betadex and puerarin

To study the interaction of drugs of different properties, namely puerarin, borneol and catalpol in the process of in- clusion, in order to explore the inclusion regularity of multi-component and multi-property traditional Chinese medicine compound in- clusions. With HP-β-CD as the inclusion material, the freeze-drying method was used to prepare the inclusion. The inclusion between puerarin, borneol and catalpol was tested by measuring the inclusion concentration, DSC and X-ray diffraction. According to the find- ings, when insoluble drugs puerarin and borneol were included simultaneously, and puerarin was overdosed, puerarin included was almost equal to puerarin included, and borneol was not included. When puerarin was under-dosed, and HP-β-CD was overdosed, borne- ol was included, and the simultaneous inclusion was lower than the separate inclusion of borneol. When water-soluble drug catalpol was jointly included with puerarin or borneol, the simultaneous inclusion was almost the same with their separate inclusion, without charac- teristic peak of catalpol in DSC and X-ray diffraction patterns. There is a competition in the simultaneous inclusion between water-solu- ble drugs puerarin and borneol and a stronger competition in puerarin. The water-soluble drug catalpol could be included with HP-β-CD with no impact on the inclusion of puerarin or borneol.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Brain Ischemia; Camphanes; Drug Compounding; Freeze Drying; Iridoid Glucosides; Isoflavones; Solubility

It is well known that puerarin attenuates ischemia-reperfusion injury and promotes function recovery of ischemic region. However, due to its reverse physiochemical properties, puerarin does not easily cross the blood-brain barrier. The aim of the present study is to create puerarin nanoparticles which increase and prolong the puerarin concentration in the brain. Using emulsion solvent evaporation techniques, we designed puerarin-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles. Hydroxypropyl beta cyclodextrin (HP-β-CD) was used to increase the solubility of puerarin and gelatin to enhance viscosity of inner water phase, which improved puerarin entrapment. The drug release kinetics and nanoparticle degradation in phosphate buffered saline (PBS) were analyzed by electronic microscopy and high-performance liquid chromatography. Computerized tomography scans were used to detect the infarction volume and electroencephalogram (EEG) was recorded to estimate the recovery of brain function. The results showed that the combined HP-β-CD and gelatin significantly improved the entrapment efficiency. The infarction volume was significantly decreased on days 3 and 7 after the administration of puerarin nanoparticles compared with that of control and pure puerarin. EEG was also significantly improved. Puerarin nanoparticles are potentially applicable for the brain injury induced by ischemic-reperfusion.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Biological Availability; Blood-Brain Barrier; Brain Ischemia; Chromatography, High Pressure Liquid; Drug Carriers; Gelatin; Isoflavones; Lactic Acid; Male; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Wistar; Reperfusion Injury; Solubility; Time Factors; Tissue Distribution; Tomography, X-Ray Computed; Vasodilator Agents; Viscosity

Acetic acid acts as one component of the mobile phase to influence separation of puerarin from daidzin when using β-cyclodextrin-substituted media. In this work considering an explicit acetic acid solution, host-guest complexes of β-cyclodextrin (β-CD) with puerarin and daidzin were investigated by molecular dynamics simulations. Computational results indicate different shuttle motions of puerarin and daidzin inside the cavity of β-CD. A model detailing the shuttle motion was constructed, and the relationships between shuttle depth and guest rotation angles, hydrogen bonds, and host-guest interaction energies were analyzed. The results can be used to explain the chromatographic retention mechanisms of puerarin and daidzin with β-CD, and to explore the complexity of host-guest interactions involving β-CD.

Topics: Acetic Acid; beta-Cyclodextrins; Chromatography; Isoflavones; Models, Molecular; Molecular Dynamics Simulation

In order to differentiate two species of Radix Puerariae (Radix Puerariae lobatae and Radix Puerariae thomsonii) and to determine major isoflavonoids (puerarin, daidzin, daidzein and genistein) in the samples, a simple high performance liquid chromatography (HPLC) method with isocratic elution employing cyclodextrins (CDs) as mobile phase additives was developed. Various factors affecting the retention of isoflavonoids in the C(18) reversed-phase column, such as the nature of CDs, the concentration of hydroxypropyl-β-cyclodextrin (HP-β-CD) and the methanol percentage in the mobile phase, were studied. Experimental results confirmed that HP-β-CD, as a very effective mobile phase additive, could markedly reduce the retention of isoflavonoids, especially daidzein and genistein. The elution of four isoflavonoids could be achieved on a Kromasil(®) C(18) column within 56 min by using the methanol-water contained 5 mM HP-β-CD (25/75, v/v) mixture as the mobile phase. The formation of the inclusion complexes between isoflavonoids and HP-β-CD explained the modification of the retention of analytes. The apparent formation constants determined by HPLC confirmed that the stoichiometry of HP-β-CD-isoflavonoid complexes was 1:1, and the stability of the complexes depended on the size and property of isoflavonoids. The optimized method was successfully applied for the simultaneous determination of major isoflavonoids in P. lobatae and P. thomsonii samples. This work provides a useful method for the analysis of traditional Chinese herbs.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Genistein; Isoflavones; Pueraria

Beta-cyclodextrin (β-CD) is an ideal candidate for a host molecule, and it is used as such in drug delivery and separation technology. The structural behavior of free β-CD and host-guest complexes of β-CD with two isoflavonoid isomers (puerarin and daidzin) in aqueous alcohol solutions, covering methanol, ethanol, 2-propanol, and 1-propanol, was investigated through molecular dynamics (MD) simulations. The MD results highlighted aspects of the structural flexibility and rigidity of β-CD in different alcohol solutions. The alcohol residence time within the β-CD cavity, solvent distribution around β-CD, and guest-induced structural changes were analyzed. Interaction with puerarin endowed β-CD with a more rigid structure than with daidzin and a weaker ternary complex β-CD/puerarin/alcohol was formed with a local participation of water molecules. The retention behavior of puerarin and daidzin on a β-CD-coupled medium was determined via chromatographic experiments and simulation results provided a structural explanation for such interactions.

Topics: Alcohols; beta-Cyclodextrins; Hydrogen Bonding; Isoflavones; Isomerism; Molecular Dynamics Simulation; Solvents

Puerarin is a natural isoflavone, found in the Chinese medicinal plant Ge-gen, with many reported health-promoting properties. However, its low water solubility impedes its application in pharmaceutical and functional food products. This study explores the formation of inclusion complex between puerarin and glucosyl-β-cyclodextrin (G-β-CD) to improve the aqueous solubility of puerarin. The complex was prepared by mixing an equal molar mixture of puerarin and G-β-CD for 24 h, followed by freeze-drying. The obtained complex was analyzed by ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, X-ray diffractometry, and proton nuclear magnetic resonance spectroscopy. Results showed clearly that the process led to the formation of a supramolecular complex in which the guest molecule, puerarin, was entrapped inside the cavity of the host, G-β-CD. The close association between puerarin and G-β-CD resulted in changes in some of the characteristic spectral, phase-transitional, and morphological properties of puerarin.

Topics: beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemical Phenomena; Chemistry, Pharmaceutical; Freeze Drying; Isoflavones; Magnetic Resonance Spectroscopy; Microscopy, Electron, Scanning; Phase Transition; Solubility; Spectroscopy, Fourier Transform Infrared; Water; X-Ray Diffraction

Monomeric and epichlorohydrin polymerized β-CD functionalized monoliths were prepared for the rapid isolation and purification of the isoflavonoid puerarin, a well-known traditional Chinese drug, from a crude extract of Radix puerariae (root of the plant Pueraria lobata). Two copolymers poly(isocyanatoethyl methacrylate-co-methyl methacrylate-co-ethylene dimethacrylate) (poly(IEM-co-MMA-co-EDMA)) and poly(glycidyl methacrylate-co-EDMA) (poly(GMA-co-EDMA)) were developed as facile, highly reactive and versatile monolithic matrix. SEM characterization demonstrated that the modified monoliths had homogenous porous structure and morphology. The success of the chemical modification of the monolithic matrix was confirmed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), solid-state (13) C NMR and elemental analysis. It was demonstrated that polymeric β-CD modified monoliths had better separation and selectivity for puerarin, recovering puerarin with a purity of 96% (m%) and a yield of 93% (m%). Compared with poly(glycidyl methacrylate-co-EDMA), poly(isocyanatoethyl methacrylate-co-methyl methacrylate-co-EDMA) monolithic matrix had higher reactivity, which significantly improved the β-CD ligand density and thus the selectivity of the monoliths. Puerarin with a purity of 96% (m%) and with a yield of 89% (m%) was recovered on the monolith.

Topics: Adsorption; beta-Cyclodextrins; Chromatography, Liquid; Drugs, Chinese Herbal; Isoflavones; Plant Roots; Polymers; Pueraria

The poly(glycidyl methacrylate) adsorbents P(GMA-EDMA) and P(GMA-DVB) were synthesized by the radical suspension-polymerization method and farther coupled by oligo-beta-cyclodextrin (CDP) to obtain P(GMA-EDMA)-CDP and P(GMA-DVB)-CDP. The synthesized polymeric media were characterized by Fourier transform infrared (FTIR) spectrometer, scanning electron microscopy, and BET surface area. The adsorption of puerarin from aqueous solution onto the four media, i.e., P(GMA-EDMA), P(GMA-DVB), P(GMA-EDMA)-CDP, and P(GMA-DVB)-CDP, was studied. An enhanced adsorption of puerarin apparently presented on grafted media. The interaction between the polymeric media and the puerarin was researched by FTIR. The result shows that the adsorption efficiency on P(GMA-DVB)-CDP driven by multiple weak interactions is much higher than that on P(GMA-EDMA) driven by hydrogen bonding interaction only and on P(GMA-DVB) or P(GMA-EDMA)-CDP driven by two interactions.

Topics: Adsorption; beta-Cyclodextrins; Isoflavones; Polymethacrylic Acids; Surface Properties

Puerarin and daidzin, two major isoflavonoids of Radix puerariae , are widely adopted in traditional Chinese medicine. Foundational aspects related to separating the two compounds are essential to develop a more economical purification process. Inclusion models of the two compounds with beta-cyclodextrin (beta-CD) have been investigated by molecular dynamics simulation. Computational results reveal that both puerarin and daidzin can induce a conformational change of beta-CD, which is compressed in one direction and stretched in the other. The effect of solvent and media on the conformational change of beta-CD and the movement of guest molecules inside the cavity has been investigated. Furthermore, hydrogen bonding interactions have been analyzed, and the results have been utilized for the explanation of separating puerarin from daidzin.

Topics: beta-Cyclodextrins; Carcinogens; Enzyme Inhibitors; Hydrogen Bonding; Isoflavones; Models, Chemical; Models, Molecular; Molecular Dynamics Simulation; Molecular Structure; Vasodilator Agents

The purpose of this work is to develop poly(vinyl alcohol) (PVA) hydrogels incorporating large amounts of beta-cyclodextrin (beta-CD) in order to improve ocular drug loading and to sustain drug release. First, the mono-methacrylated-beta-CD monomer (MA-beta-CD) and the methacrylated-PVA macromer (PVAMA), with a substitution degree of 7%, are synthesized and characterized. Then, the poly(methacrylated-PVA-co-mono-methacrylated-beta-cyclodextrin) (pPVA-beta-CD) hydrogels are prepared by UV-induced polymerization of MA-beta-CD and PVAMA. The highest amount of beta-CD incorporated into the hydrogels is 30 wt%. The hydrogels are further characterized by transmittance, FT-IR, equilibrium swelling ratio (ESR), tensile tests and protein deposition. The results show that pPVA-beta-CD hydrogels possess good transmittance, while the incorporation of beta-CD in the hydrogels improves the tensile strength and decreases the ESR and protein deposition. Finally, puerarin and acetazolamide are used as models to evaluate the drug loading and in vitro release behavior of the pPVA-beta-CD hydrogels. The results indicate that the amount of drug loaded into the pPVA-beta-CD hydrogels progressively increases, while the release rate decreases with increasing beta-CD content. In particular, incorporation of beta-CD efficiently decreases the initial burst release of acetazolamide, while the release, which is almost linear, is sustained for 15 days. The pPVA-beta-CD hydrogels have potential applications as biomedical devices for sustained release of ocular drugs.

Topics: Acetazolamide; Adsorption; Animals; beta-Cyclodextrins; Cattle; Delayed-Action Preparations; Drug Carriers; Electron Spin Resonance Spectroscopy; Eye Diseases; Hydrogels; Isoflavones; Mechanical Phenomena; Methacrylates; Pharmaceutical Preparations; Phenol; Photochemical Processes; Polyvinyl Alcohol; Serum Albumin, Bovine; Spectroscopy, Fourier Transform Infrared; Sulfuric Acids; Ultraviolet Rays

To prepare a novel floating micropellets containing hydroxy propyl-beta-oyclodextrin(puerarin-HP-beta-CD) for gastroretentive dosage form and evaluate its pharmaceutical characteristics in vitro.. The puerarin HP-beta-cyclodextrin inclusion complex was prepared by freeze-drying method. Puerarin and its HP-beta-CD inclusion complex were incorporated into alginate beads, respectively. The effect of methyl cellulose (MC), Mg-Stearate and chitosan on buoyancy and cumulative release rate of puerarin were investigated in simulated gastric fluid.. The spectrums of FTIR and profiles of X-ray powder diffraction of samples proved the formation of inclusion complex between puerarin and HP-beta-CD. Magnesium stearate had a significant effect on the buoyancy of micropellets, and satisfied results were gained by the content with 2%. The solubility of puerarin was increased 65.6-fold by the formation of inclusion complex, the dissolution rate and cumulative release percentage also improved significantly although with the burst release phenomena. The micropellets showed sustained release properties by using puerarin-HP-beta-CD inclusion complex mixed with puerarin (1:1) and treated thoroughly under homogenizer.. The solubility and release rate of puerarin are increased by the formation of inclusion complex with HP-beta-CD and its gastroretentive dosage forms displayed satisfied floating and sustained release characteristics.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Dosage Forms; Freeze Drying; Isoflavones; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

The purpose of this study was to develop a pH-triggered in situ gelling vehicle for ophthalmic delivery of puerarin. The effect of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the aqueous solubility and in vitro corneal permeation of puerarin was also investigated. The puerarin solubility increased linearly and proportionally to the HP-beta-CD concentrations and 5% (w/v) HP-beta-CD enhanced its ocular permeability significantly. Carbopol 980NF was used as the gelling agent in combination with HPMC (Methocel E4M) which acted as a viscosity-enhancing agent. The optimum concentrations of Carbopol 980NF and HPMC E4M for the in situ gel-forming delivery systems were 0.1% (w/v) and 0.4% (w/v), respectively. When these two vehicles were combined, an in situ gel that had the appropriate gel strength and gelling capacity under physiological condition could be obtained. This combined solution could flow freely under non- physiological condition and showed the character of pseudoplastic fluid under both conditions. Both in vitro release studies and in vivo pharmacokinetics studies indicated that the combined polymer systems performed better in retaining puerarin than puerarin eye drops did. These results demonstrate that the Carbopol 980NF/HPMC E4M can be a viable alternative to conventional puerarin eye drops to enhance ocular bioavailability and patient compliance.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acrylic Resins; Animals; beta-Cyclodextrins; Biological Availability; Cell Membrane Permeability; Cornea; Drug Carriers; Drug Delivery Systems; Female; Gels; Hydrogen-Ion Concentration; Hypromellose Derivatives; In Vitro Techniques; Isoflavones; Male; Methylcellulose; Ophthalmic Solutions; Polymers; Polyvinyls; Rabbits; Solubility; Vasodilator Agents; Viscosity

The purpose of this study was to systematically optimize an ophthalmic thermosensitive poloxamer analogs gel containing puerarin that was a free flowing liquid below the room temperature and could shift to a gel with an eligible gel strength and bioadhesive force in physiological condition (dilution by the simulated tear fluid and at 35.0 degrees C). A two-factor, five-level central composite design (CCD) was employed to the optimization procedure. The effect of formulation variables (the w/v concentration of poloxamer 407 (X1) and poloxamer 188 (X2)) on a number of response variables (the gelation temperature before (Y1) and after (Y2) the simulated tear fluid diluted, the difference between them (Y3)) was systemically investigated. A second order polynomial equation was fitted to the data. The resulting equation and response surface plots were used to predict the responses in the optimal region. Finally, 21.0% (w/v) poloxamer 407 and 5.0% (w/v) poloxamer188 were chosen as the optimal poloxamer gel matrix. The influence of the other ingredients on the physicochemical properties of the formulation was also investigated. Hydroxypropyl-beta-cyclodextrin (HPCD) enhanced the gelation temperature and reduced the gel strength and the bioadhesive force, while puerarin and benzalkonium chloride (BC) had a comparatively smaller influence. All the isotonicity agents studied had the gelation temperatures lowered, and the gel strengths and the bioadhesive forces enhanced. But only sodium chloride appears to be a promising isotonicity agent for the poloxamer gel containing puerarin, HPCD and BC.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Benzalkonium Compounds; beta-Cyclodextrins; Chemical Phenomena; Chemistry, Physical; Gels; Isoflavones; Ophthalmic Solutions; Poloxamer; Temperature

The isoflavonoid puerarin, a well-known traditional Chinese drug, has been purified in one step from an extract of Radix puerariae (root of the plant Pueralria lobata) by adsorption chromatography on an epichlorohydrin polymerized beta-cyclodextrin ligand coupled to brominated allyl-group substituted Sepharose HP. Acetic acid (10%) was used as the mobile phase and the optimum loading capacity was around 1.2 mg crude extract/ml packed gel. The purity of the collected puerarin was about 98% with a recovery of about 62%.

Topics: beta-Cyclodextrins; Chromatography, High Pressure Liquid; Cyclodextrins; Isoflavones; Sepharose