Design, synthesis and in vitro evaluation of L-amino acid esters prodrugs of acyclic nucleoside phosphonates as anti-HBV agent

A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.

Folic Acid-Functionalized Nanocrystalline Cellulose as a Renewable and Biocompatible Nanomaterial for Cancer-Targeting Nanoparticles

The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functionalized NCCs were synthesized through a series of chemical reactions,resulting in nanoparticles with favorable properties for biomedical applications.The microstructural analysis revealed that the functionalized NCCs maintained their rod-shaped morphology and displayed hydrodynamic diameters suitable for evading the mononuclear phagocytic system while being large enough to target tumor tissues.Importantly,these nanoparticles possessed a negative surface charge,enhancing their stability and repelling potential aggregation.The binding specificity of FA-functionalized NCCs to folate receptor-positive cancer cells was demonstrated through various assays.The free folic acid inhibition assay showed approximately 30%decrease in the binding of functionalized NCCs in the presence of just 5 mM free FA,confirming their selectivity for folate receptor-positive cells.Confocal microscopy further validated this specificity,as only cancer cells displayed significant binding of functionalized NCCs.Crucially,biocompatibility tests revealed that both NCCs and FA-functionalized NCCs had minimal effects on red blood cells,and they did not induce erythrocyte aggregation.Furthermore,cell viability assays demonstrated functionalized NCCs have selective cytotoxicity against colorectal cancer cells HT-29 and SW-620(68%–88%cell viability)while sparing noncancerous colon cells CCD-18Co(81%–97%cell viability).In summary,FA-functionalized NCCs exhibit promising characteristics for targeted drug delivery in cancer therapy.Their biocompatibility,stability,and selective cytotoxicity make them an attractive option for delivering therapeutic agents to folate receptor-positive cancer cells,potentially improving the effectiveness of cancer treatments while minimizing harm to healthy tissues.

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Syntheses of Nucleoside Derivatives Containing Fmocor Trityl-protected Amino Acids

Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids %via% N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactions offer a mild and convenient method to synthesize aminoacylated nucleoside derivatives.

Interaction between N-Phospho-Amino Acids and Nucleoside in Aqueous Medium

Nucleosides were phosphorylated with different N- (O, O-diisopropyl) phosphoryl amino acids to give nucleoside mono phosphates in aqueous solution. 2', 3', and 5'-isomers had been confirmed by comparison with authentic samples on the basis of HPLC analysis. The conversion percentage of nucleoside indicated that N- (O, O-diisopropyl) phosphoryl aspartic acid reacted with adenosine and guanosine at a much higher rate than other kinds of N- phosphoryl amino acids. while phosphorylation of cytidine and uridine was relatively easy by using N- (O, O-diisopropyl) phosphoryl threonine. The result could give some clue to the prebiotic code origin of nucleic acid and protein.

Interaction between N-phosphoryl-α-,β-and γ-amino acids and nucleosides

The reactions of four different N-（O,O＇-diisopropyl） phosphoamino acids （DIPP-aa）, such as N-phosphoryl-L-α-alanine （DIPP- L-α-Ala）, N-phosphoryl-D-α-alanine （DIPP-D-α-A1a）, N-phosphoryl-β-alanine （DIPP-β-A1a） and N-phosphoryl-γ-amino butyric acid （DIPP-γ-Aba）, and four nucleosides, adenosine （A）, guanosine （G）, cytidine （C） and uridine （U）, were studied by electrospray ionization tandem mass spectrometry （ESI-MS/MS） and HPLC/ESI-MS. DIPP-L-α-A1a and DIPP-D-α-A1a produced the same phosphorylated nucleosides, dinucleotides and phosphoroligopeptide. However, DIPP-β-A1a and DIPP-γ-Aba gave no relevant products.

Clinical efficacy and safety of TCM prescriptions combined with nucleoside(acid)analogues in treating chronic hepatitis B:a meta-analysis

Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.

