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  • 27 November 2017 Volume 36 Issue 12
      

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  • Junzi CAO,Dezhi YANG,Li ZHANG,Guanhua DU,Yang LYU
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    Objective To evaluate the polymorphism of levonorgestrel by kinds of analysis technologies, and get the preponderant pharmaceutical polymorph by in vitro assessment including the stability and solubility. Methods Three polymorphs were obtained by quick solvent removal and precipitation methods. These polymorphs were characterized by X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), Raman spectroscopy and microscope. Furthermore, the stability was studied by X-ray powder diffraction analysis technology and using the curve of solubility to evaluate the dissolution rate of the three crystal forms. Results The levonorgestrel polymorphs α, β and γ were identified. The results of stability indicated that the levonorgestrel polymorphs α and β were metastable while the levonorgestrel polymorph γ was stable,and the dissolution rate of α, β, γ decrease in turn. Conclusion The levonorgestrel polymorph α is preponderant pharmaceutical polymorph. And the research on preponderant pharmaceutical polymorph of levonorgestrel provides scientific basic data for its clinical drug evaluation and establishing the quality standards.

  • Liming YUAN,Xianxian ZHOU,Mengjie YANG,Wanxin OUYANG,Shijie JIA,Xiangguan LIU,Haochu MAO,Xiaojun TAO,Huazhong YANG
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    Objective To investigate the effect of the Shaofu zhuyu decoction on the changes of the body writhing behavior,inflammatory reaction and COX-2 expression of the rats with the primary dysmenorrhea. Methods Fifty SD female rats were randomly divided into blank control group,model control group,high,middle and low dose of Shaofu zhuyu decoction groups,10 in each group.Dysmenorrhea rat model was established by treating with estradiol benzoate and oxytocin.Effect of Shaofu zhuyu decoction of different doses on writhing behavior,changes of endometritis cells and COX-2 expression in uterine smooth muscle of dysmenorrhea rats were observed. Results In the model control group,latency of the body writhing behavior was shortened and the total score was high,many inflammatory cells (especially for neutrophils) infiltrated in endometrium and uterine smooth muscle,immunohistochemistry showed that brown granules were found in the cytoplasm of smooth muscle cells of uterus,and COX-2 expression was positive in uterine smooth muscle cells.As compared with the model control group,writhing latency increased,total score decreased in both the high and middle dose of Shaofu zhuyu decoction groups,and infiltration of a small number of inflammatory cells was seen in the endometrium and smooth muscle (P<0.01);COX-2 expression was decreased (P<0.01) especially for the high dose of Shaofu zhuyu decoction group.As compared with the model control group,the latency of the low dose of Shaofu zhuyu decoction group was significantly increased,and the total score was decreased (P<0.01),but there was no significant difference in inflammatory cell infiltration and COX-2 expression (P>0.05). Conclusion A potential mechanism by which Shaofu zhuyu decotion treats primary dysmenorrhea may be related with alleviating pain,inhibiting inflammatory responses,and down-regulating expression of COX-2.

  • Xiaojin ZHAO,Lingyu LI,Li LI,Chunyin TANG,Hongzhi LI,Jieting LIU,Chunlei ZHANG,Yan WU,Xiaohuan YUAN
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    Objective To investigate the influence of curcumin and its analogue H8 on glucose and lipid metabolism disorder in db/db mice. Methods The type 2 diabetes mouse model (db/db mice) was intragastrically administrated with curcumin and analogue H8 for 8 weeks.The blood biochemical indexes were measured.The expression of PEPCK and G6Pase mRNA was detected by real-time PCR in liver tissues.The expression of PEPCK and G6Pase protein was detected by Western blotting. Results Curcumin analogue H8 reduced blood glucose and lipids in db/db mice (P<0.01) and improved liver function related enzymes significantly.The levels of PEPCK and G6Pase mRNA in db/db mice were significantly decreased (P<0.01) and the expression levels of PEPCK and G6Pase protein were significantly decreased (P<0.01). Conclusion Curcumin analogue H8 improves the glucose and lipid metabolism disorder in db/db mice,and it is related to inhibiting the expression of PEPCK and G6Pase gene and protein.

