5种中药的酸性与药理作用的关系

某些中药具有一定的酸性,强度的大小与药理作用有着密切的关系。了解这种关系对中药的临床应用有着重要的参考价值。但这方面研究的报道较少。作者用pHS—3型精密酸度计测定了5种中药提取液的pH值,结果显示这5种中药均具有中等强度的酸性,属于酸性药。同时探讨了这5种酸性药在体内的药理作用。

“酸碱对药在方剂中的配伍化学研究”成果通过鉴定

由我院裴妙荣教授主持的国家自然科学基金项目“酸碱对药在方剂中的配伍化学研究”立项于2005年1月，项目组成员经过3年的不懈努力，于2007年12月完成研究。该项目首次提出酸性药、碱性药、酸碱两性药、中性药及酸碱对药的概念，潜藏着极有意义的研究空间，结合中医药理论，就此展开深人的探索，必将对中药药性理论和方剂配伍理论有实质性的充实和扩展；在中医药理论的指导下，从中药所含主要化学成分类群的角度出发，

Study on Kinetic Characteristics of Alliinase

[Objective] The kinetic characteristics of alliinase was studied to select the optimum reaction performance. [Method] Alliinase activity was measured to analysis the influence of temperature, pH, substrate concentration and metal iron. [Result] Alliinase was an enzyme with thermal instability. Its optimum reaction temperature was 29℃ and pH value was 6.1. The Vmax was 0. 439 IU/mg and Km was 0.483 mmol/L by using natural extract as substrate. Alliinase activity was activated when the K^＋ , Mg^2＋ , Na^＋ and Cd^2＋ existed and alliinase activity was inhibited when Cu^2＋ existed. [Condusion] Results showed that the kinetic characteristics of alliinase supply the academic foundation for development and application of garlic medical products.

Characteristics and Transdermal Drug Delivery of Triamcinolone-Acetonide-Acetate-Loaded Solid Lipid Nanoparticles Carbomer Gel

Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.

“广纸”使用耐磨抗蚀的钛风机

在酸法制浆工艺过程中,会遇到严重的设备腐蚀问题。特别是在酸性药液制备时,用来输送二氧化硫气体的风机,若是采用一般钢铁结构制成的话,它的叶轮和外壳,很快就会被磨损、腐蚀穿洞而无法使用。为此,广州造纸有限公司化浆车间曾先后在普通风机的叶轮表面上,挂上一层耐磨抗蚀的橡胶。

Protective Effect of Ascorbate-Lysine on Carbon Tetrachloride and Alcohol-Induced Liver Injury in Mice

As an essential amino acid, lysine boosts protein synthesis (Nestor et al1997). Yao et al demonstrated that, lysine also exerts protective effect against the isch-emiclesion of brain. Meanwhile, vitamin C is a natural antioxidant, which has undisputable protectiveaction against free radical damages. In order to ascertain whether their combination could affordbetter effect, we have investigated the prophylactic effect of the couplant ascorbate-lysine inliver injuries.

Development of a New Azithromycin Glutamate for Parenteral Preparation, the Toxicity in Sprague-Dawley Rats and Pharmacokinetics in Human Healthy Volunteers

Aim In order to improve the solubility of azithromycin, the objectives of the present study were to screen an appropriate salt for azithromycin by comparing acute hepatic and renal toxicities in animals, and study the pharmacokinetics of final chosen azithromycin salt. Methods Various salts of azithromycin, such as glutamate, citrate, hydrochloride, sulphate, dihydrogen phosphate, lactobionate, tartrate, and aspartate were given intravenously to Sprague Dawley rats at a dose of 10 mg once daily for 14 consecutive days via tail vein. The acute hepatic and renal indicators were measured before and after administration. A pharmacokinetic study was performed on 12 healthy human volunteers. The subjects were equally divided into two groups by a randomized crossover design. Azithromycin glutamate injection was administered by intravenous infusion or intramuscular injection at a single dose of 500 mg, respectively. Azithromycin concentrations in plasma were determined by microbial inhibition zone assay, and the pharmacokinetic parameters were calculated using a practical pharmacokinetic software 3P87 program. Results Azithromycin glutamate was least toxic to the liver and kidney of the rats, thus being selected as a final salt for parenteral preparation of azithromycin. Pharmacokinetic results showed that the area under the plasma concentration-time curves （AUC0-120h） were 21.47 ± 1.57 h·μg·mL^-1 for intravenous infusion, and 19.36 ± 2.44 h·μg·mL^-1 for intramuscular injection. The absolute bioavailability of intramuscular injection was 92.59%. Conclusion Azithromycin glutamate is suitable for the future clinical application, and its pharmacokinetics is characterized in human volunteers in the present study.