Risk of fracture and pneumonia from acid suppressive drugs

A recently published systematic review and meta-analy-sis, incorporating all relevant studies on the association of acid suppressive medications and pneumonia identi-fied up to August 2009, revealed that for every 200 patients, treated with acid suppressive medication, one will develop pneumonia. They showed the overall risk of pneumonia was higher among people using proton pump inhibitors （PPIs） [adjusted odds ratio （OR） = 1.27, 95% CI： 1.11-1.46, I2 = 90.5%] and Histamine-2 re-ceptor antagonists （H2RAs） （adjusted OR = 1.22, 95% CI： 1.09-1.36, I2 = 0.0%）. In the randomized controlled trials, use of H2RAs was associated with an elevated risk of hospital-acquired pneumonia （relative risk 1.22, 95% CI： 1.01-1.48, I2 = 30.6%）. Another meta-analysis of 11 studies published between 1997 and 2011 found that PPIs, which reduce stomach acid production, were associated with increased risk of fracture. The pooled OR for fracture was 1.29 （95% CI： 1.18-1.41） with use of PPIs and 1.10 （95% CI： 0.99-1.23） with use of H2RAs, when compared with non-use of the respective medications. Long-term use of PPIs increased the risk of any fracture （adjusted OR = 1.30, 95% CI： 1.15-1.48） and of hip fracture risk （adjusted OR = 1.34, 95% CI： 1.09-1.66）, whereas long-term H2RA use was not sig-nifcantly associated with fracture risk. Clinicians should carefully consider when deciding to prescribe acid-sup-pressive drugs, especially for patients who are already at risk for pneumonia and fracture. Since it is unneces-sary to achieve an achlorhydric state in order to resolve symptoms, we recommend using the only minimum effective dose of drug required to achieve the desired therapeutic goals.

Effect of Micelle Composition on Acidic Drugs Separation Behavior by Micellar Electrokinetic Capillary Chromatography

Micellar electrokinetic capillary chromatography (MECC) separation of four acidic drugs similar in structure was studied. Both anionic surfactant sodium dodecyl sulfate (SDS) and nonionic surfactant Tween 20 were used to form single micelles and mixed micelles as pseudostationary phases. The effects of the composition of micellar solution on retention behaviors were studied. The results indicate that there is markedly different selectivity among SDS, Tween 20 and the mixed micelles systems.

γ-aminobutyric acid B2 receptor:A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus

BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)conditions.Roles of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains unclarified.AIM To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.METHODS CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,respectively.GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot.Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence.GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis.Effects of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays.Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western blot.RESULTS GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent manner.CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.05).HG cells of both tested CCA cell lines were more sensitive to baclofen treatment.Baclofen significantly suppressed the proliferation and clonogenicity of CCA cells in both NG and HG conditions(P<0.05).Phospho-kinase arrays suggested glycogen synthase kinase 3(GSK3),β-catenin,and the signal transducer and activator of transcription 3(STAT3)as candidate signaling molecules under the regulation of GABBR2,which were verified in NG and HG cells of the individual CCA cell lines.Cyclin D1 and c-Myc,the common downstream targets of GSK3/β-catenin and STAT3 involving cell proliferation,were accordingly downregulated after baclofen treatment.CONCLUSION GABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition.