  • Jian LEI,Guangli TAO
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    Objective To study the protective effect of Xuemailing on pituitrin-induced myocardial rats. Methods The rats were divided into 7 groups(by means of random number table), 10 rats in each group, namely blank control group, model control group, Di'aoxinxuekang group and experimental groups (Xuemailing prepared fleece flower root high and low dose groups; Xuemailing raw radix polygoni multiflori high and low dose groups), each group was ig administrated once every day for 7 days, Blank control and model control groups were given the same volume of purified water. Effects of 7 groups on T wave and S-T segment were observed, LDH,CK,SOD,MDA activities in serum of rats were determined. Results High dose Xuemailing (prepared fleece flower root) significantly decreased the elevation of 10,30,45 s,1 min ST segment and 10,30,45 s T wave in the myocardial ischemia rat model.Low dose Xuemailing (prepared fleece flower root) significantly decreased the elevation of 10 s,1 min ST segment and 10 s T wave of the rat model.High dose Xuemailing (raw radix polygoni multiflori) significantly decreased the elevation of 10 s ST segment and 10,45 s T wave in the rat model.Xuemailing (prepared fleece flower root) and Xuemailing (raw radix polygoni multiflori) significantly decreased LDH,CK,MDA enzyme activities,and increased SOD enzyme activities of the myocardial ischemia rat model. Conclusion Xuemailing can protect the myocardial ischemia rats induced by pituitrin.

  • Shali WANG,Lin YANG,Yong LIU,Chaoran YAO,Shuang SONG,Yang LIU,Xiaohuan YUAN,Yan WU
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    Objective To evaluate the inhibitory effect of asiaticoside on bleomycin-induced skin cicatrization. Methods Thirty male C57BL/6 mice were randomly divided into three groups: negative control group,model control group,and asiaticoside group,ten in each group.In model control group and asiaticoside group,1 mg·mL-1 bleomycin was subcutaneously injected into the dorsal skin of mice every day;4 h later,1 mL 0.9% sodium chloride solution 1 mL asiaticoside (20 mg·mL-1) was injected into the lesion skin in the model control group and the asiaticoside group,respectively.In the negative control group,the same volume of 0.9% sodium chloride solution was subcutaneously injected into the dorsal skin of the mice at the two time points every day.After 21 days,skin specimens were harvested to observe the histomorphology and detect myofibroblast proliferation and expression of inflammatory factors. Results The skin scar was significantly attenuated in the asiaticoside group as compared with the model control group,and the dermal thickness measured exhibited a gradual decrease in asiaticoside group.The expression of α-antismooth muscle antisbidy and infiltration of inflammatory cells were significantly lower in the asiaticoside group than in the model control group. Conclusion Asiaticoside inhibits the development of skin scar of mice by regulating proliferation and differentiation of myofibroblasts and down-regulating inflammatory cells.

  • Chenghui HE,Honglin TIAN,Xiaolong KANG,Jing LIU,Jun LU
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    Objective To observe the effects of Capparis spinosa total alkaloid on vascular endothelial growth factor (VEGF),endothelin-1 (ET-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in systemic sclerosis (SSc) mouse model and explore the therapeutic mechanism of Capparis spinosa total alkaloid for the treatment of SSc. Methods A total of 90 BALB/c mice were randomly divided into blank control group,model control group,penicillamine (125 mg·kg-1) group and Capparis spinosa total alkaloid low (225 mg·kg-1),medium (450 mg·kg-1) and high (900 mg·kg-1) dose group.Except for the blank control group,SSc mouse model was established by daily subcutaneous injection of bleomycin in the back of the mice.After establishing model successfully,Capparis spinosa total alkaloid emulsifiable paste was externally applied with Capparis spinosa total alkaloid group,ground substance was externally applied to the mice in blank control group and model control groups,penicillamine was intragastrically administrated in the penicillamine group for 60 days,once daily.After the treatment,the content of VEGF in skin tissue and ET-1,sVCAM-1 in serum were measured by ELISA. Results The levels of VEGF and ET-1 were significantly decreased in Capparis spinosa total alkaloid high dose group as compared with model control group (P<0.05,P<0.01),but the content of sVCAM-1 wasn't influenced (P>0.05). Conclusion Capparis spinosa total alkaloid is effective in adjusting abnormal expression of VEGF and ET-1 in SSc mice.