Theoretical Investigating Mechanisms of Drug-Resistance Generated by Mutation-Induced Changes in Influenza Viruses

Influenza A(A/H_(x)N_(y))is a significant public health concern due to its high infectiousness and mortality.Neuraminidase,which interacts with sialic acid(SIA)in host cells,has become an essential target since its highly conserved catalytic center structure,while resistance mutations have already generated.Here,a detailed investigation of the drug resistance mechanism caused by mutations was performed for subtype N9(A/H7N9).Molecular dynamics simulation and alanine-scanning-interaction-entropy method(ASIE)were used to explore the critical differences between N9 and Zanamivir(ZMR)before and after R294K mutation.The results showed that the mutation caused the hydrogen bond between Arg294 and ZMR to break,then the hydrogen bonding network was disrupted,leading to weakened binding ability and resistance.While in wild type(A/H7N9^(WT)),this hydrogen bond was initially stable.Meanwhile,N9 derived from A/H11N9 was obtained as an R292K mutation.Then the relative binding free energy of N9 with five inhibitors(SIA,DAN,ZMR,G28,and G39)was predicted,basically consistent with experimental values,indicating that the calculated results were reliable by ASIE.In addition,Arg292 and Tyr406 were hot spots in the A/H11N9^(WT)-drugs.However,Lys292 was not observed as a favorable contributing residue in A/H11N9^(R292K),which may promote resistance.In comparison,Tyr406 remained the hotspot feature when SIA,ZMR,and G28 binding to A/H11N9^(R292K).Combining the two groups,we speculate that the resistance was mainly caused by the disruption of the hydrogen bonding network and the transformation of hotspots.This study could guide novel drug delivery of drug-resistant mutations in the treatment of A/H_(x)N9.

Alverine citrate induced acute hepatitis

Alverine dtrate is a commonly used smooth muscle relaxant agent.A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent.A 34- year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening.Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment. Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case,several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity.

A novel phenol-bound pectic polysaccharide from Decalepis hamiltonii with multi-step ulcer preventive activity

AIM: To investigate H+, K+-ATPase inhibition, anti-H pylori , antioxidant, and the in vivo antiulcer potential of a pectic polysaccharide from Swallow root (Decalepis hamiltonii; SRPP). METHODS: SRPP, with known sugar composition [rhamnose: arabinose: xylose: galactose in the ratio of 16:50:2:32 (w/w), with 141 mg/g of uronic acid] was examined for anti-ulcer potency in vivo against swim/ ethanol stress-induction in animal models. Ulcer index, antioxidant/antioxidant enzymes, H+, K+-ATPase and gastric mucin levels were determined to assess the anti- ulcer potency. Anti-H pylori activity was also determined by viable colony count and electron microscopic studies. RESULTS: SRPP, containing phenolics at 0.12 g GAE/g, prevented stress-induced gastric ulcers in animal models by 80%-85%. Down regulation of gastric mucin 2-3 fold, antioxidant/antioxidant enzymes and upregulation of 3 fold of H+, K+-ATPase in ulcerous animals were normalized upon treatment with SRPP. Histopathological analysis revealed protection to the disrupted gastric mucosal layer and epithelial glands. SRPP also inhibited H+, K+-ATPase in vitro, at an IC50 of 77 μg/mL as opposed to that of 19.3 μg/mL of Lansoprazole and H pylori growth at Minimum Inhibitory Concentration (MIC) of 150 μg/mL. In addition, free radical scavenging (IC50-40 μg/mL) and reducing power (3200 U/g) activities were also observed. CONCLUSION: SRPP, with defined sugar composition and phenolics, exhibited multi-potent free radical scavenging, antioxidant, anti-H pylori, inhibition of H+, K+-ATPase and gastric mucosal protective activities. In addition, SRPP is non-toxic as opposed to other known anti-ulcer drugs, and therefore may be employed as a potential alternative for ulcer management.

