Repurposing of US-FDA-approved drugs as negative modulators of ubiquitin specific protease-7 (USP7).

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of USP7 with dissociation constant (Kd) values in the range of 0.6-1.49 mM. These 11 compounds could thermally destabilize the USP7 enzyme by decreasing its melting temperature up to 9 °C. Molecular docking and simulation studies provided structural insights into the ligand-protein complexes, suggesting that these compounds bind to the putative substrate binding pocket of USP7, and interact with its catalytically important residues. Among the identified 11 hits, compound 6 (oxybutynin), 7 (ketotifen), 10 (pantoprazole sodium), and 11 (escitalopram) also showed anti-cancer activity with an effect on the expression of proto-oncogenes and tumor-suppressor gene at mRNA level in HCT116 cells. The compounds identified in this study can serve as potential leads for further studies.

Introducing of Li2FeMn3O8 /C-C3N4 /IL nanocomposite for electrochemical determination of pantoprazole sodium in real samples.

A new electrochemical sensor based on Li2FeMn3O8/C-C3N4 (LFMO/CCN)/1-ethyl-3-methylimidazolium chloride modified carbon paste electrode (CPE) has been constructed to measure pantoprazole sodium (PNZS). The electrochemical impedance spectroscopy (EIS) method was employed to evaluate the electrode charge-transfer resistances. Moreover, the differential pulse voltammetry method was used to detect PNZS in phosphate buffer solution (PBS) at pH 7.0. The detection limit of 80.0 × 10-9 M and 10.9 × 10-7 M was obtained under optimal conditions in the linear concentration range of PNZS 0.09-100 µM and 100-900 µM. Chronoampermetry technique was utilized to determine the diffusion coefficient (D) of PNZS on the modified electrode surface. The CCN/LFMO/IL/CPE was successfully used to determine PNZS in various drug formulations such as tablets and vials. Finally, simultaneous determination of PNZS and acetaminophen was accomplished with no interference based on the proposed sensor.

Prospects to the formation and control of potential dimer impurity E of pantoprazole sodium sesquihydrate.

Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP) specify six impurities, viz.; impurities A, B, C, D, E and F, respectively for its active pharmaceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature; however, there is no report related to impurity E. The prospects to the formation and controlling of impurity E up to ≤0.03% in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.

Prospects to the formation and control of potential dimer impurity E of pantoprazole sodium sesquihydrate / 药物分析学报

Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmaco-poeia (USP) specify six impurities, viz.; impurities A, B, C, D, E and F, respectively for its active phar-maceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature; however, there is no report related to impurity E. The prospects to the for-mation and controlling of impurity E up to ≤0.03％ in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.

Development of a dual extrusion printing technique for an acid- and thermo-labile drug.

Over the last years fused deposition modeling has been increasingly considered as a game-changing technique for the preparation of individualized pharmaceutical products. Until now investigations have mainly focused on dosage forms loaded with very stable drugs or model substances. Going beyond this early stage of research, developers will also have to deal with more challenging active substances. In this work different printing designs for tablets containing the acid- and thermo-labile drug pantoprazole sodium were tested. Initial dual extrusion printing of a cellulose acetate phthalate coat and a tablet core of polyethylene glycol 6000 with 10% (m/m) pantoprazole sodium resulted in thermal degradation of pantoprazole at cellulose acetate phthalate printing temperatures of 141 °C. Therefore, different tablet designs were developed. The sectioning of the design of the tablet coat in a gastro-resistant cellulose acetate phthalate bottom part and an upper nearly insoluble polycaprolactone part printed at only 58 °C was suitable to prevent visible signs of thermal degradation. Dissolution testing indicated also no drug loss during dual extrusion printing. However, printed enteric tablets with shell thicknesses of 0.4 to 0.5 mm were not completely gastro-resistant. Drug release at intestinal pH values was delayed compared to uncoated cores. In conclusion, 3D-printing of gastro-resistant tablets containing thermo- and acid-labile drugs seems in principle possible. However, it remains an unsolved challenge to meet United States Pharmacopeia requirements.

Immediate Release 3D-Printed Tablets Produced Via Fused Deposition Modeling of a Thermo-Sensitive Drug.