  • Shuya SHE,Jinqi LI,Lu CHEN
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    Objective To observe the immunological mechanism of glycyrrhizic acid ointment on chronic eczema mouse model. Methods Mice were randomly divided into blank control group,model control group,base material group,dexamethasone acetate cream group,glycyrrhizic acid ointment high,medium and low dose groups.Except for the blank control group,chronic eczema mouse model was established by chronic repeated 2,4-nitrochlorobenzene stimulation.The contents of IL-4,IL-18,IFN-γ in serum and the T lymphocyte subpopulation in the peripheral blood were all determined after 14 days. Results Glycyrrhizic acid ointment in high,medium groups could significantly reduce the contents of interleukin (IL)-2,IL-5,IL-6,IL-18,interferon (IFN)-γ in serum,with significant differences as compared with the model control group (P<0.01 or P<0.05).The content of IL-4 in serum was significantly increased in the glycyrrhizic acid ointment high,medium groups as compared with the model control group (P<0.01 or P<0.05).Compared with model control group,CD4+T lymphocyte percentage and CD4+/CD8+T in peripheral blood were significantly increased,and CD8+T lymphocyte percentage decreased significantly (P<0.01 or P<0.05). Conclusion Glycyrrhizic acid ointment's effect of treating chronic eczema may be related to regulating the balance of Th1 and Th2 and correcting the immune disorders.

  • Sha LIAO,Lifeng FAN,Heng LIAO,Yujiao GAO
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    Objective To discuss the clinical therapeutic effect of Kangmin xiaoyan lotion combined with levocetirizine hydrochloride in the treatment of facial recurrent dermatitis. Methods Eighty cases of facial recurrent dermatitis were randomly divided into treatment group and control group,40 cases in each group.The treatment group was given Kangmin xiaoyan lotion with wet compression for 20 min in the morning and evening,and levocetirizine hydrochloride 10 mL orally once daily;the control group was only given levocetirizine hydrochloride orally once daily.One month later,the symptoms and signs of skin lesions and adverse reactions in each group were observed. Results One month after the treatment,the scores of symptoms and signs were significantly decreased in the two groups (P<0.05).After the treatment,the scores were significantly different between the two groups (P<0.05).Clinical efficacy of the treatment group and control group was 92.5% and 65.0%,with significant difference (P<0.05). Conclusion Kangmin xiaoyan lotion can be effective in the treatment of facial recurrent dermatitis,and it is worthy of clinical application.

  • Zhaoling CHEN,Qihuan LIU,Jingyi LIU,Xiaoduan JIANG,Ying XUE
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    Objective To explore and compare the clinical curative effect of tocilizumab and leflunomide in the treatment of rheumatoid arthritis and to evaluate the safety. Methods From March 2015 to March 2016,70 cases of rheumatoid arthritis treated in the department of rheumatism in this hospital were divided into treatment group and control group by using a random number table method,35 cases in each group.The patients in the observation group were intravenously treated with tocilizumab,at dosage of 8 mg·kg-1,once every four weeks.The control group was treated by oral administration of leflunomide tablets,at 50 mg·d-1 from the 1st to 3rd day,and at 20 mg·d-1 from the fourth day to the end of the treatment.The treatment period was 24 weeks in the two groups.Joint swelling,joint pain,morning stiffness,ESR,CRP,IL-6 and IL-8 were recorded and compared before and during the treatment.Total effective rate of treatment was compared between the two groups.Adverse drug reaction was recorded and the incidence of adverse drug reactions was compared. Results After the treatment,joint swelling,joint pain,morning stiffness,ESR,CRP,IL-6 and IL-8 were significantly lower in the treatment group than those in the control group (P<0.05).After the treatment,the total effective rate of the treatment was significantly higher than that of the control group (P<0.05).After the treatment,incidence of adverse reaction was significantly lower in the treatment group than that in the control group (P<0.05). Conclusion Tocilizumab and leflunomide has certain curative effect in the treatment of rheumatoid arthritis,but tocilizumab is more effective,with low incidence of adverse reaction and a high clinical value.

  • Shiwen DI,Can ZHOU,Sha LIAO,E CHEN
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    Objective To compare the influence of different processing methods on polysaccharide content in Morinda Officinalis. Methods Reflux extraction was performed with 80% ethanol.Ultraviolet spectrophotometery was used to determine the polysaccharide content after Phenol-sulferic acid method. Results Morinda officinalis was treated with different processing methods to remove moody core.The polysaccharide content in Morinda officinalis was the highest by cooking method (4.001±0.004)%,and the next was steaming method with salt (2.312±0.006)%,the sequence of the others was moistening method (2.163±0.010)%,steaming method after soaking (1.910±0.008)%,soaking method (1.731±0.008)% and steaming method (1.123±0.013)%. Conclusion The highest polysaccharide content is obtained in Morinda officinalis when processed by cooking method for removing woody core.

  • Shanchun WANG,Xiquan ZHANG,Yang LI,Hui LI
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    Objective To establish a method for simultaneous determination of petroleum ether (60-90 ℃),ethyl acetate,ethanol and pyridineas residual organic solvents in imatinib mesylate API. Methods Capillary gas chromatography was adopted.The determination was performed on DB-WAX capillary column with FID detector.The injector temperature was 180 ℃ and the temperature of FID was 200 ℃ by temperature programming with nitrogen serving as carrier gas at a flow rate of 5 mL·min-1.The injection volume was 1 μL.With N,N-dimethylformamide(DMF) serving as solvent,four kinds of organic solvent residues in the samples were calculated by external standard method. Results The four kinds of organic solvent were completely separated under the established chromatographic condition.A good linearity was obtained in the concentration ranges of them (r=0.999 8-0.999 9).The sampling precisions (RSDs) were less than 2.0%(n=5).The average recovery rates of ethyl acetate,ethanol and pyridine were 97%-101%and that of petroleum ether was 88.7%(RSD<2.0%,n=5).The limits of detection for them were 0.58,0.42,0.18 and 0.61 ng respectively (S/N=3:1).The limits of quantification for them were 1.8,2.1,0.5 and 2.5 ng,respectively (S/N=10:1). Conclusion The method is simple,sensitive,accurate and reliable.

  • Xuejia XIE,Jingyan RAN,Wenqing WANG
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    Objective To establish a HPLC method for the determination of related substances in lysine hydrochloride and zinc gluconate oral solution. Methods The HPLC separation was performed at 30 ℃ on an Inertsil Amide column (4.6 mm×250 mm,5 μm) by gradient elution with mobile phase A [phosphatesolution (2.72 g KH2PO4 and 0.46 goctane sulfonate,added with 1 000 mL)-acetonitrile (22:78)] and B [phosphate solution-acetonitrile (95:5)] at the flow rate of 1.0 mL·min-1.The clumn temperature was 30 ℃.The determination wavelength was 203 nm. Results The major peaks were well separated from adjacent related substances peaks and resolution were greater than 2.0.The theoretical plate number of major peaks and related substance peaks were greater than 3 000.Excipients and destruction test products did not interfere with the determination. Conclusion This method is practicable,specific and durable for the simultaneous determination of related substances in lysine hydrochloride and zinc gluconate oral solution.

  • Chengxin LI,Xueping WANG,Feng CUI,Haijun HAO
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    Objective To establish a rapid and accurate method for quantitative determination of erlotinib hydrochloride by proton nuclear magnetic resonance (1H-NMR). Methods Maleic acid was used as an internal standard,and DMSO-d6 was employed as solvent.The pulse width was 9.54 μs,the delay time was 20 s,the scanning frequency was 64 and the testing temperature was set as 300 ℃.Under this condition,the 1H-NMR data of the mixture of erlotinib hydrochloride and maleic acid were obtained.The content of erlotinib hydrochloride was calculated by comparing the response signal area of sample (As) and internal standard (Ar). Results Proton signal peaked at δ 8.84 and δ 8.47 for erlotinib hydrochloride and at δ6.26 for maleic acid served as quantitation peaks.The content of erlotinib hydrochloride was obtained by calculating the average of the test results of the two quantitative peaks.The concentration of erlotinib hydrochloride (2.88~19.08 mg·mL-1) and the peak area of quantification peaks showed a good linear correlation.The precision RSD was 0.36% (n=6),the repeatability RSD was 0.83% (n=6) and the sample recovery was 100.91% (n=6).The content of 3 batches of erlotinib hydrochloride was 92.26%,91.94% and 92.09%,the average was 92.10% and its RSD was 0.17%.The obtained results were generally consistent with those obtained from mass balance method. Conclusion This established method is simple to handle as compared to traditional methods,and the analysis results are accurate.1H-NMR provides a novel method for the determination of erlotinib hydrochloride and can be used for the quality control of erlotinib hydrochloride.

  • Liangliang LI,Xiaoqiang REN,Ziran XU,Shiyong XIN,Jianguo ZHANG
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    Objective To evaluate the efficacy and safety of combined therapy with 89Sr for treating skeletal-related events of prostate cancer. Methods Databases including PubMed,MEDLINE,EMBASE,the Cochrane library,CNKI,CBM and Wanfang were systematically searched since 89Sr was first reported in 1976 to September 2015 to include the randomized controlled trials (RCTs) of the combined therapy with 89Sr for skeletal-related events of prostate cancer.The statistical analysis was performed using Review Manager Version 5.2. Results A total of 18 RCTs involving 1 280 patients were analyzed.The results of meta-analysis indicated:there were statistically significant differences in the pain relief rate [OR=4.71,95%CI(3.34,6.62),P<0.000 1],decrement rate of bone metastasis [OR=3.63,95%CI(2.60,5.09),P<0.000 1] and improvement rate of life quality [OR=2.16,95%CI(1.16,4.02),P<0.05].Progression-free survival of patients in experimental group was significantly longer than that in control group [HR=0.84,95%CI(0.73,0.97),P=0.02].No significant difference was found in overall survival [HR=0.82,95%CI(0.65,1.02),P=0.07].There were no significant differences in the incidence of adverse events [OR=1.46,95%CI(0.98,2.17),P>0.05]. Conclusion Combined therapy with 89Sr has better efficacy and comparable safety profile compared with standard therapy.However,the quality and sample size of the included studies are limited,so more high-quality and large-sample RCTs are needed to verify the validity.

  • Jindong WU,jinchun QIU,Yong ZHANG
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    Objective To investigate the pharmacy practice of clinical pharmacists' attendance in the treatment of adverse reactions caused by drug interactions. Methods Analysis was conducted on the causes and treatment of hypertension in one pedinatric patient with aplastic anemia induced by combined use of cyclosporine and voriconazole. Results Cyclosporine A could lead to prolonged hypertension.Cyclosporine A dosage should be adjusted;antihypertensive drugs should be used in necessity.When choosing antihypertensive drugs,drug interaction with cyclosporine A should be considered. Conclusion Clinical pharmacists could manage adverse drug reactions by analyzing drug interactions,and offer suggestions for ADR patients.

  • Jing WU,Wei TONG,Hong CHEN,Xingfu HUANG,Wanhua YANG,Jie FANG
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    Objective To investigate the mode and effects of clinical pharmacists participating in clinical treatment and providing pharmaceutical care. Methods The clinical pharmacists participated in the treatment of the case of thymoma complicated with pulmonary infection in respiratory intensive care unit (RICU),associated with the myasthenia gravis (MG),pure red cell aplasia (PRCA) and lower extremity deep vein thrombolysis (LEDVT),through adjustment of drug regimen,observation of curative effect,monitoring blood drug concentration and adverse reaction and interaction monitoring,which could give full play to the professional expertise of pharmacy,and contribute to the clinical rational drug use. Results For patients with impaired immune function complicated with pulmonary infection,the opportunistic infections require special attention,during the initial anti-infective therapy.When the patient was unable to tolerate high doses of sulfamethoxazole and trimethoprim (SMZ-TMP),the clinical pharmacist recommended to use caspofungin for the combined treatment of pneumocystis pneumonia.When voriconazole and cyclosporine A (CsA) were used at the same time,the blood drug concentration of CsA would be increased,due to drug interactions probably.To solve the problem,clinical pharmacists recommended a temporary reduction in CsA dose. Conclusion Clinical pharmacists use pharmaceutical expertise to help optimize clinical treatment regimens,can improve the safety and effectiveness of drug treatment.

  • Xiaomei WANG,lin ZHAGN
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    ObjectiveTo analyze adverse reaction of voriconazole in Zhejiang province,and provide reference for safe and rational clinical use of it. Methods Eighty-four cases of voriconazole ADR reported from 2013 to 2015 were analyzed in terms of sex,age,mode of administration,time of ADR,combined drug use,organ or system involvement,outcome,etc. Results In the 84 cases of voriconazole ADR,the number of males was higher than that of females,aged 22 to 95 years old,and most cases were more than 60 years of age,accounting for 75.00%.Forty-six cases were caused by intravenous infusion,accounting for 54.76%,31 ADR cases were caused by oral administration,accounting for 36.90%,7 ADR cases were caused by intravenous infusion and oral administration,accounting for 8.33%.In 20 cases,ADR occurred immediately or on the administration day,accounting for 23.81%,and ADR in 36 cases occurred 2 to 10 days after the administration,accounting for 42.86%.The clinical manifestations of ADR were mainly digestive system injury,accounting for 31.58%,and the liver function abnormality was most common,mainly caused by oral administration;visual impairment was the second,accounting for 17.54%,mainly caused by the intravenous infusion;the proportion of nervous system injury was 16.67%,and the proportion of systemic reactions accounted for 11.40%. Conclusion During the period of clinical use,doctors,pharmacists,and nurses should strengthen the propaganda and education,recognition and prevention of voriconazole's ADR.The qualified hospitals may monitor the blood concentration and achieve individualized administration,to reduce the occurrence of ADR.

  • Xin CHEN,Ya ZHANG,Shiwei GONG
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    Improving the spatial agglomeration level of regional pharmaceutical industry is an important measure to promote the competitive ability of national industry.We used three evaluation indicators,Spatial Gini Coefficient,Location Concentration Ratio and Agglomeration Index,was to calculate the degree and speed of regional agglomeration of pharmaceutical industry from 2011 to Oct 2015.At present,China's pharmaceutical industry has formed spatial concentration,particularly concentrates in Shandong,Jiangsu and Guangdong.And the chemical pharmaceutical industry mainly concentrates in Shandong,Jiangsu,Guangdong and Beijing;Chinese traditional medicine industry concentrates in Shandong,Sichuan,Jilin and Jiangxi;biopharmaceutical industry concentrates in Shandong,Jiangsu,Henan.From the point of view of development speed,the agglomeration speeds of bio-pharmaceutical and traditional medicine industry are accelerating compared with the shrink of chemical pharmaceutical industry.Three provinces of the greatest growing speed of agglomeration for chemical,traditional medicine and bio-pharmaceutical industry are Jilin,Tibet and Jiangxi, respectively.Agglomeration growth of biopharmaceutical industry in western region is prominent.This paper suggests that the national government should play a leading role in the development of regional cluster for pharmaceutical industry.Some effective measures should be taken which include formulating the supporting policies of enterprise cluster,establishing the incentive system of drug innovation and optimizing the industrial portfolio in order to promote the formation of regional sustainable competitive advantage through agglomeration effect.