Near-infrared (NIR) spectroscopy was applied to reagent-free quantitative analysis of polysaccharide of a brand product of proprietary Chinese medicine (PCM) oral solution samples. A novel method, called absorbance up...Near-infrared (NIR) spectroscopy was applied to reagent-free quantitative analysis of polysaccharide of a brand product of proprietary Chinese medicine (PCM) oral solution samples. A novel method, called absorbance upper optimization partial least squares (AUO-PLS), was proposed and successfully applied to the wavelength selection. Based on varied partitioning of the calibration and prediction sample sets, the parameter optimization was performed to achieve stability. On the basis of the AUO-PLS method, the selected upper bound of appropriate absorbance was 1.53 and the corresponding wavebands combination was 400 - 1880 & 2088 - 2346 nm. With the use of random validation samples excluded from the modeling process, the root-mean-square error and correlation coefficient of prediction for polysaccharide were 27.09 mg·L<sup>-</sup><sup>1</sup> and 0.888, respectively. The results indicate that the NIR prediction values are close to those of the measured values. NIR spectroscopy combined with AUO-PLS method provided a promising tool for quantification of the polysaccharide for PCM oral solution and this technique is rapid and simple when compared with conventional methods.展开更多
Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical...Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40°C/75% RH and 18 Months at 25°C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.展开更多
Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and...Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.展开更多
BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented...BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.展开更多
Stability indicating RP-UPLC technique was developed for the simultaneous quantification of glycopyrrolate, methylparaben, and propylparaben in glycopyrrolate oral solution. The method was established by using gradien...Stability indicating RP-UPLC technique was developed for the simultaneous quantification of glycopyrrolate, methylparaben, and propylparaben in glycopyrrolate oral solution. The method was established by using gradient UPLC and a Waters Acquity UPLC BEH C18, 100 mm 2.1 mm, i.d 1.7 μm particle size column with a gradient program of mobile phase A and mobile phase B with a flow rate of 0.25 mL/minute, UV wavelength detection at 222 nm, column temperature of 40°C, injection volume of 2 μL, mobile phase A contains 0.05% trifluoro acetic acid in water and Acetonitrile (90:10) v/v and mobile phase-B contains 0.05% trifluoro acetic acid in water and Acetonitrile (10:90) v/v. The current research describes a single UPLC method for developing an assay method for Glycopyrrolate Oral solution that includes Glycopyrrolate (Active), Methylparaben (Preservative), and Propylparaben (Preservative). The assay method was validated in accordance with ICH guidelines. The retention times of glycopyrrolate, methyl paraben and propylparaben were 6.051 min, 3.458 min and 8.095 min, respectively. Linearity range of glycopyrrolate, methyl paraben and propylparaben were in the range of 4 - 32 μg per mL, 35 - 290 μg per mL and 4 - 32 μg per mL, respectively. Recovery of glycopyrrolate, methylparaben and propylparaben ranged from 100.1% to 98.9%, 100.2% - 100.8%, and 100.2% - 100.8%. Validation of analytical method demonstrated that the method is suitable, specific, linear, accurate, precise, rugged and stability indicating for estimating three components in the pharmaceutical dosage form.展开更多
To observe the impact of Yupingfengsan Oral Liquid on the expression of IL-4 and IFN-<em>γ</em> in AR mice’s serum and expression level of nuclear factor—<em>κ</em>B (NF-<em>κ</em...To observe the impact of Yupingfengsan Oral Liquid on the expression of IL-4 and IFN-<em>γ</em> in AR mice’s serum and expression level of nuclear factor—<em>κ</em>B (NF-<em>κ</em>B) protein and gene in nasal mucosa. <strong>Method:</strong> Forty BALB/c mice were randomly divided into the normal group, model group, Yupingfengsan Oral Liquid group (6 g/kg) and Loratadine group, with 10 mice per group. AR mice model was established by OVA, and IL-4 and IFN-<em>γ</em> contents can be measured with ELISA. The morphological changes of nasal mucosa were observed by hematoxylin eosin (HE) staining and NF-<em>κ</em>B expression in the nasal mucosa of mice was tested with