PURPOSE: Dissolution speeds of tablets printed via Fused Deposition Modeling (FDM) so far are significantly lower compared to powder or granule pressed immediate release tablets. The aim of this work was to print an actual immediate release tablet by choosing suitable polymers and printing designs, also taking into account lower processing temperatures (below 100°C) owing to the used model drug pantoprazole sodium. METHODS: Five different pharmaceutical grade polymers polyvinylpyrrolidone (PVP K12), polyethylene glycol 6000 (PEG 6000), Kollidon® VA64, polyethylene glycol 20,000 (PEG 20,000) and poloxamer 407 were successfully hot-melt-extruded to drug loaded filaments and printed to tablets at the required low temperatures. RESULTS: Tablets with the polymers PEG 6000 and PVP K12 and with a proportion of 10% pantoprazole sodium (w/w) demonstrated a fast drug release that was completed within 29 min or 10 min, respectively. By reducing the infill rate of PVP tablets to 50% and thereby increase the tablet porosity it was even possible to reduce the mean time for total drug release to only 3 min. CONCLUSIONS: The knowledge acquired through this work might be very beneficial for future FDM applications in the field of immediate release tablets especially with respect to thermo-sensitive drugs.

Safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects.

PURPOSE: The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects. METHODS: The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(-)-PPZ, 40 mg of single and multiple intravenous administration of S-(-)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(-)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(-)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination. RESULTS: All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(-)-PPZ were dose proportional over the range of 20-80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(-)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(-)-PPZ than 40 mg PPZ; however, the differences were not statistically significant. CONCLUSIONS: Twice daily of 40 mg S-(-)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(-)-PPZ, while a few subjects showed faster metabolic rate of S-(-)-PPZ in vivo.

Development of a novel and cost-effective redox sensor for voltammetric determination of pantoprazole sodium during pharmacokinetic studies.

A pencil graphite electrode modified with poly (bromocresol green (BCG)) was prepared by electro-polymerization process for the determination of pantoprazole sodium. The surface morphology and structure of poly (BCG) film were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The determination of pantoprazole sodium in Britton-Robinson buffer (pH 7.0) was carried out by square wave adsorptive stripping voltammetric technique. Under optimum conditions, the linear response of the peak with concentration of the cited drug was in the range of 6.6-360 × 10-8 M with limit of detection of 2.2 × 10-8 M. Moreover, the poly (BCG)-modified electrode has been successfully applied to determine pantoprazole sodium in tablets, vials and during pharmacokinetic studies.

Simultaneous voltammetric analysis of anti-ulcer and D2-antagonist agents in binary mixture using redox sensor and their determination in human serum.

Pencil graphite electrode was successfully modified with a thin film of poly (eriochrome black T) and applied for the sensitive and selective voltammetric simultaneous determination of pantoprazole sodium and domperidone in a binary mixture. The preparation and basic electrochemical behavior of poly (eriochrome black T) film on the Pencil graphite electrode were investigated. The modified electrode has exhibited very high electro-catalytic activity towards the cited mixture. The anodic peaks of the both species were well defined with enhanced oxidation peak currents. Under the optimum conditions, the linearity ranges were 0.4-55×10-7M and 0.1-34×10-7M for pantoprazole sodium and domperidone, respectively with detection limits of 0.12×10-7M and 0.04×10-7M for pantoprazole sodium and domperidone, respectively. The proposed sensor has been successfully applied in the analysis of pantoprazole sodium and domperidone in synthetic binary mixtures and human serum.

The efficacy and safety of Danhong injection combined with pantoprazole sodium on patients with acute exacerbation of respiratory failure / 中国生化药物杂志

Objective To investigate the clinical efficacy and safety of Danhong injection combined with pantoprazole sodium on patients with acute exacerbation of respiratory failure. Methods 104 patients with acute exacerbation of respiratory failure were treated in our hospital from January 2016 to January 2017. They were selected and equally divided into two groups with the method of random number table. The two groups were given the same basic treatment, and the control group was treated with pantoprazole sodium on this basis. The treatment group was treated with Danhong injection on the basis of the control group. The clinical efficacy and adverse reactions of two groups were recorded. Results After 15 days of the treatment, the total effective rate of the treatment group was 94.2%, which was significantly higher than that of the control group 71.2%(P<0.05). There was no significant difference in the incidence of adverse reactions between the control group and the treatment group. Conclusion Danhong injection combined with pantoprazole sodium is effective and safe in the treatment of acute exacerbations of respiratory failure, which is worthy of clinical practice and popularization.

