Prevotella and succinate treatments altered gut microbiota,increased laying performance,and suppressed hepatic lipid accumulation in laying hens

Background This work aimed to investigate the potential benefits of administering Prevotella and its primary metabolite succinate on performance,hepatic lipid accumulation and gut microbiota in laying hens.Results One hundred and fifty 58-week-old Hyline Brown laying hens,with laying rate below 80%and plasma triglyceride(TG)exceeding 5 mmol/L,were used in this study.The hens were randomly allocated into 5 groups and subjected to one of the following treatments:fed with a basal diet(negative control,NC),oral gavage of 3 mL/hen saline every other day(positive control,PC),gavage of 3 mL/hen Prevotella melaninogenica(10^(7)CFU/mL,PM)or 3 mL/hen Prevotella copri(10^(7)CFU/mL,P.copri)every other day,and basal diet supplemented with 0.25%sodium succinate(Succinate).The results showed that PM and P.copri treatments significantly improved laying rate compared to the PC(P<0.05).The amount of lipid droplet was notably decreased by PM,P.copri,and Succinate treatments at week 4 and decreased by P.copri at week 8(P<0.05).Correspondingly,the plasma TG level in Succinate group was lower than that of PC(P<0.05).Hepatic TG content,however,was not significantly influenced at week 4 and 8(P>0.05).PM treatment increased(P<0.05)the mRNA levels of genes PGC-1βand APB-5B at week 4,and ACC and CPT-1 at week 8.The results indicated enhanced antioxidant activities at week 8,as evidenced by reduced hepatic malondialdehyde(MDA)level and improved antioxidant enzymes activities in PM and Succinate groups(P<0.05).Supplementing with Prevotella or succinate can alter the cecal microbiota.Specifically,the abundance of Prevotella in the Succinate group was significantly higher than that in the other 4 groups at the family and genus levels(P<0.05).Conclusions Oral intake of Prevotella and dietary supplementation of succinate can ameliorate lipid metabolism of laying hens.The beneficial effect of Prevotella is consistent across different species.The finding highlights that succinate,the primary metabolite of Prevotella,represents a more feasible feed additive for alleviating fatty liver in laying hens.

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid-to high-frequency sudden sensorineural hearing loss

BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.

Clinical Efficacy of Metoprolol Succinate Extended-Release Tablets in the Treatment of Post-Myocardial Infarction Ventricular Arrhythmias

Objective:To investigate the clinical efficacy of metoprolol succinate extended-release tablets in the treatment of post-myocardial infarction ventricular arrhythmias.Methods:The clinical data of 84 patients with post-myocardial infarction ventricular arrhythmia included in the study were collected and they were divided into Groups A and B with 42 cases each using the randomization method.Group A was treated with oral glucosamine hydrochloride,while Group B was administered oral metoprolol succinate extended-release tablets.Combined indicators were used to evaluate the improvement of clinical indicators,therapeutic effects,and the incidence of adverse reactions in the two groups.Results:The baseline data of the two groups of patients were not statistically significant(Pall>0.05);after treatment,the QT dispersion,corrected QT dispersion,and heart rate of Group B were lower than that of Group A(Pall=0.000<0.001);the 2 total clinical effectiveness of Group B was 95.24%,which was significantly higher than 80.95%in Group A(χ=4.087,P=0.043<0.05);the total incidence of adverse reactions in Group B was 4.76%,which was significantly lower than 219.04%in Group A(χ=4.087,P=0.043<0.05).Conclusion:In the treatment of post-myocardial infarction ventricular arrhythmia,the use of metoprolol succinate extended-release tablets can effectively correct the QT dispersion of patients,improve their heart rate,increase clinical effectiveness,and reduce the incidence of adverse reactions.

Ischemic accumulation of succinate induces Cdc42 succinylation and inhibits neural stem cell proliferation after cerebral ischemia/reperfusion

Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue(cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.