LYSOPHOSPHATIDIC ACID ACTIVATES NUCLEAR NUCLEOSIDE TRIPHOSPHATASE IN RAT HEPATOCYTES

Objectives.To observe if lysophosphatidic acid(LPA)can influence nuclear nucleoside triphos-phatase(NTPase)activity of isolated hepatocyte from rat,and to investigate the possible mechanisms by which LPA affects the NTPase.Method.Isolated and cultured hepatocytes from rat liver were exposed to LPA(1×10 -9 ,1×10 -8 and5×10 -8 mol/L)with or without inhibitors of protein kinase C(PKC)and mitogen activating protein kinase kinase(MAPKK),and the NTPase activity on nuclear envelope was assayed using ATP and GTP as substrate,respectively.Results.Nuclear NTPase activity of rat hepatocytes was potently stimulated by incubation of hepato-cytes with LPA in concentration?and time ?dependent manners.In hepatocytes incubated with LPA,nu-clear NTPase activity was significantly higher than that of the control(P<0.01).In hepatocytes preincu-bated with PKC inhibitor H-7or MAPKK inhibitor PD98059,LPA-stimulated activation of nuclear NT-Pase was obviously attenuated.In addition,direct incubation of isolated hepatic nuclei with LPA had no effect on nuclear NTPase activity.Conclusion.LPA is involved in modulating nuclear NTPase activity in hepatocytes.The stimulating effect of LPA on the nuclear NTPase is mediated at least partly by PKC and MAPK-dependent pathway.

Efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs against recurrent genital herpes:a systematic review and meta-analysis

Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of Science,Cochrane Library,Chinese Biomedical Literature Database,China National Knowledge Internet,VIP Database,and Wanfang Data were searched from inception to April 2021.Randomized controlled trials on the efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs for recurrent genital herpes were collected.All included trials were independently assessed by two reviewers with the Cochrane risk-of-bias tool,and a meta-analysis was conducted using Review Manager 5.4.Results:Compared with the use of nucleoside antiviral drugs alone,combination therapy with oral Chinese herbal medicine plus nucleoside antiviral drugs effectively reduced the herpes recurrence rate after the end of treatment(3 months:P=0.0002;6 months:P<0.00001;1 year:P<0.00001)and the number of recurrences each year(P<0.00001),improved the recurrent Genital Herpes Quality of Life Questionnaire score(P<0.00001),and regulated the levels of interferon-γ,interleukin-2,tumor necrosis factor-α,and T lymphocyte subsets in the peripheral blood,and the difference was statistically significant.Different subgroups reported mixed results with respect to the efficacy in the short term.The incidence of adverse reactions and the time of symptom disappearance between the two groups were not significantly different.Conclusion:Chinese herbal medicine combined with nucleoside antiviral drugs can effectively reduce the recurrence rate of recurrent genital herpes,improve the patient’s quality of life and enhance the body’s immunity.Considering the possible risk of publication bias,more high-quality randomized controlled trials are still needed to verify the conclusions of this article.

Effects of Fuzheng Huayu Capsules combined with nucleoside antiviral drugs on liver and kidney function, serum inflammatory factors, TLR-4, TGF-β1 and aspartate aminotransferase-platelet ratio index in patients with HBV infection and decompensated liver

Objective:To investigate the effect of Fuzheng Huayu Capsule combined with nucleoside antiviral drugs on liver and kidney function,serum inflammatory factors,Toll-like receptor 4(TLR-4),transforming growth factorβ1(TGF-β1)And aspartate aminotransferase-platelet ratio index(APRI).Methods:A total of 144 patients with HBV infection and decompensated cirrhosis were selected.All patients were divided into control group and case group by random number table method,with 72 cases in each group.The control group was given conventional liver protection and antiviral therapy;the case group was supplemented with Fuzheng Huayu Capsule on the basis of treatment in the control group.The changes of liver and kidney function,serum inflammatory factors,TLR-4,TGF-β1 and APRI in the two groups were observed.Results:The total effective rate of the case group was 93.06%,higher than 76.32%of the control group(P<0.05).Case group HBV DNA negative rate,negative rate of hepatitis B virus surface antigen(HBsAg),negative rate of hepatitis B virus e antigen(HBeAg)were significantly higher than the control group(76.39%vs 59.72%,55.56%vs 31.94%,51.39%vs 29.17%),the difference was statistically significant(P<0.05).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),hyaluronic acid(HA),laminin(LN),typeⅢprocollagen after treatment(PCⅢ),typeⅣcollagen(CⅣ),inner diameter of portal vein,inner diameter of splenic vein,spleen thickness,resistance index,urea nitrogen(BUN),creatinine(Cr),interleukin-6(IL-6),interleukin-8(IL-8),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),TLR-4,TGF-β1,APRI are lower than before treatment,albumin(ALB)and renal blood The flow rate was higher than before treatment;liver function indicators,liver fibrosis indicators,liver and spleen imaging indicators,renal hemodynamic indicators,serum inflammatory factors,TLR-4 in the case group The improvement of TGF-β1 and APRI.Conclusion:Fuzheng Huayu Capsules combined with nucleoside antiviral drugs have a clear clinical effect on patients with HBV infection and decompensated liver cirrhosis,significantly improve the clinical symptoms of patients,improve liver and kidney function,reduce inflammatory factor production,and can effectively inhibit HBV replication.Certain promotion value is worthy of further clinical research.

