Inclusion complex of tamibarotene with hydroxypropyl-β-cyclodextrin: Preparation,characterization, in-vitro and in-vivo evaluation

The goal of this study was to improve the solubility and oral bioavailability of tamibarotene by complexing it with hydroxypropyl-β-cyclodextrin(HP-β-CD).The inclusion complex of tamibarotene with hydroxypropyl-β-cyclodextrin(Am80-HP-β-CD)was prepared through a freeze-drying method at the mole ratio of 1:1(Am80:HP-β-CD).Fourier transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC)indicated the formation of Am80-HP-β-CD.In vitro dissolution studies showed that the solubility and dissolution percentage of Am80-HP-β-CD was improved substantially compared to Am80.An improved dissolution with approximately 97%drug release in 3 min was observed,in comparison with Am80 with approximately 60% release in 45 min.In vivo studies indicated that the AUC0-∞ has increased 2.79 times and the Cmax 4.37 times after the formation of inclusion complex.The decrease of tmaxindicated the Am80-HP-β-CD inclusion complex can be absorbed into blood faster.In short,the solubility and bio-availability of Am80 has notably increased with the complexation of HP-β-CD.Therefore,using the inclusion technique is a promising method to improve the solubility of insoluble drugs.

ADSORPTION OF 1,2,4-ACID BY WEAKLY BASIC RESIN: ISOTHERMS, THERMODYNAMICS AND KINETICS

The adsorption properties, including the adsorption isotherms, thermodynamics and kinetics, of 1-amino-2- naphthol-4-sulfonic acid (1,2,4-acid) onto weakly basic resin ND900 are investigated. Both the Langmuir and Freundlich equations can give a good fit to the adsorption isotherms, which indicates an endothermic and a favorable adsorption in our study range. A high yield in elimination of about 45.21 %-97.28% is obtained for the tested adsorption systems. The capacity and affinity of the adsorption increase with temperature, due to the phenomena of 'solvent-motivated' effects. The value of is 51.59 kJ/mol, which indicates a chemical adsorption and then expects the poor desorption property of ND900. The negative value of indicates the spontaneous nature of the adsorption process, and the positive value of shows the increased randomness at the solid/solution interface during the adsorption process. The value of the adsorption rate constant lower than 0.013 min-1 is indicative of a slow adsorption rate. The intra-particle diffusion must be one of the rate limiting steps.

THEATMENT OF WASTEWATER FROM PRODUCTION PROCESS OF 2,3-ACID

Wastewater from production process of 2,3-acid was treated by adsorption usingmacroporous resin NDA-708. After only one-step treatment by resin adsorption, removalefficiency of three kinds of naphthalene chemicals was above 99%, removal efficiency ofCODcr was above 96% Under proper operating condition, desorption efficiency wasaround 100%. The running records of the industrial facility showed that the naphthlenechemicals in desorption effluent could be reused without obvious influence on the qualityOf the product.

Synthesis of Hydroxypropyl-β-cyclodextrin Bonded Silica-gel and its Application to Resolution

In order to set up a simple and effective method for resolution of optical isomers, hydroxypropyl-β-cyclodextrin was bonded to silica-gel, which can be used for preparation of thin-layer chromatography plates. Resolution of clenbuterol and propranolol were investigated on these thin-layer chromatography plates using different combinations of solvent systems at ambient temperature. The best simultaneous resolution was achieved in solvent system of acetonitrilen-butanol （50：50, v/v）. Rst values of resolution of clenbuterol hydrochloride and propranolol hydrochloride are 3.6 and 4.3, respectively. The spots of different enantiomers are separated clearly. The results showed that hydroxypropyl-β-cyclodextrin bonded silica-gel could be successful in resolution of chiral adrenergic drugs. The study offers a direct, rapid and reliable method for separation of this kind of optically active compounds.

Preparation and Evaluation of Insulin-loaded Nanoparticles based on Hydroxypropyl-β-cyclodextrin Modified Carboxymethyl Chitosan for Oral Delivery

Novel insulin-loaded nanoparticles based on hydroxypropyl-β-cyclodextrin modified carboxymethyl chitosan（CMC-HP-β-CD） were prepared to improve the oral bioavailability of insulin. The CMC-HP-β-CD was characterized by FT-IR spectroscopy and 1H-NMR spectra. The insulin-loaded nanoparticles were prepared through crosslinking with calcium ions, and the morphology and size of the prepared nanoparticles were characterized by transmission electron microscopy（TEM） and dynamic light scattering（DLS）. Cumulative release in vitro study was performed respectively in simulated gastric medium fluid（SGF, p H=1.2）, simulated intestinal fluid（SIF, p H=6.8） and simulated colonic fluid（SCF, p H=7.4）. The encapsulation efficiency of insulin was up to 87.14 ± 4.32% through high-performance liquid chromatography（HPLC）. Statistics indicated that only 15% of the encapsulated insulin was released from the CMC-HP-β-CD nanoparticles in 36 h in SGF, and about 50% of the insulin could be released from the nanoparticles in SIF, whereas more than 80% was released in SCF. In addition, the solution containing insulin nanoparticles could effectively reduce the blood glucose level of diabetic mice. The cytotoxicity test showed that the samples had no cytotoxicity. CMC-HP-β-CD nanoparticles are promising candidates as potential carriers in oral insulin delivery systems.

Study on Brewing Characteristics of High α-acid and High β-acid Hops

[Objectives] Columbus and Tsingtao Flower were selected to brew Ale beer, thereby studying the brewing characteristics of high α-acid and high β-acid content hops. [Methods] The content of diacetyl and bitterness in beer were determined by a spectrophotometer at 335 and 275 nm, respectively. With pH=8.2 as the end point of potentiometric titration, the total acid content in beer was calculated by acid-base titration method, and sensory evaluation for beer was conducted. [Results] The results show that α-acid is an important factor affecting the production and reduction rate of diacetyl in beer. The production and reduction rate of diacetyl in high α-acid hops were lower than those in high β-acid hops; iso-α-acid was the main source of bitterness in beer, and high α-acid hops had more significant bitter value than high β-acid hops; and malt acid compounds and fermentation production were the main source of total acid in beer, and high α-acid and high β-acid hops had a little effect on total acid in beer. In sensory evaluation, high α-acid hops were more effective than high β-acid hops in terms of zest of the mouthfeel, foaming retention and alcohol fragrance, while in clarity, high α-acid hops were lower than high β-acid hops. [Conclusions] Therefore, we can draw a conclusion that the brewing characteristics of high α-acid hops are better than those of high β-acid hops.

Preparation of Forsythiaside-hydroxypropyl-β-cyclodextrin Inclusion Complex and Its Characters

To overcome the chemical instability of forsythiaside,the forsythiaside-hydroxypropyl-β-cyclodextrin inclusion complex was prepared by triturating. The inclusion complex was found having a varied UV spectrum and melt temperature point. Inclusion complex has a higher stability to UV light and temperature over forythiaside itself. Pharmacological evidence showed that inclusion complex has little effect on pharmacokinetics by chicken intravenous injection. This study is favorable for developing preparations for forsythiaside and its clinical application.

Preparation,Characterization and Antioxidant Activity of Inclusion Complex of Bakuchiol with Hydroxypropyl-β-cyclodextrin

Bakuchiol isolated from Psoralea corylifolia is a naturally occurring prenylated phenolic monoterpene with a variety of bioactivities.The aim of this study was to improve the water solubility and thermal stability of bakuchiol through complexing it with hydroxypropyl-β-cyclodextrin(HP-β-CD).The bakuchiol/HP-β-CD inclusion complex's behavior and characterization were investigated by ultraviolet-visible(UV-vis)spectroscopy,Fourier transform infrared spectroscopy(FT-IR),thermogravimetric analysis(TGA),X-ray diffraction(XRD),1H nuclear magnetic resonance(NMR),and two-dimensional(2D)NMR.The obtained results indicated the formation of 1∶1 inclusion complex for bakuchiol with HP-β-CD.Water solubility of bakuchiol was significantly improved by complexation with HP-β-CD as demonstrated by phase solubility studies.The encapsulation of bakuchiol was confirmed by UV-vis,FT-IR,and XRD.The thermal stability was effectively enhanced by TGA and derivative thermogravimetry(DTG)analysis.In vitro antioxidant activity showed that bakuchiol/HP-β-CD inclusion complex had a little higher antioxidant ability than free bakuchiol.Moreover,we got the possible inclusion mode for the bakuchiol/HP-β-CD inclusion complex through NMR analysis.These results suggest that the inclusion complex can be a potentially useful approach in the design of novel formulations of bakuchiol for medical applications.

Solubility Enhancement of Domperidone Fast Disintegrating Tablet Using Hydroxypropyl-<i>β</i>-Cyclodextrin by Inclusion Complexation Technique

Domperidone Maleate (DOM), an antiemetic drug, has been used in treatment of adults and children. It has low aqueous solubility and hence low bioavailability. In present study, an attempt has been made to enhance the solubility of DOM by inclusion complexation with Hydroxypropyl-β-Cyclodextrin (HP-β-CD) using kneading technique and formulation of fast disintegrating tablets by using Sodium Starch Glycolate as superdisintegrant. Solubility analysis of DOM in different concentrations of HP-β-CD was carried out. Design of experiment (DOE) is done by using MINITAB 15.1 software to find out the variable for dissolution and disintegration time. HP-β-CD and SSG were identified as the variable for disintegration time and dissolution. For optimization of the concentration of HP-β-CD and SSG, two factors at two levels design through central composite design (CCD) were used which gave 13 formulations. All formulations are evaluated for characteristics such as weight variation, hardness, friability, disintegration time and dissolution of drug. Solubility of DOM increases linearly with increase in concentration of HP-β-CD. The optimum concentration of HP-β-CD is found to be in 1:2 molar ratios and SSG of 7%. The In-Vitro dissolution studies of optimized formulation and market sample were carried out in USP type II apparatus at different time intervals of 5, 10, 15 and 30 minutes at 50 rpm in 0.1 N HCl. The dissolution and disintegration time of optimized formulation is found better than market sample.

Water-Based Environmentally Friendly Pesticide Formulations Based on Cyclodextrin/Pesticide Loading System

Difenoconazole(DIF)is a representative variety of broad-spectrum triazole fungicides and liposoluble pesticides.However,the water solubility of DIF is so poor that its application is limited in plant protection.In addition,the conventional formulations of DIF always contain abundant organic solvents,which may cause pollution of the environment.In this study,two DIF/cyclodextrins(CDs)inclusion complexes(ICs)were successfully prepared,which were DIF/β-CD IC and DIF/hydroxypropyl-β-CD IC(DIF/HP-β-CD IC).The effect of cyclodextrins on the water solubility and the antifungal effect of liposoluble DIF pesticide were investigated.According to the phase solubility test,the molar ratio and apparent stability constant of ICs were obtained.Fourier transform infrared spectroscopy,thermal gravity analysis,X-ray diffraction and scanning electron microscopy were used systematically to characterize the formation and characteristics of ICs.The results noted that DIF successfully entered the cavities of two CDs.In addition,the antifungal effect test proved the better performance of DIF/HP-β-CD IC,which exceeded that of DIF emulsifiable concentrate.Therefore,our study provides informative direction for the intelligent use of liposoluble pesticides with cyclodextrins to develop water-based environmentally friendly formulations.

Preparation and Physicochemical Characterization of Quercetin-HP-β-CD Inclusion Complexes

Aim To prepare and characterize the QURC-HP-β-CD inclusion complexes and investigate the thermodynamic parameters of the process. Methods QURC-HP-β-CD inclusion complexes were prepared by the grinding method. The equilibrium inclusion constants and thermodynamic parameters were determinated by phase solubility analysis. Dissolution tests were performed to study the dissolution rate of inclusion complexes. The formation of inclusion complexes was confirmed by differential scanning calorimetry （ DSC）, infrared spectroscopy （IR） , powder X-ray diffractometry （PXRD） and scanning electron microscopy （SEM）. Results The aqueous solubility of quercetin was greatly increased （ about 37 folds） by inclusion technique, and the initial dissolution rate was markedly improved （10 folds） in the first 5 min. The results of DSC and SEM photographs showed that quercetin crystal disappeared in inclusion complexes, which indicated the formation of new phase. FT-IR spectra showed that the carbonyl quercetin crystal grinding method. absorption band of quercetin was shifted. PXRD showed that the diffraction peak of disappeared. Conclusion QURC-HP-β-CD inclusion complexes are produced by the The solubility of quercetin is improved by the inclusion technique.

Multicomponent cyclodextrin system for improvement of solubility and dissolution rate of poorly water soluble drug

The purpose of the present study was to investigate the interaction of Cinnarizine(CIN)with Hydroxypropyl-β-Cyclodextrin(HPβCD)in the presence of Hydroxy Acids(HA).Various binary and ternary systems of CIN with HPβCD and HA were prepared by kneading and coevaporation methods.For the ternary systems,HA were tried in three different concentrations.The interaction in solution phase was studied in detail by the phase solubility method,and the solid phase interactions were characterized by Fourier Transform Infrared(FTIR)spectroscopy,Differential Scanning Calorimetry(DSC),X-Ray Diffractometry(XRD),Scanning Electron Microscopy(SEM)and Proton Nuclear Magnetic Resonance(^1H-NMR).Phase solubility revealed the positive effect of HA on the complexation of CIN with HPβCD.Solid phase characterization confirmed the formation of inclusion complex in the ternary systems.Solubility and dissolution studies illustrated that out of three different concentrations tried,HA were most effective at the 1 M concentration level.Ternary systems were very effective in improving the solubility as well as dissolution profile of CIN than the CIN–HPβCD binary systems.FTIR,^1H-NMR and Molecular docking studies gave some insight at molecular level that actually which part of CIN was interacting with the HPβCD.Molecular docking and free energy calculation even enlighten the role of tartaric acid in increasing solubility of CIN in the ternary system.

Enantiomeric separation of phenylsuccinic acid by cyclodextrin-modified reversed phase high-performance liquid chromatography

The chiral separation of phenylsuccinic acid(PSA)was studied by reversed phase high-performance liquid chromatography(RP-HPLC)with cyclodextrins(CDs)as chiral mobile phase additives.The effects of types of CDs,concentration of hydroxypropyl-β-cyclodextrin(HP-β-CD),percentage of organic modifier,pH value and column temperature on enantioselective separation were investigated.The quantification property of the developed RP-HPLC method was examined.The chiral recognition mechanism of PSA was also discussed.The results show that a baseline separation of PSA enantiomers is achieved on a Lichrospher C18 column(4.6 mm(inner diameter)×250 mm,5μm)with HP-β-CD as chiral mobile phase additive.The capacity factors of R-PSA and S-PSA are 3.94 and 4.80,respectively.The separation factor and resolution are respectively 1.22 and 8.03.The mobile phase is a mixture of acetonitrile and deionized water(20-80,volume ratio)containing 10 mmol/L HP-β-CD and 0.05% trifluoroacetic acid(pH 2.5,adjusted with triethylamine)with a flow rate of 1.0 mL/min.The ultraviolet(UV)detector is set at 254 nm.The likely roles are inclusion interaction,induction and hydrogen bonding between HP-β-CD and PSA enantiomers.

肉桂精油纳米乳液的抑菌性和稳定性研究

为改善精油的稳定性及抑菌性能,利用羟丙基-β-环糊精(HPCD)与酪蛋白酸钠(SC)共同乳化肉桂精油(CEO)制备纳米乳液,探究乳液的粒径、抑菌性的变化及乳液在不同温度下的储存稳定性。结果表明,相比单独使用酪蛋白酸钠稳定的乳液,HPCD的添加可以显著降低酪蛋白酸钠-精油乳液的粒径及PDI值。1%酪蛋白酸钠和3%HPCD共同稳定的肉桂精油纳米乳液对大肠杆菌和金黄色葡萄球菌的生长有良好的抑制作用,当精油添加量为10%时,大肠杆菌浓度降低了2.62 lg(CFU/mL),金黄色葡萄球菌浓度降低了0.85 lg(CFU/mL);乳液在4、25、40℃下储存过程中的粒径、乳化指数的变化表明,1%酪蛋白酸钠和3%HPCD共同乳化的肉桂精油纳米乳液具备良好的稳定性。当精油体积分数为10%时,乳液的粒径、乳化指数随着储藏时间的延长有所增加,但荧光显微镜显示乳液中油滴仍然分布相对均匀。

The efficacy of topical spray containing Centella asiatica extract on excision wound healing in rats

Centella asiatica (Linn.) belongs to the family of Apiaceae(Umbeliferae). It has been widely used for traditional medicine, especially for wound healing, anti-inflammatory,antipsoriatic, antiulcer, antibacterial and antifungal. The biologically active ingredients of Centella asiatica are believed to be triterpenes, particularly asiatic acid, madecassic acid,asiaticoside and madecassoside (Fig. 1).

Orosomucoid in liver diseases

In this editorial,the roles of orosomucoid(ORM)in the diagnoses and follow-up assessments of both nonneoplastic diseases and liver tumors are discussed with respect to the publication by Zhu et al presented in the previous issue of World Journal of Gastroenterology(2020;26(8):840-817).ORM,or alpha-1 acid glycoprotein(AGP),is an acute-phase protein that constitutes 1%to 3%of plasma proteins in humans and is mainly synthesized in the liver.ORM exists in serum as two variants:ORM1 and ORM2.Although the variants share 89.6%sequence identity and have similar biological properties,ORM1 constitutes the main component of serum ORM.An interesting feature of ORM is that its biological effects differ according to variations in glycosylation patterns.This variable feature makes ORM an attractive target for diagnosing and monitoring many diseases,including those of the liver.Recent findings suggest that a sharp decrease in ORM level is an important marker for HBV-associated acute liver failure(ALF),and ORM1 plays an important role in liver regeneration.In viral hepatitis,increases in both ORM and its fucosylated forms and the correlation of these increases with fibrosis progression suggest that this glycoprotein can be used with other markers as a noninvasive method in the follow-up assessment of diseases.In addition,similar findings regarding the level of the asialylated form of ORM,called asialo-AGP(AsAGP),have been reported in a follow-up assessment of fibrosis in chronic liver disease.An increase in ORM in serum has also been shown to improve hepatocellular carcinoma(HCC)diagnosis performance when combined with other markers.In addition,determination of the ORM level has been useful in the diagnosis of HCC with AFP concentrations less than 500 ng/mL.For monitoring patients with AFP-negative HCC,a unique trifucosylated tetra-antennary glycan of ORM may also be used as a new potential marker.The fact that there are very few studies investigating the expression of this glycoprotein and its variants in liver tissues constitutes a potential limitation,especially in terms of revealing all the effects of ORM on carcinogenesis and tumor behavior.Current findings indicate that ORM2 expression is decreased in tumors,and this is related to the aggressive course of the disease.Parallel to this finding,in HCC cell lines,ORM2 decreases HCC cell migration and invasion,supporting reports of its tumor suppressor role.In conclusion,the levels of ORM and its different glycosylated variants are promising additional biomarkers for identifying ALF,for monitoring fibrosis in viral hepatitis,and for diagnosing early HCC.Although there is evidence that the loss of ORM2 expression in HCC is associated with poor prognosis,further studies are needed to support these findings.Additionally,investigations of ORM expression in borderline dysplastic nodules and hepatocellular adenomas,which pose diagnostic problems in the differential diagnosis of HCC,especially in biopsy samples,may shed light on whether ORM can be used in histopathological differential diagnosis.

TREATMENT AND RESOURCE REUSE OF WASTEWATER FROM NAPHTHOL AS-E PRODUCTION PROCESS

The wastewater from naphthol As-E production process was treated with macroporous polymeric adsorbent NDA-222. Naphthol As-E and 2,3-acid in the wastewater could be removed completely and the Total Organic Carbon (TOC) of the wastewater was decreased more than 98% from 1655mg/L to less than 30mg/L. The adsorbates could be desorbed completely with NaOH aqueous solution.

Examination of Subunit Composition of Bombyx Mori Silk Fibroin

Main subunits of the silk fibroin were separated by GFC(gel filtration chromatography)technigue.The nativesilk fibroin and α,c subunits were measured by gel elec-trophoresis.The aminoacid compositions of the nativesilk fibroin and α,c subunits were analyzed by means ofaminoacid measurement.Some properties of silk was inter-preted in view of subunit composition of silk fibroin.

Pharmacokinetics of Eb and its hydroxypropyl-β-cyclodextrin inclusion complex in rats

In our previous study,a novel organic selenium compound Eb was synthesized and found to have significant antitumor activity with much less toxicity compared with the leading compound Ebselen.Unfortunately,Eb was practically insoluble in water （2.57 μg/mL） and had very low oral bioavailability,thus its clinical application was greatly limited.In the present study,the inclusion complex of Eb with 2-hydroxypropyl-β-cyclodextrin （HP-βCD） was prepared and pharmacokinetics of Eb and the inclusion complex were investigated.The water solubility of Eb was dramatically enhanced by inclusion with HP-βCD,which reached 8.4 mg/mL.The pharmacokinetic study showed that the elimination half-life （t 1/2β） of Eb was between 22 h and 30 h and the distribution half-life （t 1/2α） of Eb was 1 h.The results indicated that Eb was rapidly distributed to tissues but slowly eliminated in rats.The absolute bioavailability of Eb/HP-βCD inclusion complex solution through the oral route was 28.3%,and it was 1552% that of Eb in its pure form.In summary,the absorption of Eb in the Eb/HP-βCD inclusion complex was better and faster than that of Eb in its pure form.

Preparation of Hydroxypropyl-β-cyclodextrin Cross-linked Multi-walled Carbon Nanotubes and Their Application in Enantioseparation of Clenbuterol

A method of cross-linking multi-walled carbon nanotubes by a nucleophilic substitution of brominated multi-walled carbon nanotubes using hydroxypropyl-β-cyclodextrin anions was studied. The modified multi-walled carbon nanotube samples were characterized using thermogravimetric analysis, energy-dispersive X-ray spectroscopy, transmission electron microscopy, scanning electron microscopy, Raman spectroscopy and Fourier transform infrared spectroscopy. The hydroxypropyl-β-cyclodextrin modified multi-walled carbon nanotubes were used as a chiral stationary phase additive for thin-layer chromatography to separate clenbuterol enantiomers, and the chiral separation factor was increased.