Real-Time PCR and Western blot. <strong>Results:</strong> Compared with the model group, the nasal symptoms in the Yupingfengsan Oral Liquid group and Loratadine group were obviously relieved. HE staining showed that there was a little inflammatory cell infiltration in the nasal mucosa of Yupingfengsan Oral Liquid group and Loratadine group and it was significantly reduced when compared with the model group. IL-4 level in the serum and expression of NF-<em>κ</em>B protein and gene in the nasal mucosa was consistent and it was decreased when compared with the model group (P < 0.01), but the IFN-<em>γ</em> level in the serum was increased (P < 0.01). <strong>Conclusion:</strong> Yupingfengsan Oral Liquid can improve the clinical symptoms and histopathological manifestations of AR mice sensitized by OVA, inhibit the NF-<em>κ</em>B expression, balance the percentage of Th1/Th2 cells, increase the IFN-<em>γ</em> level in the serum and decrease the IL-4 level.展开更多
AIM:To investigate the frequency,etiology,and current management strategies for diarrhea in newborn.METHODS:Retrospective,nationwide study involving 5801 subjects observed in neonatal intensive care units during 3 yea...AIM:To investigate the frequency,etiology,and current management strategies for diarrhea in newborn.METHODS:Retrospective,nationwide study involving 5801 subjects observed in neonatal intensive care units during 3 years.The main anamnesis and demographic characteristics,etiology and characteristics of diarrhea,nutritional and therapeutic management,clinical outcomes were evaluated.RESULTS:Thirty-nine cases of diarrhea(36 acute,3 chronic) were identified.The occurrence rate of diarrhea was 6.72 per 1000 hospitalized newborn.Etiology was defined in 29 of 39 newborn(74.3%):food allergy(20.5%),gastrointestinal infections(17.9%),antibiotic-associated diarrhea(12.8%),congenital defects of ion transport(5.1%),withdrawal syndrome(5.1%),Hirschsprung's disease(2.5%),parenteral diarrhea(2.5%),cystic fibrosis(2.5%),and metabolic disorders(2.5%).Three patients died due to complications related to diarrhea(7.7%).In 19 of 39 patients(48.7%),rehydration was performed exclusively by the enteral route.CONCLUSION:Diarrhea in neonates is a challenging clinical condition due to the possible heterogeneous etiologies and severe outcomes.Specific guidelines are advocated in order to optimize management of diarrhea in this particular setting.展开更多
文摘Near-infrared (NIR) spectroscopy was applied to reagent-free quantitative analysis of polysaccharide of a brand product of proprietary Chinese medicine (PCM) oral solution samples. A novel method, called absorbance upper optimization partial least squares (AUO-PLS), was proposed and successfully applied to the wavelength selection. Based on varied partitioning of the calibration and prediction sample sets, the parameter optimization was performed to achieve stability. On the basis of the AUO-PLS method, the selected upper bound of appropriate absorbance was 1.53 and the corresponding wavebands combination was 400 - 1880 & 2088 - 2346 nm. With the use of random validation samples excluded from the modeling process, the root-mean-square error and correlation coefficient of prediction for polysaccharide were 27.09 mg·L<sup>-</sup><sup>1</sup> and 0.888, respectively. The results indicate that the NIR prediction values are close to those of the measured values. NIR spectroscopy combined with AUO-PLS method provided a promising tool for quantification of the polysaccharide for PCM oral solution and this technique is rapid and simple when compared with conventional methods.
文摘Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40°C/75% RH and 18 Months at 25°C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.
基金This study was supported by grants from the National Natural Science Foundation of China(81972726,82273074 and 82372813)Dawn Project Foundation of Shanghai(21SG36)+2 种基金Shanghai Health Academic Leader Program(2022XD001)the Natural Science Foundation of Shanghai(22ZR1477900)Adjunct Talent Fund of Zhejiang Provincial People’s Hospital(2021-YT).
文摘Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.
基金Supported by Eunice Kennedy Shriver National Institute of Child Health&Human Development of the National Institutes of Health,No.1K08HD079674-01 and 1R41HD092133-01National Institute of Allergy and Infectious Diseases,No.1A21AI169282and VA Research Career Scientist Award,No.1IK6BX004835.
文摘BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.