Influence of ganglioside combined with methylprednisolone sodium succinate on efficacy and neurological function in patients with acute myelitis

BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.

Insight into the green route to dimethyl succinate by direct esterification of bio-based disodium succinate using CO_(2)and CH_(3)OH

The fermentation for succinic acid production outperforms other methods by low energy consumption and environmental benignity,with the resulting products mainly as disodium succinate(DSA).By directly esterifying DSA using CO_(2) and CH3OH,it is expected to avoid the use of inorganic acids.By high-resolution mass spectrometry analysis and theoretical calculation,this study establishes that the reaction consists of three steps,i.e.,first forming 3-carboxypropanoate,then monomethyl succinate(MMS),and finally dimethyl succinate(DMS).A detailed kinetic analysis is further performed,the results demonstrate that the transformation of DSA to MMS is regarded to be a second-order reaction for reactant DSA,while the transformation of MMS to DMS is a first-order reaction for reactant MMS.The activation energy for the generation of MMS from DSA is 37.15 kJ·mol^(-1),and that for the generation of DMS from MMS is 85.80 kJ·mol^(-1),indicating the latter one is the rate-determining step.

Role of succinate dehydrogenase deficiency and oncometabolites in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.At the molecular level,GISTs can be categorized into two groups based on the causative oncogenic mutations.Approximately 85%of GISTs are caused by gain-of-function mutations in the tyrosine kinase receptor KIT or platelet-derived growth factor receptor alpha(PDGFRA).The remaining GISTs,referred to as wild-type(WT)GISTs,are often deficient in succinate dehydrogenase complex(SDH),a key metabolic enzyme complex in the tricarboxylic acid(TCA)cycle and electron transport chain.SDH deficiency leads to the accumulation of succinate,a metabolite produced by the TCA cycle.Succinate inhibitsα-ketoglutarate-dependent dioxygenase family enzymes,which comprise approximately 60 members and regulate key aspects of tumorigenesis such as DNA and histone demethylation,hypoxia responses,and m6A mRNA modification.For this reason,succinate and metabolites with similar structures,such as D-2-hydroxyglutarate and fumarate,are considered oncometabolites.In this article,we review recent advances in the understanding of how metabolic enzyme mutations and oncometabolites drive human cancer with an emphasis on SDH mutations and succinate in WT GISTs.

Comparsion of the Effects of Succinate and NADH on Postmortem Metmyoglobin Redcutase Activity and Beef Colour Stability

In two experiments, the effects of succinate and NADH（reduced nicotinamide adenine dinucleotide） on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and compared. In experiment 1, metmyoglobin（MetMb）, substrate and inhibitors were incubated with mitochondria. Comparsion of the effects of succinate and NADH on MetMb reduction was investigated. The MetMb percentage in sample treated with 8 mol L-1 succinate decreased by about 69% after 3 h incubation, and the effect was inhibited by the addition of 10 mol L-1 electron transfer chain complex II inhibitor malonic acid; the MetMb percentage in samples treated with 2 mol L-1 NADH decreased by 56% and the effect was inhibited by the addition of 0.02 mol L-1 electron transport chain complex I inhibitor rotenone. These results indicated that electron transport chain played an important role in MetMb reduction. Both complex II and complex I take part in the MetMb reduction in mitochondria through different pathways. NADH-MetMb reduction system was less stable than succinateMetMb system. In experiment 2, the beef longissimus dorsi muscle was blended with different concentrations of succinate or NADH. Enhancing patties with higher concentration of succinate or NADH improved colour stability in vacuum packaged samples（P〈0.05）. These results verified that mitochondria electron transport chain is related to the MetMb reduction in meat system.

Enzyme-catalyzed Synthesis of Vitamin E Succinate Using a Chemically Modified Novozym-435

Vitamin E succinate was synthesized in organic solvents using a modified Novozym-435 as catalyst.In order to improve the catalytic performance of Novozym-435,the enzyme was modified using acetic anhydride, propionic anhydride and succinic anhydride separately.We found that both the hydrolytic activity and the thermal stability of the modified Novozym-435 were enhanced compared with the unmodified enzyme.The modified Novozym-435 catalysts were used to synthesize the succinate derivative of vitamin E.Compared with the native Novozym-435,the catalytic activity of the modified novozym-435 in promoting the synthesis of vitamin E succinate was dramatically increased,with the novozym-435 modified with succinic anhydride（N435-S）as the most active catalyst.Conditions for the synthesis of vitamin E succinate were also optimized.A mixture of tert-butanol and DMSO（volume ratio of 2︰3）was the most suitable medium for the reaction,whereas the appropriate molar ratio of vitamin E to succinic anhydride and reaction temperature were 1︰5 and 40°C,respectively.Under these reaction conditions,the yield of vitamin E succinate reached 94.4%.N435-S could be reused for five batches.

Miscibility, Crystallization, and Rheological Behavior of Solution Casting Poly（3-hydroxybutyrate）/poly（ethylene succinate） Blends Probed by Differential Scanning Calorimetry, Rheology, and Optical Microscope Techniques

The miscibility and crystallization of solution casting biodegradable poly（3-hydroxybuty- rate）/poly（ethylene succinate） （PHB/PES） blends was investigated by differential scanning calorimetry, rheology, and optical microscopy. The blends showed two glass transition temperatures and a depression of melting temperature of PHB with compositions in phase diagram, which indicated that the blend was partially miscible. The morphology observation supported this result. It was found that the PHB and PES can crystallize simultaneously or upon stepwise depending on the crystallization temperatures and compositions. The spherulite growth rate of PHB increased with increasing of PES content. The influence of compositions on the spherulitic growth rate for the partially miscible polymer blends was discussed.

Succinate dehydrogenase-deficient gastrointestinal stromal tumors

Most gastrointestinal stromal tumors(GISTs)are characterized by KIT or platelet-derived growth factor alpha(PDGFRA)activating mutations.However,there are still 10%-15%of GISTs lacking KIT and PDGFRA mutations,called wild-type GISTs(WT GISTs).Among these so-called WT GISTs,a small subset is associated with succinate dehydrogenase(SDH)deficiency,known as SDH-deficient GISTs.In addition,GISTs that occur in Carney triad and Carney-Stratakis syndromerepresent specific examples of SDH-deficient GISTs.SDH-deficient GISTs locate exclusively in the stomach,showing predilection for children and young adults with female preponderance.The tumor generally pursues an indolent course and exhibits primary resistance to imatinib therapy in most cases.Loss of succinate dehydrogenase subunit B expression and overexpression of insulin-like growth factor 1 receptor(IGF1R)are common features of SDH-deficient GISTs.In WT GISTs without succinate dehydrogenase activity,upregulation of hypoxia-inducible factor 1αmay lead to increased growth signaling through IGF1R and vascular endothelial growth factor receptor(VEGFR).As a result,IGF1R and VEGFR are promising to be the novel therapeutic targets of GISTs.This review will update the current knowledge on characteristics of SDH-deficient GISTs and further discuss the possible mechanisms of tumorigenesis and clinical management of SDH-deficient GISTs.

Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice

BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications.

Increased succinate receptor GPR91 involved in the pathogenesis of Mooren's ulcer