The efficacy and safety of Danhong injection combined with pantoprazole sodium on patients with acute exacerbation of respiratory failure / 中国生化药物杂志

Objective To investigate the clinical efficacy and safety of Danhong injection combined with pantoprazole sodium on patients with acute exacerbation of respiratory failure. Methods 104 patients with acute exacerbation of respiratory failure were treated in our hospital from January 2016 to January 2017. They were selected and equally divided into two groups with the method of random number table. The two groups were given the same basic treatment, and the control group was treated with pantoprazole sodium on this basis. The treatment group was treated with Danhong injection on the basis of the control group. The clinical efficacy and adverse reactions of two groups were recorded. Results After 15 days of the treatment, the total effective rate of the treatment group was 94.2%, which was significantly higher than that of the control group 71.2%(P<0.05). There was no significant difference in the incidence of adverse reactions between the control group and the treatment group. Conclusion Danhong injection combined with pantoprazole sodium is effective and safe in the treatment of acute exacerbations of respiratory failure, which is worthy of clinical practice and popularization.

Determination of Pantoprazole Sodium Bioadhesive Tablets by HPLC / 中国药师

Objective:To establish a method to determine the contents of pantoprazole sodium bioadhesive tablets. Methods:An HPLC method was adopted. The determination was performed on a HYPERSIL ODS-2 (150 mm × 4. 6 mm, 5μm) column with mobile phase consisting of 0. 01 mol·L-1 dipotassium phosphate solution –methanol (60 ∶40) at the flow rate of 1. 0 ml·min-1 . The de-tection wavelength was set at 289 nm, the column temperature was maintained at 30 ℃ and the sample size was 20 μl. Results:The linear range of pantoprazole sodium was 1. 28-20. 60μg·ml-1,(r=0. 999 8) . The average recovery was 99. 52%(RSD=1. 43%, n=9). Conclusion:The method is simple, accurate and reliable, and can be used for determining the content of pantoprazole sodium bioadhesive tablets.

Psychological intervention method and effect analysis of pantoprazole sodium in the treatment of gastric ulcer / 中国生化药物杂志

Objective To explore the effect of psychological intervention with pantoprazole sodium in treatment of gastric ulcer. Methods A total of 80 patients with gastric ulcer from March 2015 to January 2017 were randomly divided into two groups, control group and observation group; Two groups were treated with pantoprazole sodium, the control group received conventional care, while the observation group was given psychological care.The rehabilitation of the two groups was observed and compared . Results The effective rate of observation group was 92.5％, significantly higher than that of the control group(77.5％); The satisfaction rate of the observation group was 97.5％, significantly higher than that of the control group 72.5％; the differences between the two groups were statistically significant.Conclusion The implementation of psychological nursing of pantoprazole in treatment of gastric ulcer in the process, can consolidate the curative effect to be fully reflected, help patients recover in time, and improve patient care for acceptance,it is worthy of reference.

Determination of Related Substances in Pantoprazole Sodium for Injection by HPLC / 中国药房

OBJECTIVE:To establish a method for the determination of related substances in Pantoprazole sodium for injec-tions. METHODS:HPLC method was adopted. The determination was performed on Kromasil Hypersil ODS column with mobile phases consisting of 0.01 mol/L potassium dihydrogen phosphate buffer solution(pH adjusted to 7.0)-acetonitrile(gradient elution) at a flow rate of 1.0 mL/min. The detection wavelength was set at 290 nm,and the column temperature was 40 ℃,and injection volume was 20 μL. RESULTS:The linear ranges of impurity A,impurity B,impurity C+E,and impurity D were 0.4168-1.0420μg/mL(r=0.9998),0.1950-0.4875 μg/mL(r=0.9999),0.3890-0.9725 μg/mL(r=0.9998),0.1986-0.4965 μg/mL(r=0.9998), respectively. The limits of quantitation were 0.834,0.780,1.556,0.794 ng/mL;the limits of detection were 0.417,0.390,0.778, 0.397 ng/mL,respectively. RSD of precision test was lower than 1.0%;in repetitive test,RSD for total peak area of impurity was lower than 1.0% ;the recoveries were 98.81% -102.49%(RSD=1.18% ,n=9),95.31% -98.44%(RSD=0.91% ,n=9), 96.88%-98.44%(RSD=0.52%,n=9)and 97.87%-101.28%(RSD=1.05%,n=9). CONCLUSIONS:The method is convenient, accurate and suitable for the determination of related substance in Pantoprazole sodium for injection.