Synthesis of (2S,4S)-2-Substituted-3- (3-Sulfanylpropanoyl)-6- Oxohexahydropyrimidine-4-Carboxylic Acids as Potential Antihypertensive Drugs

Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.

Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection

Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.

Synergistic Effects of 18β-glycyrrhetinic Acid Combined with Antituberculosis Drugs against Mycobacterium tuberculosis

The in vitro antibacterial activities of 18β-glycyrrhetinic acid alone or combined with first-line antituberculosis drugs including isoniazid（INH）,rifampicin（RFP） and streptomycin（SM） against Mycobacterium tuberculosis were detected using MABA method.The minimum inhibitory concentrations（MICs） of18β-glycyrrhetinic acid against M.tuberculosis H37Rv（ATCC 27294） and M.bovis（ATCC 19210） were 50 and 100 μg/m L,respectively.The MICs of two clinical drug-susceptible isolates and six drug-resistant isolates were 25-50 and 100-200 μg/m L,respectively.As 18β-glycyrrhetinic acid combined with INH,RFP and SM,they exhibited synergistic effects against six drug-resistant isolates,and MICs decreased significantly：MIC of INH decreased by 2-32 folds（FICIs 0.125-0.375）;MIC of RFP decreased by 4-8 folds（FICIs 0.240-0.490）;MIC of SM decreased by 4-16 folds（FICIs 0.165-0.460）.Traditional medicine monomer had low cytotoxicity on normal cell BHK-21 and could restraint SMMC fission.The results showed that 18β-glycyrrhetinic acid combined with anti-TB drugs（INH,RFP and SM） had good antibacterial activity against M.tuberculosis.These findings indicated that 18β-glycyrrhetinic acid might serve as the potential therapeutic compound for future development of anti-TB drugs.

Trend Analysis of Combined Drugs Creation （for Example Acetylsalicylic Acid）

The pharmaceutical market of Ukraine in January 2015 was registered 71 drug based acetylsalicylic acid （ASA）, for which 52% combined. The most common combinations of ASA with acetaminophen and caffeine （45.9%）, magnesium hydroxide （18.9%）, bisoprolol （10.8%）, ascorbic acid （8.1%）, clopidogrel （5.4%）. Comparing markets combined drugs ASA of Ukraine, the Russian Federation, 28 EU countries, Norway, Switzerland, India, Syria, Australia and the USA identified the active pharmaceutical ingredients, combined with ASA in a single dosage form. The analysis of questionnaires 40 pharmacists pharmacies Temopil, Khmelnytsky and Kyiv regions of Ukraine noted that the biggest demand is mono-drugs ASA, Citramon, Askofen and Cardiomagnyl Methods of pharmacoeconomic studies proved efficient use Upsaryn UPSA with vitamin C tabl. spike, tuba in box number 20 BMS （France）, Citramon tablets number 6 PJSC ＂Monfarm＂ （Ukraine） and Cardiomagnyl tabl. film-coated shell 75 mg in bottle number 100 Nycomed Austria （Austria）. On the basis of six State Forms of drugs in Ukraine （2009-2014） was found that the combination of drugs based on ASA is recommended to use of ascorbic acid （Aspiryn C, Asprovit C, Upsarin UPSA with vitamin C）, dipyridamole （Agrenox）, magnesium hydroxide （Cardiomagnyl, Cardiomagnyl Forte）. Some of the standard combination of ASA （combination of paracetamol and caffeine） are not in form. For optimize State Form of drugs by improving health system in Ukraine can be useful pharmacoeconomic analysis of combination therapies with the current official system to note the combination of ASA with statins, esomeprazole, isosorbide.

Comparative Study of Solubility of Tranquilizers(Alternative Date Rape Drugs)in Stomach Acid

Date Rape Drugs are the members of tranquilizers and sedative class of drugs.These are the substances that make it easier for someone to rape or assault sexually.The person who is administrated by these drugs can cause sleepiness,slow breathing,slow heartbeat rate,trouble in muscle coordination,loss of consciousness.GHB(gamma-hydroxybutyric acid),Rohypnol(flunitrazepam),Ketamine are generally considered as date rape drugs.As Food and Drug Administration Department of Central Government of India considered this issue and placed these drugs under the schedule of Narcotic Drugs and Psychotropic Substances Act.Thereafter it is nearly impossible to get these drugs easily.But criminals have been searched new way through it.Normal tranquilizers and sedatives are also being used for committing such crimes.These drugs are also scheduled,but one can get them with prescription from a registered medical practitioner.So we carried out a comparative study of 3 tranquilizers from the benzodiazepine class that are Diazepam,Alprazolam,and Librium to check their dissolving rate in stomach acid.Estimation of action time of drug can help an investigator to identify the class of drug and time of drug injected(early phase).In our study,we found that the dissolving period of Diazepam and Alprazolam is more than conventional drugs.

Preparation and Drug-Release Property of Polycaprolactone (PCL)/Polyglycolic Acid (PGA) Composite Masterbatch with Drug of Tea Polyphenols (TPs)

In order to effectively control the drug-release rate of medical textiles,biodegradable polycaprolactone(PCL) and polyglycolic acid(PGA) were blended at various mass ratios to prepare composite masterbatches for medical textiles.The surface morphology and the chemical structure of the masterbatches were analyzed.The crystallization,mass losses,strengths and drug-release rates of the composite masterbatches at different PCL/PGA mass ratios were explored.The results show that the degradation rate of the PGA carrier is obvious higher than that of the PCL carrier,and PCL,PGA and the tea polyphenol(TP) drug just physically mix without chemical reaction.During the degradation,the strength of the composite masterbatches gradually decreases.In addition,the drug-release rates of composite masterbatches at different mass ratios are different,and the more the PGA in the composite masterbatches,the faster the drug release of the composite masterbatches.The drug-release rate of the composite masterbatches can be controlled by adjusting the contents of PCL and PGA.

Inhibitory Effect of 5-Adenylic Acid on Bitter Taste of Antipsychotic Drugs

The purpose of the present study was to examine the effect of adenylic acid (adenosine 5-monophosphate;AMP), a known nutritional enhancer, on inhibiting the bitterness of antipsychotic medicines administered to patients with mental illnesses, including children. First, we chose four antipsychotic medicines, amitriptyline hydrochloride (AMT), chlorpromazine hydrochloride (CPZ), haloperidol (HPD) and risperidone (RIS) and evaluated the inhibition of their bitterness by AMP through taste sensor measurements. AMP showed a significant bitterness inhibition effect on all drugs. Second, MarvinSketch analysis revealed the potential formation of electrostatic interactions between ionic forms (IV) of AMP and ionic (cationic) forms of each drug, which resulted in bitterness suppression. Third, chemical shift perturbations in 1H-NMR studies suggested an interaction between the phosphate group of AMP and amino group of AMT, CPZ, HPD and RIS. Last, conventional elution experiments of up to 1 min simulating oral cavity conditions were performed for 1 whole AMT tablet, half AMT tablet, crushed half AMT tablet, and crushed AMT tablet containing AMP powder/solution (1, 3 mM potency). The taste sensor output values of the crushed AMT tablet containing AMP powder/solution (1, 3 mM potency) were significantly lower than those of the crushed tablet.