AIM： To investigate the expression of succinate receptor GPR91 and its pathogenic roles in Mooren＇s ulcer（MU）.METHODS： Biopsy specimens were obtained from 7 patients with MU and 6 healthy donors. The expression of GPR91 in MU tissues was evaluated using quantitative realtime reverse transcription polymerase chain reaction（qRTPCR） and immunohistochemistry（IHC）. Succinate was used to activate GPR91 signaling, and the effect of GPR91 on the expression of interleukin-1β（IL-1β）, NLRP3, vascular endothelial growth factor（VEGF） and matrix metalloproteinase-13（MMP-13） in human peripheral blood mononuclear cells（PBMCs） was determined. The influence of GPR91 on the nuclear factor-κB（NF-κB） signaling in PBMCs was investigated by detecting the phosphorylation of p65. Moreover, the expression of IL-1β, VEGF, MMP-13 and phosphorylated p65（p-p65） in the tissues of MU was examined by qRT-PCR or IHC.RESULTS： GPR91 mRNA expression showed a higher level in the MU group than in the healthy control group. IHC analysis also revealed that the expression of GPR91 was elevated in patients with MU compared with healthy controls. Moreover, ligation of GPR91 with succinate promoted the lipopolysaccharide-induced production of NLRP3, IL-1β, VEGF and MMP-13 in PBMCs through increased phosphorylation of p65. Pharmacological inhibition of the NF-κB signaling reversed GPR91 induced production of NLRP3, IL-1β, VEGF and MMP-13. These findings, coupled with the elevated amounts of IL-1β, VEGF, MMP-13 and p-p65 observed in the MU biopsies, constituted a rational basis for the involvement of GPR91 in the pathogenesis of MU.CONCLUSION： This study indicates the increased succinate receptor GPR91 in conjunctival or corneal tissues is involved in the pathogenesis of MU through elevated NF-κB activity, which may provide a new therapeutic target for MU.

Recent Advances of D-α-tocopherol Polyethylene Glycol 1000 Succinate Based Stimuli-responsive Nanomedicine for Cancer Treatment

D-a-tocopherol polyethylene glycol 1000 succinate(TPGS)is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA.It's widely applied as a multifunctional drug carrier for nanomedicine.The advantages of TPGS include P-glycoprotein(P-gp)inhibition,penetration promotion,apoptosis induction via mitochondrial-associated apoptotic pathways,multidrug resistant(MDR)reversion,metastasis inhibition and so on.TPGS-based drug delivery systems which are responding to extermal stimulus can combine the inhibitory functions of TPGS towards P-gp with the environmentally responsive controlled release property and thus exerts a synergistic anti-cancer effect,through increased intracellular drug concentration in tumors cells and well-controlled drug release behavior.In this review,TPGS-based nano-sized delivery systems responsive to different stimuli were summarized and discussed,including pH-responsive,redox-responsive and multi-responsive systems in various formulations.The achievements,mechanisms and diffcrent characteristics of TPGS-bascd stimuli-responsive drug-delivery systems in tumor therapy were also outlined.

Enzymatic Degradation of Poly(butylenesuccinate)/Thermoplastic Starch Blend

The degradation of thermoplastic starch blend in the presence of commerciala-amylase and unpurified amylase of microbial origin was investigated.The blends consisting of thermoplastic starch and poly(butylene succinate)have potential use in packaging applications thus,it is essential to establish susceptibility to degradation.Molar mass loss,gravimetric weight loss,and molecular structure were evaluated.The changes in the surface were observed with scanning electron microscopy.It was confirmed that there was a significant difference in gravimetric weight loss between the blends degraded in two different solutions.Unpurified enzymes of microbial origin,produced by Rhizopus oryzae cultures decomposed analyzed materials more efficiently than purified commercial ones.Moreover,it was proved that in applied conditions,the molar mass of PBS fraction did not change significantly.

Crystal Structure and Luminescent Properties of a 3D Cd(Ⅱ) Compound Constructed from Succinate and 3,6-Di(4-pyridyl)pyridazine

A three-dimensional（3D） coordination polymer,[Cd（SC）（DPPD）]_n（1,H_2SC = succinic acid and DPPD = 3,6-di（4-pyridyl）pyridazine）,has been synthesized by the solvothermal reaction of Cd（NO_3）_2·4H_2O with H_2 SC and DPPD at 120 ℃ in DMF solvent. Compound 1 crystallizes in the monoclinic system,space group P2_1/c,with a = 10.7993（4）,b = 11.7705（3）,c = 13.5336（6） A,V = 1678.89（11） A^3,Z = 4,C18H14N4O_4 Cd,M_r = 462.73,D_c = 1.831 g/cm^3,μ = 1.335 mm^（-1）,F（000） = 920.0,the final R = 0.0500 and wR = 0.1567 for 3714 observed reflections with I 〉 2s（I）. In compound 1,the Cd（Ⅱ） ions are linked by the SC^2– ligands to give a two-dimensional（2D） undulating sheet based on the centrosymmetric dinuclear Cd_2（COO）_2 units. The 2D sheets are further connected by the DPPD ligands to produce a 3D structure,which is a 6-connected（4^4·6·^10·8） topological network based on the dinuclear Cd_2（COO）_2 node. Compound 1 exhibits a photoluminescent emission with a maximum at 540 nm upon excitation at 460 nm.

Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

Improving Polylactide Toughness by Plasticizing with Low Molecular Weight Polylactide-Poly(Butylene Succinate)Copolymer

A low-molecular-weight polylactide-poly(butylene succinate)(PLA-PBS)copolymer was synthesized and incorporated into polylactide(PLA)as a novel toughening agent by solvent casting.The copolymer had the same chemical structure and function as PLA and it was used as a plasticizer to PLA.The copolymer was blended with PLA at a weight ratio from 2 to 10 wt%.Phase separation between PLA and PLA-PBS was not observed from their scanning electron microscopy(SEM)images and the crystal structure of PLA almost remained unchanged based on the X-ray diffraction(XRD)measurement.The melt flow index(MFI)of the blends was higher as the amount of PLA-PBS increased,indicating that the block copolymer did improve the mobility of the PLA chains.Moreover,tensile tests revealed that PLA with greater PLA-PBS copolymer exhibited higher elongation at break and it reached the maximum at 8 wt%of PLA-PBS in PLA,which was around 6 times higher than that of pure PLA.Furthermore,the glass transition temperature,measured by differential scanning calorimetry(DSC),markedly decreased with an increasing amount of the copolymer as it decreased from 61.2℃ for pure PLA to 41.3℃when it was blended with 10 wt%PLA-PBS copolymer.Therefore,the PLA-PBS copolymer was shown to be a promising plasticizer for fully biobased and toughened PLA.

Liquid-Liquid Equilibria of the Water-Ethanol-Dimethyl Succinate Ternary System

Liquid-liquid equilibrium (LLE) data for the ternary systemwater-ethanol-dimethyl succinate have been determined experimentallyat temperatures ranging from 298.15 to 318.15 K at 5 K intervals.Complete phase diagrams were obtained by determining solubility andthe tie-line data. Tie-line compositions were correlated byOthmer-Tobias method. The universal quasichemical functional groupactivity coefficient (UNIFAC) and modified UNIFAC methods were usedto predict the phase equilibrium in the system using the interactionparameters deter- Mined from experimental data between groups CH_3,CH_2, OH, CH_3 COO and H_2O.

Preparation of Starch Succinate WITH INTERMEDIATE DS BY AQUEOUS SLURRY REACTION

The succinylation of cornstarch by slurry reaction has been studied using sodium hydroxide as catalyst. Several reaction parameters affecting the succinylation were investigated including the concentration of starch in water, the ratio of succinic anhydride to starch, the reaction time and the reaction temperature. The favorable conditions for an intermediate degree of substitution (DS) and reasonably high reaction efficiency (RE) are pH 8.5~9.0, 50% starch by weight to water, succinic anhydride to starch 1/1 (w/w), reaction time 4h, reaction temperature 30℃. Under these conditions, the DS of 0.45 and RE of 28% were achieved. The addition of an adequate amount of crosslinking agent imparted starch succinate water absorbency.