文摘Stability indicating RP-UPLC technique was developed for the simultaneous quantification of glycopyrrolate, methylparaben, and propylparaben in glycopyrrolate oral solution. The method was established by using gradient UPLC and a Waters Acquity UPLC BEH C18, 100 mm 2.1 mm, i.d 1.7 μm particle size column with a gradient program of mobile phase A and mobile phase B with a flow rate of 0.25 mL/minute, UV wavelength detection at 222 nm, column temperature of 40°C, injection volume of 2 μL, mobile phase A contains 0.05% trifluoro acetic acid in water and Acetonitrile (90:10) v/v and mobile phase-B contains 0.05% trifluoro acetic acid in water and Acetonitrile (10:90) v/v. The current research describes a single UPLC method for developing an assay method for Glycopyrrolate Oral solution that includes Glycopyrrolate (Active), Methylparaben (Preservative), and Propylparaben (Preservative). The assay method was validated in accordance with ICH guidelines. The retention times of glycopyrrolate, methyl paraben and propylparaben were 6.051 min, 3.458 min and 8.095 min, respectively. Linearity range of glycopyrrolate, methyl paraben and propylparaben were in the range of 4 - 32 μg per mL, 35 - 290 μg per mL and 4 - 32 μg per mL, respectively. Recovery of glycopyrrolate, methylparaben and propylparaben ranged from 100.1% to 98.9%, 100.2% - 100.8%, and 100.2% - 100.8%. Validation of analytical method demonstrated that the method is suitable, specific, linear, accurate, precise, rugged and stability indicating for estimating three components in the pharmaceutical dosage form.
文摘To observe the impact of Yupingfengsan Oral Liquid on the expression of IL-4 and IFN-<em>γ</em> in AR mice’s serum and expression level of nuclear factor—<em>κ</em>B (NF-<em>κ</em>B) protein and gene in nasal mucosa. <strong>Method:</strong> Forty BALB/c mice were randomly divided into the normal group, model group, Yupingfengsan Oral Liquid group (6 g/kg) and Loratadine group, with 10 mice per group. AR mice model was established by OVA, and IL-4 and IFN-<em>γ</em> contents can be measured with ELISA. The morphological changes of nasal mucosa were observed by hematoxylin eosin (HE) staining and NF-<em>κ</em>B expression in the nasal mucosa of mice was tested with Real-Time PCR and Western blot. <strong>Results:</strong> Compared with the model group, the nasal symptoms in the Yupingfengsan Oral Liquid group and Loratadine group were obviously relieved. HE staining showed that there was a little inflammatory cell infiltration in the nasal mucosa of Yupingfengsan Oral Liquid group and Loratadine group and it was significantly reduced when compared with the model group. IL-4 level in the serum and expression of NF-<em>κ</em>B protein and gene in the nasal mucosa was consistent and it was decreased when compared with the model group (P < 0.01), but the IFN-<em>γ</em> level in the serum was increased (P < 0.01). <strong>Conclusion:</strong> Yupingfengsan Oral Liquid can improve the clinical symptoms and histopathological manifestations of AR mice sensitized by OVA, inhibit the NF-<em>κ</em>B expression, balance the percentage of Th1/Th2 cells, increase the IFN-<em>γ</em> level in the serum and decrease the IL-4 level.
文摘AIM:To investigate the frequency,etiology,and current management strategies for diarrhea in newborn.METHODS:Retrospective,nationwide study involving 5801 subjects observed in neonatal intensive care units during 3 years.The main anamnesis and demographic characteristics,etiology and characteristics of diarrhea,nutritional and therapeutic management,clinical outcomes were evaluated.RESULTS:Thirty-nine cases of diarrhea(36 acute,3 chronic) were identified.The occurrence rate of diarrhea was 6.72 per 1000 hospitalized newborn.Etiology was defined in 29 of 39 newborn(74.3%):food allergy(20.5%),gastrointestinal infections(17.9%),antibiotic-associated diarrhea(12.8%),congenital defects of ion transport(5.1%),withdrawal syndrome(5.1%),Hirschsprung's disease(2.5%),parenteral diarrhea(2.5%),cystic fibrosis(2.5%),and metabolic disorders(2.5%).Three patients died due to complications related to diarrhea(7.7%).In 19 of 39 patients(48.7%),rehydration was performed exclusively by the enteral route.CONCLUSION:Diarrhea in neonates is a challenging clinical condition due to the possible heterogeneous etiologies and severe outcomes.Specific guidelines are advocated in order to optimize management of diarrhea in this particular setting.
