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Objective To prepare silymarin phospholipids complex(SM-PC) and investigate its physicochemical properties. Methods On the basis of single-factor tests, the drug-lipid ratio, drug concentration and reaction temperature were selected as the factors of the central composite design and response surface methodology in the preparation of SM-PC by solvent volatilization, and the best process was optimized with the compound rate as the index. And its in vitro dissolution was measured. Results The optimum preparation technology of SM-PC was as follows: acetone was used as compound solvent, the concentration of SM was 8.0 mg/ml, the mass ratio of SM to phospholipid was 1∶1.8, the reaction temperature was 56 ℃ and the recombination rate was(95.15±1.55)% with deviation of less than 3%. The in vitro dissolution test showed that the dissolution of SM-PC was close to 90% in 60 min. The dissolution behavior of main component of silybin was similar to that of silymarin capsules(Legalon ®), which was higher than SM-API. Conclusion SM-PC was successfully prepared by central composite design response surface method, which significantly improved the dissolution and laid a foundation for the study of subsequent preparations.
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Objective To investigate the quality and safety of liquid bandage and establish a reliable quality control method. Methods The quality of liquid bandage was evaluated by appearance, film forming time, viscosity, comfort, waterproof and air permeability. The content was determined by HPLC. The safety of liquid bandage was investigated with skin irritation test and allergy test. Results The self-made liquid bandage was uniform and delicate, with good ductility, fast film formation, good mechanical strength, waterproof and air permeability. The content of active pharmaceutical ingredients in the film met the requirements. It had no obvious irritation to the skin and no allergic reaction. Conclusion The established quality control method was reliable. The liquid bandage had good safety profile.
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Objective To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits. Methods The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study. Results Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.
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Objective To prepare a sustained-release membrane with longer adhesion time and dissolution time, and compare it with the commercially available oral ulcer membrane. Method Adhesion strength, adhesion time, swelling coefficient, dissolution time, etc. were used as the inspection indicators, and a combination of single factor inspection and analytic hierarchy process were used to screen the membrane -forming materials. The dispersion method of clotrimazole, ornidazole and borneol were investigated to prevent the drug from seed out. The method of combining orthogonal experiment and analytic hierarchy process were used to optimize the dosage of CMC-Na, PVA-1788 and glycerin; and the commercial products were compared. Results Through single-factor investigation and orthogonal experiment, the optimal ratio of excipients was selected as CMC-Na∶PVA-1788∶glycerol (3∶1∶0.08). The water-insoluble component clotrimazole, ornidazole and borneol were treated by precipitation in liquid with good effect. The best method was used to prepare the membrane. The adhesion strength was 102 g. The adhesion time was 55 min. The swelling coefficient was 1 939.52. The average dissolution time was 110 min. The appearance was white and the surface was free of bubbles, soft and elastic. The membrane forming time at 60 ℃ was 300 min and the demolding effect was better which could be completely peeled off with moderate thickness. Conclusion The oral ulcer membrane developed in this method has good appearance, comfortable use, strong adhesion, long adhesion time and dissolution time, and could stay on the ulcer surface for a long time to form physical isolation, and slowly release the drug during the dissolution process, which could play the role of long-term pain relief, antibacterial, anti-inflammatory and promote healing effects on oral ulcers.
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Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets(SM-PC MPOP). Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon(30 mg/kg). The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:(3.2±0.4)and(0.9±0.1)h, Cmax:(0.298 6±0.068 9)and(0.629 9±0.076 5)μg/ml, AUC0→24:(2.996 8±0.583 3)and(2.268 9±0.432 8)h·μg /ml. The relative bioavailability of SM-PC MPOP was(162.21 ± 30.82)%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine(r = 0.839 0).
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The clinical and imaging data of 99 patients with Graves′ disease, 78 patients with thyroiditis and 28 patients with other diseases (resolving thyroiditis, non thyroid disease and simple goiter) who underwent thyroid scintigraphy in Beijing Shijingshan Hospital from January 2016 to March 2022 were retrospectively reviewed. The UR value of thyroid scintigraphy was calculated and ROC curve was used to assess the UR value in diagnosis of Graves′ disease. The UR value of patients with Graves′ hyperthyroidism was significantly higher than that of patients with thyroiditis and other diseases ( H=163.62, P<0.05). UR>4.84 was taken as optimal cutoff value to diagnose Graves′ hyperthyroidism, with the sensitivity and specificity of 95.0% and 98.1%, respectively.
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Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.
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Liquid band-aid is a new type of wound dressing that has emerged in recent years. Compared with traditional band-aid, it has the advantages of convenient use, natural shedding, good waterproof and breathable effect, and easy fitting for irregular wounds. It has brought a great convenience to the wound treatment in our daily life. This paper reviews the current research status of liquid band-aids at home and abroad and summarizes the research progress on film forming materials for liquid band-aids with the purpose to provide references for the further development and improvement of liquid band-aids.
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Objective To establish a method to assay 3 active components in pharmacy compounded terbinafine ointment simultaneously. Methods High performance liquid chromatography (HPLC) equipped with the ZORBAX SB-C8 (4.6 mm×250 mm, 5 μm) was used for the assay. The mobile phase was methanol-0.1% phosphoric acid (70∶30). The flow rate was 1.0 ml/min with the 248 nm detection wavelength, 10 μl injection volume and 30 ℃ column temperature. Results A good linear relationship was observed in the range of 20.4-204.0 µg/ml for terbinafine hydrochloride(r=0.999 7), 40.4-404.0 µg/ml for mupirocin(r=0.999 8), 2.02-20.20 µg/ml for mometasone furoate(r=0.999 7). The average recovery of each detected component in terbinafine ointment was 99.39%, 99.21%, 99.97% with the RSD 0.82%, 0.59%, 0.81%(n=9). Conclusion This method is simple, rapid and accurate. It can be used to detect the content of terbinafine, mupirocin and mometasone furoate in pharmacy compounded terbinafine ointment.
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Objective To establish an assay method for monohydroxy carbamazepine, the active metabolite of oxcarbazepine, in human plasma. Methods Ornidazole was used as the internal standard. Plasma samples were processed with methanol and analyzed by HPLC. The column was ZORBAX Eclipse XDB-C18(150 mm×4.6 mm, 5 μm) with the mobile phase of water-acetonitrile (80∶20, V/V) at a flow rate of 1.0 ml/min. Dual wavelength detection is applied. The detection wavelength of monohydroxy carbamazepine was set at 192 nm and ornidazole at 318 nm. Results There was an excellent liner relationship for monohydroxy carbamazepine from 2 to 50 μg/ml(r= 0.998 6). The limit of quantification was 2 μg/ml with the range of accuracy between 95.57% and 100.59%. The RSD of intra-day and inter-day precisions were less than 15%. The average extraction recovery rate of MHC and internal standard were in the range of 89.62% to 98.76%. The RSD of stability was less than 6%. Conclusion This method is specific, sensitive, and easy to operate. It is suitable for the clinical assay of monohydroxy carbamazepine in human plasma.
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Objective To prepare propranolol hydrochloride loaded cubosomes (PPL-Cubs) with high entrapment efficiency. Methods PPL-Cubs was prepared by pH gradient method. Pressure and cycles of high pressure homogenization, dosage of glyceryl monooleate and poloxamer 407 were optimized to prepare blank cubosomes with particle size and polydispersity index as the indexes. The influences of various factors, including exterior pH values, internal pH values, the ratio of carrier to drug, particle size and polydispersity index of blank cubosomes, incubation temperature and time, and drug concentration on the entrapment efficiency were investigated. Results The blank cubosomes with small particle size and polydispersity index was prepared under homogenization conditions of 900 bar for 7 cycles, glyceryl monooleate dosage of 25%, and poloxamer 407 dosage of 5%. PPL-Cubs showed high entrapment efficiency with exterior pH value of 8.5, internal pH value of 3.0, ratio of carrier to drug of 6∶1, incubation temperature of 20 ℃, and incubation time of 15 min, and drug concentration of 1%. The particle size and polydispersity index of blank cubosomes showed no influence on entrapment efficiency. Conclusion PPL-Cubs with high entrapment efficiency could be prepared under the pH gradient method.
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Objective To analyze the current situation of off-label drug use for tic disorder in a tertiary maternity and child hospital, so as to promote clinical safe and rational drug use. Methods Through the hospital information system, the pediatric outpatient prescriptions diagnosed with tic disorder from July 2019 to August 2020 were selected, and the prescriptions of off-label use was evaluated according to the 2020 off-label drug management regulations. Results A total 1251 pediatric prescriptions diagnosed with tic disorder were collected. The incidence of off-label drug use was 29.58%. The main types of off-label were over-indications and over-age. The main varieties of off-label drug use were risperidone tablets (47.84%) and aripiprazole tablets (43.74%). Conclusion The off-label use of drug for tic disorder in pediatric outpatient department of our hospital is relatively common,and it is necessary to standardize the management of off-label drug use to ensure rational drug use.
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Objective To establish a RP-HPLC method for determination of ketoconazole, mupirocin and mometasone furoate in compound ketoconazole ointment. Methods RP-HPLC was conducted on a Intersil ODS-3 column (250 mm×4.6 mm, 5 μm), with methanol-PBS with pH 5.5 (65:35) as the mobile phase and the column temperature was 45 ℃. The flow rate was 1.0 ml/min, and the detection wavelength was 248 nm. Results The methodological verification showed that ketoconazole, mupirocin and mometasone furoate had a good linearity (r≥0.9995). The inter/intra-day precisions were less than 3.0%, The recovery rates were between 90% and 108%. The stability and repeatability of RSD were also less than 3.0%, which met the requirements of method validation. The contents of the three components in three batches were determined by the new method. Conclusion The method is simple and reliable. It can provide a basis for the quality control of compound ketoconazole ointment and lay a foundation for its quality standard research.
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Objective To establish an UPLC-MS/MS method of voriconazole assay in human plasma for clinical therapeutic drug monitoring. Methods The plasma samples were treated with methanol to precipitate protein and the supernatants were assayed by UPLC-MS/MS. The chromatographic column was InertSustain C18 HP (3.0 mm×100 mm, 3 μm) with the mobile phase of water and acetonitrile solution (15:85) at 35 ℃ and 0.3 ml/min flow rate. ESI was used for Mass Spectrum in positive ion MRM mode with target ions m/z: 350.9/282.2(voriconazole) and m/z: 307.0/238.0(fluconazole). Results The linear range of voriconazole was 0.1–20 μg/ml (r=0.999 5). The lower limit of quantitation was 0.1 μg/ml. The extraction recovery was higher than 90%. RSDs of inter-day and intra-day were all lower than 10%. The plasma concentrations measured by this method were in the range of 0.97 to 18.7 μg/ml from 10 patients with hepatic insufficiency who were treated with voriconazole. Conclusion The established method was fast, accurate and sensitive。It can be applied for the therapeutic drug monitoring of voriconazole,and provided a good base for rationalized medication treatment in patients with hepatic insufficiency.
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Objective To explore the formulation and adjustment of nutritional therapy by nutrition support pharmacists in patient with acute prerenal failure complicated with urinary tract infection, and to provide a reference for nutritional therapy in such patient. Methods With nutrition support pharmacists participated in nutrition treatment management and case analysis of a patient with acute prerenal failure complicated with urinary tract infection, we explored the nutritional support treatment plan for this type of patient. Results Nutrition support pharmacists provided pharmaceutical care throughout the course for patient with acute prerenal failure and designed an individualized low-calorie and high-protein nutritional support treatment according to the change of patient's condition, to increase the patient's serum albumin level and maintain at 35 g/L, at the same time the infection was effectively controlled and the creatinine value decreased to normal. Conclusion Small-volume, low-calorie, high-protein nutritional support solution ≤1 000 ml, calorie intake is about 1, 000 kcal, and protein is maintained at 1.2 g/(kg·d) throughout the course of acute prerenal renal failure with urinary tract infected patients can obtain better clinical outcomes and prognosis, and can better maintain clinical operability, and fully improve the safety, effectiveness and economics of nutritional support treatment.
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Objective To analyze the quality of the hospital preparation magnesium sulfate oral solution by using capability sixpack. Methods By using the capability sixpack of Minitab, the content of magnesium sulfate in the magnesium sulfate oral solution was used as an indicator to determine whether the magnesium sulfate composition reached a controlled state during the production process and whether the production process of magnesium sulfate oral solution was stable. Results The content of magnesium sulfate and the production process of magnesium sulfate oral solution was under control, but there were potential disadvantages. Based on the concept of risk management philosophy, The failure model and effect analysis (FMEA) were applied to the prospective management of potential risks. Conclusion The application of the capability sixpack in the quality analysis of the hospital preparation of magnesium sulfate oral solution is helpful for us to discover the potential risks under the controlled state of the production process, which is beneficial to the improvement of the preparation production process and the assurance of the quality of the preparation.
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Objective To evaluate the effects of different solubilizing techniques on the in vitro dissolution and in vivo pharmacokinetics of Sirolimus (SRL). Methods Solid dispersions (SD), inclusion complex (IC), self-micro emulsifying drug delivery system (SMEDDS) and nano-structured lipid carrier (NLC) were selected as the solubilization technology for SRL. SRL-SMEDDS and SRL-NLC have obtained the optimal prescription in the previous studies. Additionally, the formulation process of SRL-SD and SRL-IC was screened by using inclusion rate and dissolution profiles as indicators. 0.4% SDS, water and buffer solutions with pH 1.2, 4.5, 6.8, 7.4 were used as dissolution media. The dissolution profile of the commercially available formulation Rapamune® and the lab-made solubilized preparations were investigated. The in vivo absorption of the above preparations was examined using a pharmacokinetic test in Beagle dogs. Results In 0.4% SDS, the dissolution of each preparation exceeded 80% in 2 h. In the medium of pH 1.2, the dissolution of SRL-SD could not be measured while the dissolution of IC, SMEDDS and NLC increased first and then decreased. In other media, the dissolution of the SRL was reduced. The SRL-IC showed the best dissolution without a significant decrease. The relative bioavailability of APIs, SRL-SD, SRL-IC, SRL-NLC and SRL-SMEDDS were 9.1%, 18.7%, 33.2%, 78.0%, and 97.6% respectively in vivo pharmacokinetic tests. Conclusion SD, SMEDDS, NLC, and IC can improve the in vitro dissolution and in vivo absorption of SRL. Among them, SMEDDS has the most significant improvement in the bioavailability of SRL.
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Objective Based on the data of gemcitabine adverse reactions (ADR), the characteristics and patterns of ADR occurrence were analyzed. The guidance for the rational clinical use of gemcitabine was provided. Methods From our information system, the patients treated by gemcitabine chemotherapy from September 2008 to September 2018 were selected and their related ADRs were summarized and statistically analyzed by using SPSS 18.0. Results Among the 750 cases, there were 312 ADRs related to gemcitabine treatment, of which the incidence of ADR was higher in female patients than in male patients (48.68% vs 36.77%) and the highest incidence in the age group of 50-69 years (44.14%). The patients with lower status (KPS) scores were more sensitive to chemotherapeutic drugs, and more likely to develop ADR. During the combination therapy, gemcitabine+paclitaxel chemotherapy had the highest incidence of ADR (61.54%) and the highest incidence of ADR in thymic carcinoma (62.50%), followed by hematological and reproductive system tumors (58.62% and 57.14%, respectively); ADR involvement in organs/systems is mainly caused by hematological toxicity. The bone marrow suppression is common, followed by digestive system damage. The major clinical symptoms were nausea and vomit. Conclusion Gemcitabine-related ADR has a large individualized difference and is affected by many factors. Chemotherapy should be used according to individual conditions to improve clinical safety and rational use of drugs.
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Objective To prepare a wound dressing using nitrocellulose as a membrane and optimize its formulation. Methods Partial analysis was performed on commercial available products. The wound dressings were prepared by using nitrocellulose as a film-forming material, benzyl alcohol as a bacteriostatic agent, castor oil as a plasticizer, isopropyl palmitate as a skin emollient, camphor as a fragrance, and isopropyl alcohol, ethyl acetate and butyl acetate as volatile solvent. The tensile strength, breakpoint elongation percentage, breathability and waterproof performance were tested and evaluated. Results The film-forming performance of the prepared liquid wound dressing was good. The final use amount of nitrocellulose was determined to be 6%. The use amount of plasticizer castor oil was determined to be 4%. Conclusion The prepared liquid wound dressing has good film-forming property, good mechanical property, good waterproof and certain breathability.
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Objective In order to improve the problems of poor water-solubility and low bioavailability of ocular tacrolimus, a cationic nanoemulsion in-situ gel of tacrolimus was developed and its drug release behavior in vitro was studied to provide a basis for further research. Methods Tacrolimus-loaded cationic nanoemulsion was prepared by high pressure homogenization and dispersed in poloxamer 407 and poloxamer 188 to prepare tacrolimus-loaded cationic nanoemulsion-based in-situ gel. The membraneless dissolution model was used to study the in vitro drug release behavior. Results The inverse glass bottle method was used to determine the gelation temperature. The optimal formulation of gel matrix was screened out as 26% poloxamer 407 and 12% poloxamer 188. The in vitro release results showed that the rate of gel dissolution determined the in vitro drug release. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel is successfully prepared. Its in vitro drug release is stable. It meets the requirement of ophthalmic formulation and shows good prospects for ocular application.