability of tilmicosin in the complex were significantly improved.

Design and Synthesis of Lactose, Galactose and Cholic Acid Related Dual Conjugated Chitosan Derivatives as Potential Anti Liver Cancer Drug Carriers.

Cholic acid and galactose or lactose dual conjugated chitosan derivatives were designed and synthesized as potential anti liver cancer drug carriers, their structures were characterized through proton NMR spectra, elemental analysis, size distribution, zeta potential, and scanning electron microscope image studies. The ability of the dual conjugates to enhance the aqueous solubility of the cancer drug sorafenib was evaluated. The entrapment efficiency (EE%) and drug content (DC%) of sorafenib in the inclusion complexes were measured.

Li Maneuver for geotropic horizontal canal benign paroxysmal positional vertigo (HC-BPPV) -A better choice.

Purpose: This study aimed to retrospectively evaluate the efficacy of Li Maneuver as a repositioning maneuver for geotropic HC-BPPV, compared with Gufon Maneuver.

Methods: Data of geotropic HC-BPPV patients treated at our department between January 2009 and January 2020 was retrospectively collected and analyzed. Enrolled cases were divided into Gufoni Group and Li Group.

Formation of inclusion complex of enrofloxacin with 2-hydroxypropyl--cyclodextrin.

Enrofloxacin, a third-generation fluoroquinolone, is a broad-spectrum antimicrobial drug against a lot of veterinary bacterial diseases. However, bactericidal activity of enrofloxacin is concentration-dependent and its poor aqueous solubility and bitter taste limit its development and application. Meanwhile, 2-hydroxypropyl--cyclodextrin (HP-β-CD), a widely used cyclodextrin analog, is a safe and an effective drug carrier.

An ex vivo abomasal ovine model to study the immediate immune response in the context of Haemonchus contortus larval-stage.

We have set up an ex vivo ovine abomasal model, which can mimic the multicellular process to explore the early steps in haemonchine nematode infection using RNA-seq technology. Ovine abomasal explants were collected for histological and transcriptional analysis and supernatants collected to quantitate lactate dehydrogenase (LDH) enzymes. Atotal of 233 were substantially induced genes between L-inoculated and uninoculated-control tissues, respectively.

Synthesis of carbohydrate conjugated 6A,6D-bifunctionalized β cyclodextrin derivatives as potential liver cancer drug carriers.

Galactosyl and lactosyl conjugated 6A,6D-bifunctionlized β cyclodextrin derivatives were designed and synthesized as the potential liver cancer drug carriers through SN2 replacement and click reactions in order to increase liver cancer drug's targeting ability, solubility and stability. The synthetic methods and strategies to obtain the designed compounds were discussed.

Efficient and practical synthesis of Fondaparinux.

Combining advantageous sequences of Alchemia and Sanofi methods of synthesis of Fondaparinux, a more efficient and practical synthetic strategy for the synthesis of corresponding protected pentasaccharide was developed. The protected pentasaccharide was smoothly converted into Fondaparinux in overall high yield (1%).

Design, synthesis, and evaluation of novel 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective CXCR2 chemokine receptor antagonists.

We describe herein a novel series of 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective inhibitors against the CXCR2 chemokine receptor and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Furthermore, these alkyl-hydrazine series inhibitors such as 5b demonstrated acceptable metabolic stability when incubated in human and rat microsomes.

Novel thiazolones as HCV NS5B polymerase allosteric inhibitors: Further designs, SAR, and X-ray complex structure.

Structure-activity relationships (SAR) of 1 against HCV NS5B polymerase were described. SAR explorations and further structure-based design led to the identifications of 2 and 3 as novel HCV NS5B inhibitors. X-ray structure of 3 in complex with NS5B polymerase was obtained at a resolution of 2.

Synthesis of thiazolone-based sulfonamides as inhibitors of HCV NS5B polymerase.

Several thiazolone-based sulfonamides were prepared, utilizing various hetero-aryl sulfonyl chlorides and different aldehydes, as inhibitors of NS5B polymerase, to target HCV. The best compound showed 0.6 microM [corrected] of IC50 inhibitory activity.

Parallel synthesis of 5-cyano-6-aryl-2-thiouracil derivatives as inhibitors for hepatitis C viral NS5B RNA-dependent RNA polymerase.

From random screening of our compound libraries, we identified a hit compound with an IC50 of 27 microM against hepatitis C viral NS5B RNA-dependent RNA polymerase. By using a parallel synthetic strategy, a series of its derivatives were synthesized. From their anti-HCV activity screening, compounds with single digital 3.

Synthesis of 2'-beta-C-methyl toyocamycin and sangivamycin analogues as potential HCV inhibitors.

Coupling reaction of 2-beta-C-methyl-1,2,3,4-tetra-O-benzoyl-d-ribofuranose with 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine, followed by debromination and debenzoylation, gave the 2'-beta-C-methyl toyocamycin in high yield. Based on this result, a series of 2'-beta-C-methyl-4-substituted toyocamycin and sangivamycin analogues were synthesized for biological screening as potential inhibitors of HCV RNA replication.

Synthesis of 9-(2-beta-C-methyl-beta-d-ribofuranosyl)-6-substituted purine derivatives as inhibitors of HCV RNA replication.

A series of 9-(2'-beta-C-methyl-beta-d-ribofuranosyl)-6-substituted purine derivatives were synthesized as potential inhibitors of HCV RNA replication. Their inhibitory activities in a cell based HCV replicon assay were reported. A prodrug approach was used to further improve the potency of these compounds by increasing the intracellular levels of 5'-monophosphate metabolites.

Parallel synthesis of pteridine derivatives as potent inhibitors for hepatitis C virus NS5B RNA-dependent RNA polymerase.

From compound library screening using an HCV NS5B RNA-dependent RNA polymerase enzymatic assay, we identified a pteridine hit compound with an IC(50) of 15 microM. Our SAR studies were focused on the different groups at the 6- and 7-positions, substitutions at the 4-position, and replacement of N(1) or N(3) with carbon in the pteridine ring. We found that NH or OH at 4-position is critical for the inhibitory activity.

Synthesis of new 2'-beta-C-methyl related triciribine analogues as anti-HCV agents.

Ten new beta-D-ribofuranosyl and 2'-beta-C-methyl-beta-D-ribofuranosyl triciribine derivatives 4-13 with various N4 and 6-N substituents on the tricyclic ring were synthesized from the corresponding toyocamycin and new 2'-beta-C-methyl toyocamycin derivatives. The inhibitory studies of these compounds in the HCV replicon assay reveal that some of them possess interesting anti-HCV properties with low cytotoxicity.

Synthesis of new 3'-, 5-, and N(4)-modified 2'-O-methylcytidine libraries on solid support.

A versatile solid phase combinatorial approach was developed and utilized for the rapid synthesis of new 2'-O-methylcytidine nucleoside libraries 1-7 containing 672 compounds with 3'-deoxy-3'-C-methyl, 3'-deoxy-3'-C-hydroxymethyl, and 5-alkyl/alkynyl modifications. The modified uridine scaffolds 8-10, 23-25, and 31 were loaded onto the 4-methoxytrityl chloride (MMT-Cl) polystyrene resin through the hydroxyl groups at the 5'-position as well as on the substituents at the 3'- and 5-positions. The scaffolds loaded on the resin were orthogonally protected by MMT group on the resin itself and TBDMS or acetyl protecting groups.