Propylthiouracyl-induced severe liver toxicity:An indication for alanine aminotransferase monitoring?

Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.

Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model

To improve anti-inflammatory activity while reducing drug doses, we developed a nanoformulation carrying dexamethasone and butyrate.METHODSDexamethasone cholesteryl butyrate-solid lipid nanoparticles (DxCb-SLN) were obtained with the warm microemulsion method. The anti-inflammatory activity of this novel nanoformulation has been investigated in vitro (cell adhesion to human vascular endothelial cells and pro-inflammatory cytokine release by lipopolysaccharide-induced polymorphonuclear cells) and in vivo (disease activity index and cytokine plasma concentrations in a dextran sulfate sodium-induced mouse colitis) models. Each drug was also administered separately to compare its effects with those induced by their co-administration in SLN at the same concentrations.RESULTSDxCb-SLN at the lowest concentration tested (Dx 2.5 nmol/L and Cb 0.1 μmol/L) were able to exert a more than additive effect compared to the sum of the individual effects of each drug, inducing a significant in vitro inhibition of cell adhesion and a significant decrease of pro-inflammatory cytokine (IL-1β and TNF-α) in both in vitro and in vivo models. Notably, only the DxCb nanoformulation administration was able to achieve a significant cytokine decrease compared to the cytokine plasma concentration of the untreated mice with dextran sulfate sodium-induced colitis. Specifically, DxCb-SLN induced a IL-1β plasma concentration of 61.77% ± 3.19%, whereas Dx or Cb used separately induced a concentration of 90.0% ± 2.8% and 91.40% ± 7.5%, respectively; DxCb-SLN induced a TNF-α plasma concentration of 30.8% ± 8.9%, whereas Dx or Cb used separately induced ones of 99.5% ± 4.9% and 71.1% ± 10.9%, respectively.CONCLUSIONOur results indicate that the co-administration of dexamethasone and butyrate by nanoparticles may be beneficial for inflammatory bowel disease treatment.

Tannins from Canarium album with potent antioxidant activity

The contents of total phenolics and extractable condensed tannins in the leaves, twigs and stem bark of Canarium album were determined. The structural heterogeneity of condensed tannins from stem bark was characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF MS） and nuclear magnetic resonance （NMR） analyses The results show the predominance of signals representative of procyanidins and prodelphinidins. In addition, epicatechin and epigallocatechin polymers with galloylated procyanidin or prodelphinidin were also observed. The tannins were screened for their potential antioxidant activities using l,l-diphenyl-2-picrylhydrazyl （DPPH） and ferric reducing/antioxidant power （FRAP） model systems. Tannins extracted from leaves, twigs and stem bark all showed a very good DPPH radical scavenging activity and ferric reducing power.

Enantioselective assay of S(+)- and R(-)-propafenone in human urine by using RP-HPLC with pre-column chiral derivatization

The enantioselective assay for S(+)- and R(-)-propafenone (PPF) in human urine that developed in this work involves extraction of propafenone from human urine and using S(+)-propafenone as internal standard, chiral derivatization with 2,3,4,6-tetra-O-b-D-glucopranosyl isothiocyanate, and quantitation by an RP-HPLC system with UV detection (l=220 nm). A baseline separation of propafenone enantiomers was achieved on a 5-mm reverse phase ODS column, with a mixture of methanol:water:glacial acetic acid (25:12:0.02,v/v) as mobile phase. There was good linear relationship from 24.9 ng/ml to 1875.0 ng/ml for both of enantiomers. The regression equations of the standard curves based on CS-PPF (or CR-PPF ) versus ratio of AS-PPF/AS (or AR-PPF/AS ) were y=0.0032x-0.081, (r=0.999) for S-PPF and y=0.0033x+0.0039, (r=0.998) for R-PPF, respectively. The method抯 limit of detection was 12.5 ng/ml for both enantiomers, and the method抯 limit of quantitation was 28.20.52 ng/ml for S-PPF, 30.40.53 ng/ml for R-PPF (RSD<8%, n=5). The analytical method yielded average recovery of 98.9% and 100.4% for S-PPF and R-PPF, respectively. The relative standard deviation was no more than 6.11% and 6.22% for S-PPF and R-PPF, respectively. The method enabled study of metabolism of S(+)- and R(-)-propafenone in human urine. The results from 7 volunteers administered 150 mg racemic propafenone indicated that propafenone enantiomers undergo stereoselective metabolism and that in the human body, S(+)-propafenone is metabolized more extensively than R(-)- propafenone.

N-acetyl cysteine therapy in acute viral hepatitis

AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P＞0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

5-aminosalicylicacid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.

Study on Antithrombotic and Antiplatelet Activities of Low Molecular Weight Fucoidan from Laminaria japonica

The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.

SYNTHESIS AND DRUG RELEASE OF CROSSLINKING POLYPHOSPHATES

A new class of crosslinking polyphosphates were synthesized characterizedby IR 1HNMR, 31PNMR spectroscopy as well as elemental analysis. In vitrodegradation of the polyphosphates obtained and the release of antineoplastic drugMethotrexate (MTX) and contraceptive Levonorgestrel (LNG ) by nsing thesepolymers as matrix were studied. Zero order release rate was rkserved in the case ofLNG release.

Flotation performances of polymorphic pyrrhotite

The floatability of different crystalline structures of pyrrhotite(monoclinic and hexagonal) was studied.It is shown that the floatability of monoclinic and hexagonal has obvious difference,and that the flotation recovery of monoclinic pyrrhotite is larger than that of hexagonal pyrrhotite using different collectors.When butyl dithiophosphate is used as the collector,the recovery is larger than that by sodium butyl xanthate and sodium diethyl dithiocarbamate.At the pH values ranging from 6 to 9,monoclinic pyrrhotite can be floated well,and the flotation recovery is higher than 90%.Monoclinic and hexagonal pyrrhotites are more easily activated by Cu2+ in acidic conditions than in alkaline conditions.But Cu2+ cannot activate hexagonal pyrrhotite using sodium diethyldithiocarbamate as the collector.By the measurement of contact angle,it is indicated that monoclinic and hexagonal pyrrhotites float well and are easily activated by Cu2+ when dithiophosphate is used as the collector.Using sodium diethyl dithiocarbamate as a collector,the relationship between potential and pH range for pyrrhotite flotation is established.At pH 5,the optimal potential range for flotation of monoclinic pyrrhotite is about 125-580 mV(vs SHE),with the maximum flotation occurring at about 350 mV(vs SHE);the optimal potential range for flotation of hexagonal pyrrhotite is 200?580 mV(vs SHE),with the maximum flotation occurring at about 300 mV(vs SHE).

Study on Biocompatibility of Cross-linked Hyaluronic Acid Derivatives

Objective:The cross-linked production,which was prepared by HA and cross-linking agent STMP,EDC,GP through cross-linking reaction,might be used in drug delivery system(DDS).To ensure the security of clinical application,the excellent properties such as none cell toxicity,nonirritant,none general toxicity,none immunological rejection are necessary.Methods:In accordance with the request of GB/T 16886.1 on security evaluation of medical biomaterials,cell toxicity test,hemolysis test,intracutaneous stimulation test,acute toxicity test,and hypersensitive test were required.Results:Cell toxicity of HA-STMP,HA-EDC,HA-GP were all less than 1.All hypersensitive tests were eligible.But HA-EDC,HA-GP produced different degrees of slight thrill,slight toxicity,hemolysis rate,which were larger than the standard value.Conclusion:HA-STMP possesses favourable biocompatibility,which is a kind of ideal biomaterials and drug carriers.