A Drug-Drug Multicomponent Crystal of Metformin and Dobesilate: Crystal Structure Analysis and Hygroscopicity Property.

A drug-drug multicomponent crystal consisting of metformin (MET) and dobesilate (DBS) was prospectively connected by solvent cooling and evaporating co-crystallization using the multicomponent crystal strategy, not only to optimize the physicochemical properties of single drugs, but also to play a role in the cooperative effect of DBS with the potential vascular protective effects of MET against diabetic retinopathy (DR). The crystal structure analysis demonstrated that MET and DBS were coupled in a 3D supramolecular structure connected by hydrogen-bonding interactions with a molar ratio of 1:1. Almost all hydrogen bond donors and receptors of MET and DBS participated in the bonding, which hindered the combination of remaining potential hydrogen bond sites and water molecules, resulting in a lower hygroscopicity property than MET alone.

Multicomponent Crystal of Metformin and Barbital: Design, Crystal Structure Analysis and Characterization.

The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures.

A New Co-Crystal of Synthetic Drug Rosiglitazone with Natural Medicine Berberine: Preparation, Crystal Structures, and Dissolution.

A co-crystal of rosiglitazone (Rsg) with berberine (Bbr), Rsg-Bbr, was prepared by the solvent evaporation method and characterized. The results showed that the electrostatic attraction existed between the nitrogen anion of rosiglitazone and the quaternary ammonium cation of berberine, and C-H···O hydrogen bonds were formed between Rsg and Bbr. In the crystal structure, rosiglitazone molecules stack into a supramolecular layer through π-π interactions while π-π interactions between berberine cations also result in a similar layer. The co-crystal presented a low moisture adsorption curve in the range of 0-95% relative humidity values at 25 °C. The improved dissolution rate of rosiglitazone in pH = 6.8 buffer solution could be achieved after forming co-crystal.

A low cost of phosphate-based binder for Mn2+ and NH4+-N simultaneous stabilization in electrolytic manganese residue.

Electrolytic manganese residue (EMR) is a solid waste remained in filters after using sulfuric acid to leaching manganese carbonate ore. EMR contains high concentration of soluble manganese (Mn2+) and ammonia nitrogen (NH4+-N), which seriously pollutes the environment. In this study, a low cost of phosphate based binder for Mn2+ and NH4+-N stabilization in EMR by low grade-MgO (LG-MgO) and superphosphate was studied. The effects of different types of stabilizing agent on the concentrations of NH4+-N and Mn2+, the pH of the EMR leaching solution, stabilizing mechanisms of NH4+-N and Mn2+, leaching test and economic analysis were investigated. The results shown that the pH of the EMR leaching solution was 8.07, and the concentration of Mn2+ was 1.58 mg/L, both of which met the integrated wastewater discharge standard (GB8978-1996), as well as the concentration of NH4+-N decreased from 523.46 mg/L to 32 mg/L, when 4.5 wt.% LG-MgO and 8 wt.% superphosphate dosage were simultaneously used for the stabilization of EMR for 50 d Mn2+ and NH4+-N were mainly stabilized by Mn3(PO4)2·2H2O, MnOOH, Mn3O4, Mn(H2PO4)2·2H2O and NH4MgPO4·6H2O. Economic evaluation revealed that the treatment cost of EMR was $ 11.89/t. This study provides a low-cost materials for NH4+-N and Mn2+ stabilization in EMR.

A Glimepiride-Metformin Multidrug Crystal: Synthesis, Crystal Structure Analysis, and Physicochemical Properties.

A multidrug crystal based on drug combinations was synthesized by the solvent evaporation method. This multicomponent crystal consisted of antidiabetic drugs Glimepiride (Gli) and Metformin (Met), which was performed by single crystal X-ray structure analysis. The results showed an enhancement of the pharmaceutical properties such as lower hygroscopicity and greater accelerated stability than the parent drug Met, and a higher solubility and dissolution rate than Gli.

Microsomal prostaglandin E synthase-1 deficiency exacerbates pulmonary fibrosis induced by bleomycin in mice.

Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1-/-) mice exhibited more severe fibrotic lesions with a decrease in PGE2 content in lungs after bleomycin treatment when compared with wild type (mPGES-1+/+) mice. The mPGES-1 expression levels and PGE2 content were also decreased in bleomycin-treated mPGES-1+/+ mice compared to saline-treated mPGES-1+/+ mice. Moreover, in both mPGES-1-/- and mPGES-1+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2) and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5), siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-ß1 (TGF-ß1)-induced α-smooth muscle actin (α-SMA) protein expression, and the increase was reversed by treatment of PGE2, selective EP2 agonist and focal adhesion kinase (FAK) inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE2-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients.