Influence of indometacin on the level of platelet microparticles in patients with post-endoscopic retrograde cholangiopancreatography pancreatitis / 中华消化内镜杂志

To observe the effect of indomethacin suppository 100 mg before endoscopic retrograde cholangiopancreatography (ERCP) on the level of platelet microparticles (PMPs) in patients with post-ERCP pancreatitis (PEP). A total of 191 patients receiving ERCP were collected from June 2019 to October 2020 in the First Affiliated Hospital of Anhui Medical University and were randomly divided into the indometacin group ( n=96) and the control group ( n=95) by random number table method. The indometacin group received 100 mg indometacin suppositories before ERCP and the control group received placebo of equal quality. Levels of PMPs before operation, 3 hours and 24 hours after operation were measured by flow cytometry. The levels of IL-1, IL-6 and TNF-α in the plasma before ERCP, 3 hours and 24 hours after ERCP were also detected. The incidence of PEP in the indometacin group was 5.21% (5/96), which was significantly lower than that in the control group [13.68% (13/95), P=0.044]. The preoperative PMPs level in the indometacin group (1 910.01/μL) was slightly lower than that in the control group (2 351.87/μL) with no significant difference ( P>0.05). The PMPs levels in the indometacin group 3 hours and 24 hours after ERCP (1 671.47 /μL, 862.74/μL) were significantly lower than those of the control group (2 443.75/μL, 2 536.76/μL, both P<0.05). Inflammatory cytokines including IL-1, IL-6 and TNF-α showed the same tendency. Indometacin can reduce the incidence of PEP, for the reason that indometacin may decrease the levels of PMPs.

Characterization of Indomethacin Enteric-coated Dropping Pills / 中国药师

Objective: To study the status of indomethacin (IDM) in IDM enteric-coated dropping pills and its interaction with PEG 6000.Methods: IDM, PEG 6000, their physical mixture and IDM enteric-coated dropping pills were respectively studied by DSC, IR, X-ray diffraction and SEM.Results: In the map of DSC, the endothermic peak of IDM enteric-coated dropping pills disappeared at 164℃, and the endothermic peak of PEG 6000 at 57℃ shifted forward.In the map of IR, the carbonyl stretching vibration peak of IDM in IDM enteric-coated dropping pills disappeared, and a new peak appeared at 1 680 cm-1.In the map of X-ray diffraction, there was no diffraction peak in IDM enteric-coated dropping pills.SEM showed the morphology of IDM in the base was much smaller than that of IDM raw material.Conclusion: IDM in IDM enteric-coated dropping pills is dispersed in the matrix with an amorphous or molecular form, and there is hydrogen bond between IDM and PEG 6000.

Simultaneous Determination of Two Ingredients in Indometacin and Furazolidone Suppositories by HPLC / 中国药师

Objective: To establish an HPLC method for the simultaneous determination of two ingredients in indometacin and furazolidone suppositories.Methods: The analysis was performed on an XTerra(R) RP18 column (250 mm×4.6 mm, 5 μm) with gradient elution of methanol and 0.01 mol·L-1 potassium dihydrogen phosphate-triethylamine (100∶0.02) at the flow rate of 1.0 ml·min-1.The column temperature was 30 ℃ and the detection wavelength was 263 nm.The injection volume was 10 μl.Results: The peaks of furazolidone and indometacin were successfully separated.The linear range of calibration curves was 5.12-81.87 μg·ml-1 (r =1.0000) and 3.78-60.45 μg·ml-1 (r =1.0000), respectively.The average recovey was 99.6% (RSD =1.5%, n =6) and 100.3% (RSD =1.6%, n =6), respectively.The limit of quantification (LOQ) was 0.02 μg·ml-1 and 0.05 μg·ml-1, respectively.Conclusion: The established method is validated to be suitable for the quality control of indometacin and furazolidone suppositories.

Simultaneous Determination of Two Components in Furazolidone, Indometacin and Cuscohygrinolis α-Acetylbenzoacetate Suppositories by HPLC with Dual Wavelength Detection / 中国药师

Objective:To establish an analytical method for the determination of furazolidone and indometacin in furazolidone, in-dometacin and cuscohygrinolis α-acetylbenzoacetate suppositories by HPLC. Methods: The separation was performed on a ZORBAX Extend-C18 (250 mm × 4. 6 mm,5μm) column. The mobile phase was acetonitrile and 0. 035 mol·L-1 potassium phosphate monobas-ic aqueous solution (adjusting pH to 3. 0 with acetic acid) with gradient elution. The flow rate was 1. 0 ml·min-1, and the detection wavelengths were set at 364 nm and 318 nm. The column temperature was 30℃ and the injection volume was 20 μl. Results:Under the selected chromatographic conditions, the two components showed good linearity within the range of 0.005-0.05 mg·ml-1(r=0. 9999). The limit of detection was 20 ng·ml-1 and 26 ng·ml-1, respectively. The limit of quantitation was 70 ng·ml-1 and 90 ng·ml-1, respectively. The average recovery was 99. 4％(RSD=0. 6％, n=9)and 99. 4％(RSD=0. 3％,n=9),respectively. Conclusion:The method is simple, rapid and specific, and the results are accurate and reliable. The method can be used for the de-termination of the two components in furazolidone, indometacin and cuscohygrinolis α-acetylbenzoacetate suppositories.

Pharmacokinetics of Indometacin Enteric-coated Dropping Pills in Beagle Dogs / 中国药师

Objective:To study the pharmacokinetics of indometacin (IDM) enteric-coated dropping pills.Methods:Beagle dogs were used as the experimental animals and the marketed IDM enteric-coated tablets were applied as the control,the pharmacokinetics of IDM enteric-coated dropping pills was studied after a single oral administration.DAS software was used for the model fit and parameter calculation,and the bioequivalence was also evaluated.Results:Both IDM enteric-coated dropping pills and tablets were fitted a one-compartment model.Compared with those of IDM enteric-coated tablets,the Cmax,Tmax,AUC0-∞and Tlag of IDM enteric-coated dropping pills all showed notable differences (P<0.05),and the former two increased significantly,and the latter two were shortened significantly.The relative bioavailability of the dropping pills was (121.0±7.7)%.Conclusion:Compared with IDM enteric-coated tablets,IDM enteric-coated dropping pills are with significantly enhanced absorption and shortened lag time,which is worthy of further studies and development.

Determination of Related Substance in Indometacin Enteric-coated Tablet by Improving HPLC / 中国药房

OBJECTIVE:To improve HPLC for the contents determination of 2-methyl-5-methoxy-indole-3-acetic acid(impuri-ty Ⅰ) and 4-chlorobenzoic (impurity Ⅱ) in Indometacin enteric-coated tablet. METHODS:The column was Phenomenex Phe-nyl-Hexyl with mobile phase of 10 g/L acetic acid solution- acetonitrile(gradient elution)at a flow rate of 1.0 ml/min,the detec-tion wavelength was 254 nm,column temperature was 40℃,injection volume was 20 μl. RESULTS:The linear range was 0.262 2-5.243 0 μg/ml for impurity Ⅰ(r=0.999 8)and 0.252 5-5.050 0 μg/ml for impurity Ⅱ(r=0.999 8);the limits of quanti-tation were 1.12 ng and 0.48 ng,limits of detection were 0.340 ng and 0.146 ng,respectively;RSDs of precision,stability and re-producibility tests were lower than 2%;recoveries were 99.71%-100.52%(RSD=0.28%,n=9) and 100.84%-102.14%(RSD=0.47%,n=9). CONCLUSIONS:The method is accurate and rapid,and can be used for the contents determination of impurity Ⅰand impurityⅡin Indometacin enteric-coated tablet.

Effects of Indometacin on Apoptosis and Proliferation of Cervical Cancer Hela Cell / 中国药房

OBJECTIVE:To study the effects of indometacin on apootosis and proliferation of cervical cancer Hela cell. METH-ODS:Hela cell was cultured in vitro as study object,and cultured with 0(blank control),200,400,600,800 and 1 000 μmol/L indometacin for 24,48 and 72 h. The inhibitory rate of indometacin to the proliferation of Hela cells was detected by MTT assay. After treated with 0(blank control),400,600 and 800 μmol/L indometacin for 24 h,the change of cellular morphology was ob-served by invert microscope;cell cycle phase and apoptosis were analyzed by flow cytometry. RESUITS:Indometacin of 600, 800,1 000μmol/L could inhibit the proliferation of Hela cell,which was positively correlated to drug concentration and time. Com-pared with blank control,indometacin could induce that Hela cell transformed from polygonous to round in appearance,and result-ed in cell apoptosis and necrosis;the proportion of cells at G0/G1 phase increased,while the proportion of cells at S phase reduced;the apoptotic rate of cells raised. CONCLUSIONS:Indometacin could inhibit the proliferation of Hela cell,block cell cycle at G0/G1 phase and induce apoptosis.

Protective effect of olvanil against sulfur mustard-induced cutaneous injury / 国际药学研究杂志

Objective: To study the protective effects of olvanil on sulfur mustard (SM)-induced cutaneous injury. Methods: To establish mouse ear model of SM-induced cutaneous injury, KM mice right ears were exposed to 5 μl of 32 g/L or 128 g/LSM, respectively. Then we evaluated the protective effect of olvanil against SM-induced cutaneous injury with these two concentrations. For mice exposed to 32 g/L SM, olvanil (0.125, 0.25 and 0.5 mg/ear, topically) or indometacin (indomethacin, 10 mg/kg, po) were administrated 20 min or 30 min before SM exposure, respectively. After 24 h SM exposure, ear tissue was harvested and weighted, and the histopathological analysis was conducted. Similarly, for mice exposed to 128 g/L SM, olvanil (0.25 mg/ear, topically) or indomethacin (10 mg/kg, po) were administrated, and ear tissue was harvested and weighted. Results: Olvanil significantly inhibited 32 g/L SM-induced ear edema, cutaneous inflammation and necrosis, while no influence were observed on 128 g/L SM-induced cutaneous injury. Conclusion: Olvanil shows remarkable protective effect on cutaneous injury induced by SM of low concentration.

Reports of Clinical Pharmacists Participating in the Diagnosis and Treatment of Two Cases of Drug-in-duced Diseases / 中国药师

Objective:To explore the role of clinical pharmacists in the diagnosis and treatment of drug-induced diseases. Meth-ods:Clinical pharmacists analyzed the abnormal changes in the patients and looked for drug factors during the ward round with physi-cians. Results:Clinical pharmacists found drug-induced diseases and irrational drug use, and proposed the solutions accepted by phy-sicians. Conclusion:Clinical pharmacists should actively participate in the diagnosis and treatment of drug-induced diseases.

Preparation and Drug Release in vitro of Indometacin Enteric Dropping Pills / 中国药师

Objective:To prepare indometacin ( IDM) enteric dropping pills and study the drug release in vitro. Methods:Using PEG6000 as the base, the optimal formula and preparation process of IDM dropping pills were screened by an orthogonal design. IDM dropping pills were coated by polyacrylic resin II as the enteric coating material. Compared with the marketed IDM enteric tablets, the drug release of IDM enteric dropping pills in vitro was studied using a suspended basket method. Results:The optimal preparation con-ditions of IDM dropping pills were as follows:the ratio of IDM and base was 1∶3, the dropping speed was 65 drops/min, the dropping temperature was 90℃ and the temperature of the cooling solvent was 5℃. IDM dropping pills and the marketed tablets were both with little drug release in acidic solvent. In pH 6. 8 phosphate buffer solution, IDM enteric dropping pills showed much quicker drug release than the marketed enteric tablets (P<0. 05). Conclusion:IDM enteric dropping pills exhibit enteric effect and quick drug release in vitro, which are valuable to be studied further.

Clinical Observation of Self-made Headache Prescription on Migraine without Aura / 浙江中医药大学学报

[Objective] To observe the therapeutic effects of headache prescription on migraine without aura. [Methods] 54 patients with migraine were randomly divided into two groups: Patients in control group(n=27) were treated by nimodipine and flunarine,etc; Patients in treatment group(n=27) were treated by self made headache prescription, the treatment period was both 5 days; then determine efficacy.[Results] 27 patients in treatment group had 6 cases in clinical cure,14 in excellent,6 in effect,1 in vain, the clinical total effective rate of Chinese medicine group was 96.30%,while,27 patients in treatment group had 2 cases in clinical control ed,8 in excellent,9 in effect,8 in vain, the clinical total effective rate of Chinese medicine group was 70.37%. The difference between the two groups had the remarkable significance.[Conclusion] The therapeutic effects of headache prescription on migraine without aura has better therapeutic effects on migraine.

Efecto secuestrador del D-002 sobre radicales hidroxilo en mucosa gástrica / Scavenger effect of D-002 on hydroxyl radicals in the gastric mucosa

Introducción: el agente causal de la ulceración gástrica está asociado al desequilibrio entre factores agresivos y defensivos que actúan sobre la mucosa gástrica. El D-002, mezcla de seis alcoholes alifáticos primarios superiores purificada de la cera de abejas, produce efectos gastroprotectores mediados por múltiples mecanismos y reducción de la peroxidación lipídica en la mucosa gástrica. Objetivo: determinar si el D-002 es capaz de capturar el radical hidroxilo añadido in vitro o generado in vivo en ratas con úlcera gástrica inducida por indometacina. Métodos: En la experiencia in vitro el D-002 se añadió a concentraciones entre 0,9 y 1 000 mg/mL. En la experiencia in vivo las ratas se distribuyeron en seis grupos: un control negativo y cinco que recibieron indometacina: un control positivo tratado con el vehículo, tres con D-002 (5, 25, y 100 mg/kg, respectivamente, p.o.) y otro con omeprazol (20 mg/kg i.p.). Los tratamientos se administraron una hora (vehículo y D-002) o 30 min (omeprazol), respectivamente, antes de inducir las úlceras. En ambas experiencias se tomaron alícuotas de mucosa gástrica, y se determinó el daño a la 2-desoxirribosa por el radical hidroxilo. Resultados: la administración oral del D-002, no in vitro, protegió a la 2-desoxirribosa del daño oxidativo de modo marcado, significativo y dependiente de la dosis con respecto al control positivo. Conclusiones: los resultados indican que la capacidad del D-002 (25 y 100 mg/kg) administrado por vía oral para secuestrar el radical hidroxilo, generado en la mucosa gástrica por la indometacina, pudiera contribuir a sus efectos antioxidantes y gastroprotectores sobre el daño que los antiinflamatorios no esteroideos producen sobre la mucosa gástrica.

Introduction: the etiology of the gastric ulceration is associated to the imbalance between aggressive and defensive factors acting upon the gastric mucosa. D-002, a mixture of 6 higher primary alcohols purified from the beeswax, cause some multiple mechanism-mediated gastroprotective effects and decrease of lipid peroxidation in the gastric mucosa. Objective: to determine whether D-002 can scavenge the in vivo added or in vivo generated hydroxyl radical in rats with indometacin-induced gastric ulcer or not. Methods: For the in vitro experiment, D-002 was added at concentrations 0.9 and 1 000 mg/mL For the in vivo experiment, the rats were randomized into 6 groups: one negative control, and five indometacin-treated groups as follows a positive excipient-treated control, three under D-002 treatment (5, 25 or 100 mg/kg, respectively, p.o.), and another group treated with Omeprazole (20 mg/kg i.p.). These lines of treatment were given 1 hour (excipient and D-002) or 30 min (Omeprazole) prior to inducing the ulcers. In both experiments, aliquots from the gastric mucosa were taken and the damage infringed to 2-deoxiribose by the hydroxyl radical was determined. Results: oral administration of D-002, rather than in vitro addition, significantly protected 2-desoxiribose from the oxidative damage depending on the dosage as compared to the positive control. Conclusions: these results indicate that the ability of the orally administered D-002 (25 and 100 mg/kg) to scavenge the hydroxyl radical endogenously generated on the gastric mucosa by indometacin could contribute to its antioxidant and gastroprotective effects against the damage that the non-steroidal anti-inflammatory drugs carry to the gastric mucosa.

Should we definitively abandon prophylaxis for patent ductus arteriosus in preterm new-borns?

Although the prophylactic administration of indomethacin in extremely low-birth weight infants reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage, it does not appear to provide any long-term benefit in terms of survival without neurosensory and cognitive outcomes. Considering the increased drug-induced reduction in renal, intestinal, and cerebral blood flow, the use of prophylaxis cannot be routinely recommended in preterm neonates. However, a better understanding of the genetic background of each infant may allow for individualized prophylaxis using NSAIDs and metabolomics.

Treatment of pentoxifyline on collagen-induced arthritis in rats / 中华风湿病学杂志

Objective To evaluate the efficacy and safety of pentoxifyline (PTX) on the treatment of collagen-induced arthritis in rats. Methods Wistar rat arthritis model was induced by bovine Ⅱ collagen (BⅡC) . The rats were randomly divided into four groups including normal control group, CIA control group treated with normal saline, indometaein group and PTX group. The body weight, the hind paw volumes, the arthritic index of all rats at different time points were observed and measured. At the end of the experiment, the radiographic changes and the synovial pathology score of rat ankle joints were evaluated to analyze the treatment role of PTX on CIA inflammation. Results The collagen-induced arthritis model was induced successfully at 11~13 days after first immunization with type Ⅱ collagen. After administration, the rat weights of PTX group were higher than that of CIA group (P<0.01) and no significant difference was found between PTX group and normal control group since week three. The degree of swelling of ankle joints in PTX group was decreased since the 17th day. At week five, the volumes of hind paw in PTX group and indometacin group was not different from that in normal control group (P>0.05). Compared with CIA group, the degree of synovial swelling of PTX group and indometacin group was decreased, synovial proliferation and inflammatory cell infiltrations was mild, and vascular hyperplasia and pannus was significantly declined. No cartilage erosion and necrosis was found. The pathological score of PTX group and indometacin group was significantly decreased(P<0.01). The parenchyma of ankle joint was swollen and no osteoporosis and bone erosion was found in PTX group and indometacin group. Conclusion PTX can ameliorate the symptoms and inhibit the swollen of rat arthritis. It is effective and with good safety profile.

Preparation and Quality Control of Rapid-disintegrating Oral Tablets of Indometacin / 中国药房

OBJECTIVE:To prepare rapid-disintegrating oral tablets of indometacin and establish a method for its quality control.METHODS:The formula of the oral tablets was optimized by orthogonal test with the formula quality of CMS-Na(A),L-HPC(B),MCC(C),manniton(D) as factors,and the disintegrating time as index.The content of indometacin was determined by ultraviolet spectrophotometry.RESULTS:The optimal formula of the tablets was the following,A∶B∶C∶D=5∶5∶50∶5.The preparation was white in color and its quality was up to the related standard specified in Chinese Pharmacopeia (2005 edition) in identification.The linear range of indometacin was 2.08～41.6 ?g?mL-1 (r=0.999 9).The average recovery was 99.3%.The intra-day RSD=0.53% and inter-day RSD=0.74%.CONCLUSION:The preparation is simple and feasible in preparation process,and controllable in quality.

Protective Effect of Nimesulide on Experimental Gastric Ulcer in Rats / 中国药房

OBJECTIVE: To study the protective effects of nimesulide, a COX- 2 selective inhibitor on experimental gastric ulcer in rats. METHODS: The gastric ulcer model was established in rats by intragastric administration them with indometacin, 5 min later, which were assigned to receive nimesulide at different dosages ( 200, 100, and 50mg? kg- 1) , 6h later, all the rats were sacrificed. The primary outcome measures were the area of ulcer, levels of SOD, MDA, and GSH in sera and gastric mucosa. RESULTS: As compared with model group, in nimesulide ( at different dosage) groups, the area of ulcer was markedly decreased, level of MDA was decreased while activities of SOD and GSH were increased ( P

Compound Indometacin Tincture Treat Eczema on Hand and Foot of 48 Cases of Children / 浙江中医药大学学报

[Objective]To explore the effective method for eczema on hand and foot of children.[Method]Apply Compound Indometacin Tincture(CIT) to 48 cases of eczema on hand and foot of children.[Result]30 cases were cured,8 cases had marked effect,5 effective,5 cases no effect,the total effective rate was 89.58%.[Conclusion]CIT has good therapeutic effect on eczema on hand and foot of children.Its effect is similar to that of steroid hormone.

Effect of Indomethacin suppositories on albumin concentration and insulin resistance of post-operation patients with serious intra-abdominal infection / 中国现代普通外科进展

Objective:To evaluate the effect of Indomethacin suppositories on albumin concentration and insulin resistance of post-operation patients with serious intra-abdominal infection.Methods:38 post-operation patients with serious intra-abdominal infection were divided into two groups randomly.One as treatment group(n=19)and the other as control group(n=19).Albumin,blood glucose,fasting insulin concentration were measured At 72 hours after the operation and 144 hours.Insulin resistance index was calculated using the homeostasis model assessment(HOMA).Finally,the results of two groups were analyzed.Results:The albumin concentration of Indomethacin group at 72 hours was significantly higher than that after 72 hours,Insulin resistance of 144 hours was lower than the control group(P0.05).Conclusion:Postoperative abdominal infection using indomethacin suppository can significantly reduce insulin resistance,and significantly reduced the decomposition of albumin.

Kinetic of vascular and cellular alterations in the carrageenin-induced peritonitis in Gallus gallus. Effect of steroidal and non-steroidal antiinflamatory drugs / Cinética das alterações vasculares e celulares na peritonite induzida pela Carragenina em gallus gallus. Efeito de drogas antiinflamatórias esteroidais e não esteroidais

The kinetic of vascular and cellular alterations in the carrageenin-induced peritonitis was investigated (500 mcg) in Gallus gallus and the effect of the pre-treatment with dexamethasone (0.5; 1.0 or 2.0 mg/kg), indomethacin (2.0; 4.0 or 8.0 mg/kg), pyroxiean (20.0; 40.0 or 80.0 mg/kg), given by oral route 30 minutes before the inflammatory stimulus. It was observed that the highest increase in both vascular permeability and leucocyte accumulation ocurred respectively 150 minutes and 4 hours after the carrageenin injection. Polymorphonuclear leukocytes were the predominant cell type in the exudate obtained 2 and 4 hours after the stimulus. An equilibriun between polymorphonuclear and mononuclear cells was observed with 24 hours of inflammation and the latter cell type was predominant after 48 hours. The pre-treatment with indomethacin and pyroxiean significantly (p 0.05) inhibited the vascular permeability increase but not the leukocytes counts. Dexamethasone was significantly reduced both vascular permeability increase and leukocyte accumulation. These results suggest that eicosanoids have a role in the vascular permeability increase but it is less relevant in the leuchocyte chemotaxis in carrageenin-induced acute inflammation in fowls. The vascular permeability increase and cellular migration are independent phenomena when the effect of antiinflammatory drugs are concerned

Neste trabalho investigou-se a cinética das alterações vasculares e celulares na peritonite induzida pela carragenina (500 mcg) em Gallus gallus e o efeito do pré-tratamento com dexametasona (0,5; 1,0 ou 2,0 mg/kg), indometacina (2,0; 4,0 ou 8,0 mg/kg), ou piroxicam (20,0; 40,0 ou 80,0 mg/kg), administrados por via oral, 30 minutos antes do estímulo lesivo. Observou-se que os máximos aumento de permeabilidade vascular e acúmulo de leucócitos ocorreram 150 min. e 4 h, após a aplicação do irritante, respectivamente. Os leucócitos polimorfonucleares foram o tipo celular predominante no exsudato após 2 e 4 h, equilibraram-se com as mononucleares após 24 h, predominando o último tipo celular após 48 h. O maior acúmulo de células polimorfo e mononucleares ocorreu após 4 h e 24 h, respectivamente. O pré-tratamento com indometacina ou piroxicam inibiu significativamente (p 0,05) o aumento de permeabilidade vascular mas não o acúmulo de leucócitos, 150 min. e 4 h após o estímulo lesivo, respectivamente. A dexametasona foi efetiva em reduzir significativamente (p 0,05) ambos os componentes. Os resultados sugerem que os eicosanóides participem ativamente dos fenômenos vasculares mas são de pouca relevância na quimiotaxia de leucócitos no processo inflamatório agudo induzido pela carragenina cm Gallus gallus. Os achados indicam que quando o efeito de drogas antiinflamatórias é consid

Formulation design and vitro evaluation of self-microemulsifying drug delivery system / 中成药

90% in 20 min and more higher than the control tablets or capsule. CONCLUSION: The optimum formulation suits to slightly soluble drugs with different o/w distribution coefficient.It can provide reference for application of the SMEDDS the practical cases.