Determination of (S)-Pantoprazole Sodium in Dog Plasma by LC-MS/MS and Its Toxicokinetic Study / 中国药学杂志

OBJECTIVE: To establish an LC-MS/MS method to determine (S)-pantoprazole sodium in dog plasma and investigate its toxicokinetics. METHODS: After protein precipitation with acetonitrile, the analyte and internal standard were separated on CHIRALCEL OJ-RH column (4.6 mm ×150 mm, 5 μm) with acetonitrile-water (28∶72) as mobile phase eluted at a flow rate of 0.6 mL·min-1. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The MRM transitions of m/z 384.0/199.8 and m/z 180.0/110.0 were used to quantify (S)-pantoprazole sodium and phenacetin, respectively. Beagle dogs were intravenously given (S)-pantoprazole sodium for 4 weeks at low, medium, and high dosages (10, 20, 40 mg·kg-1·d-1). RESULTS: The calibration curve was linear over the concentration range of 50-30 000 ng·mL-1. The RSDs were less than 15%, and the accuracy was in the range of 85%-115%. The AUC0-4 h and ρmax of (S)-pantoprazole sodium were proportional to the dosages. CONCLUSION: The established method can be applied to the determination of (S)-pantoprazole sodium in plasma of dogs and is suitable for the toxicokinetic study.

A novel model for NSAID induced gastroenteropathy in rats.

INTRODUCTION: Progress in management of Nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to develop a rat model for NSAID-induced gastroenteropathy and also to simulate the common clinical scenario of co-administration of NSAID and proton pump inhibitor (PPI) to explore if PPI contribute to exacerbation of NSAID-enteropathy. METHODS: Rats were treated twice daily with pantoprazole sodium (PTZ; 10mg/kg peroral) or vehicle for a total of 10days. In some experiments, Diclofenac sodium (DCF; 9mg/kg) or vehicle was administered orally twice daily for the final 5days of PTZ/vehicle administration. After the last dose on 9th day, rats in all the groups were fasted but water was provided ad libitum. 12h after the last dose on 10th day, rats in all the groups were euthanized and their gastrointestinal tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and gastrointestinal luminal pH alterations. Changes in haemoglobin, haematocrit and serum levels of albumin, total protein, ALT and bilirubin were calculated. RESULTS: The macroscopic and histological evidence suggested that administration of DCF resulted in significant gastroenteropathic damage and co-administration of PTZ resulted in significant exacerbation of NSAID enteropathy, while attenuation of NSAID induced gastropathy was observed. Our results were further supported by the significant decrease in haemoglobin and haematocrit levels and serum levels of albumin and total proteins, an increase in oxidative stress and intestinal permeability with the use of DCF either alone or in combination with PTZ. CONCLUSIONS: This model was developed to simulate the human clinical situation during NSAID therapy and indeed the present DCF regimen caused both gastric and small bowel alterations, such as multiple erosive lesions, together with a decrease in haemoglobin, haematocrit, serum albumin, serum total protein levels and IP alteration, known to occur in patients receiving NSAIDs. Additionally, this paper provides yet another evidence for PPI induced exacerbation of NSAID enteropathy.

Pantoprazole sodium inhibits epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells and underlying mechanism / 中国病理生理杂志

[ ABSTRACT] AIM:To explore the inhibitory effects of pantoprazole sodium on epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells and the underlying mechanism .METHODS: Using MTT method, wound healing assay , Transwell experiment , Western blot , the differences of morphology , invasion ability , migration ability , drug sensitivity and protein expression between A 549/DDP cells and A549 cells were determined .The effect of pantoprazole so-dium on morphology , invasion ability , migration ability , drug sensitivity and protein expression in A 549/DDP cells were al-so observed.RESULTS: Compared with A549 cells, A549/DDP cells had higher invasion and migration abilities , and lower drug sensitivity , exhibited mesenchymal phenotype and activated c-Met/AKT/mTOR pathway .Pantoprazole sodium inhibited the abilities of invasion and migration , and reversed the mesenchymal phenotype , drug resistance and the c-Met/AKT/mTOR pathway activation in A549/DDP cells.Treatment with c-Met inhibitor SU11274, PI3K inhibitor LY294002 and mTOR inhibitor rapamycin had the same effects on A 549/DDP cells as that of pantoprazole sodium .CONCLUSION:Pantoprazole sodium inhibits invasion , migration, epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells by down-regulating c-Met/AKT/mTOR pathways .

Novel potentiometric application for the determination of pantoprazole sodium and itopride hydrochloride in their pure and combined dosage form.

Three sensitive and selective polyvinyl chloride (PVC) matrix membrane electrodes were developed and investigated. Sensor I was developed using tetraheptylammonium bromide (THB) as an anion exchanger with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer for the determination of the anionic drug pantoprazole sodium sesquihydrate (PAN). To determine the cationic drug itopride hydrochloride (ITH), two electrodes (sensors II and III) were developed using potassium tetrakis(4-chlorophenyl) borate (KTCPB) as a cation exchanger with dioctyl phthalate (DOP) as a plasticizer. Selective molecular recognition components, 2-hydroxypropyl-ß-cyclodextrin (2-HP ßCD) and 4-tert-butylcalix[8]arene (tBC8), were used as ionophores to improve the selectivity of sensors II and III, respectively. The proposed sensors had a linear dynamic range of 1×10(-5) to 1×10(-2) mol L(-1) with Nernstian slopes of -54.83±0.451, 56.90±0.300, and 51.03±1.909 mV/decade for sensors I, II and III, respectively. The Nernstian slopes were also estimated over the pH ranges of 11-13, 3.5-8 and 4-7 for the three sensors, respectively. The proposed sensors displayed useful analytical characteristics for the determination of PAN and ITH in bulk powder, in laboratory prepared mixtures and in combined dosage forms with clear discrimination from several ions, sugars and some common drug excipients. The method was validated according to ICH guidelines. Statistical comparison between the results from the proposed method and the results from the reference methods showed no significant difference regarding accuracy and precision.

Protective effects of left-handed pantoprazole sodium on the rat model of gastric ulcer generated by pyloric ligation / 中国比较医学杂志

Objective The aim of this study was to investigate the effect of left-handed pantoprazole sodium on rat models of gastric ulcer generated by pyloric ligation .Methods The rat models induced by pylorus ligation were treated with a single intravenous injection of left-handed pantoprazole sodium .The gastric ulcer inhibition rate , volume of gastric juice, activity of pepsin, and level of serum gastrin were determined and gastric mucosa tissue was examined by pathology . Results The gastric ulcer index , volume of gastric juice , activity of pepsin and level of serum gastrin in the rats pretreated with left-handed pantoprazole sodium (0.9, 1.8, 3.6 mg/kg, i.v.) were significantly lower than those in the model group .The lesions of gastric mucosa were also improved in the pantoprazole-treated groups .Conclusions Left-handed pantoprazole sodium has remarkable protective effects on the gastric mucosa in rat models of gastric ulcer induced by pyloric ligation.

Clinical Observation of Somatostatin Combined with Pantoprazole Sodium in the Treatment of Severe Acute Pancreatitis / 中国药房

OBJECTIVE:To stndy the clinical efficacy and safety of somatostatin combined with pantoprazole sodium in the treatment of severe acute pancreatitis(SAP). METHODS:By retrospective analysis,98 patients with SAP were divided into control group and observation group by the different treatment. All patients were treated by routine treatment of SAP. Based on it,patients in control group were given Pantoprazole sodium for injection 40 mg adding into 0.9% sodium chloride injection 100 ml,iv,twice a day;patients in observation group were given Somatostatin for injection 3 mg adding into 0.9% sodium chloride injection 100 ml based on the treatment of control group,by micro intravenous continuous intravenous infusion,0.25 mg/h,twice a day.Both cours-es were 7 d. The clinical data was observed,including clinical efficacy,improvement time of signs and symptoms(remission time of stomachache,recovery time of gastrointestinal function,withdrawal time of ventilator) and tumor necrosis factor-α(TNF-α), high-sensitivity C-reactive protein (hs-CRP),interleukin-8 (IL-8) levels and the incidence of adverse reactions before and after treatment. RESULTS:The total effective rate in observation group was significantly higher than control group,and the improve-ment time of signs and symptoms was significantly shorter than control group,with significant differences(P<0.05). After treat-ment,the inflammatory cytokine levels in 2 groups were significantly lower than before,and observation group was lower than con-trol group,with significant differences(P<0.05). The incidence of adverse reactions in observation group was significantly lower than control group,with significant difference(P<0.05). CONCLUSIONS:Based on the routine treatment,somatostatin combined with pantoprazole sodium has better efficacy than only pantoprazole sodium,with better safety.