Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has bee...Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has been reported to show similar effectiveness in lowering IOP, compared with concomitant use of its component drugs, tafluprost and timolol. However, the difference in IOP-lowering effects between TTFC and concomitant use of tafluprost and gel-forming timolol is unknown. Hence, we conducted this switching study from tafluprost and gel-forming timolol to TTFC in glaucoma patients undergoing multi-drug therapy. Design: Multi-center, open-label, interventional clinical study. Methods: Twenty-eight patients (28 eyes;safety analysis set) with primary open-angle glaucoma and ocular hypertension, who had completed the 4-week-concomitant phase of tafluprost and gel-forming timolol, were treated for 8 weeks with TTFC. IOP, adherence, ocular surface safety, and the usability of ophthalmic solution were compared before and after switching. This study was approved by the ethics committees of Kitasato University Hospital and all other study sites. All patients provided written informed consent to participate. Results: IOP at 8 weeks after switching was significantly lower than before switching (P = 0.0001) in the efficacy analysis set (n = 24). The self-reported adherence rate remained high after switching;moreover, there was no meaningful change in ocular surface safety. Patient questionnaires regarding usability of medication revealed that 85.7% of patients preferred their instillation prescription after switching, including TTFC. Among the safety analysis set (n = 28), no adverse events were reported in relation to the study drug. Conclusion: TTFC showed greater IOP reduction than concomitant therapy. Thus, TTFC may be a better option in glaucoma patients than concomitant therapy.展开更多
AIM: To evaluate the quantitatively changes in lipid layer thickness(LLT) when 3% diquafosol eye drop is used for dry eye patients using the tear film interferometer. METHODS: A total 124 participants(32 males, 92 fem...AIM: To evaluate the quantitatively changes in lipid layer thickness(LLT) when 3% diquafosol eye drop is used for dry eye patients using the tear film interferometer. METHODS: A total 124 participants(32 males, 92 females;mean age, 28.9 y) diagnosed with dry eye disease(DED) received topical instillation of 4 ophthalmic solutions in one eye: diquafosol, normal saline, 0.1% sodium hyaluronate and 0.3% gatifloxacin, in a masked manner. LLT was measured using an interferometer at baseline and 20 min after the instillation of each ophthalmic solutions.RESULTS: Changes of LLT after instillation(nm, mean± standard error) were as follows: 12.6±2.0 for diquafosol(P<0.001), 1.2±2.2 for normal saline(P=0.301), 1.5±2.0 for hyaluronate(P=0.495), and 0.5±3.2 for gatifloxacin(P=0.884).CONCLUSION: Topical instillation of diquafosol increases tear film LLT in DED patients. Diquafosol 3% eye drop might be effective treatment option of evaporative DED with meibomian gland dysfunction.展开更多
AIM:To investigate the effectiveness of diquafosol ophthalmic solution 3%administered in Korean patients with dry eye disease in real-world clinical settings.METHODS:Diquafosol was administered for 8 wk to 3 patient g...AIM:To investigate the effectiveness of diquafosol ophthalmic solution 3%administered in Korean patients with dry eye disease in real-world clinical settings.METHODS:Diquafosol was administered for 8 wk to 3 patient groups who received diquafosol as add-on therapy to existing medication(Add group,n=150);received diquafosol only(Monotherapy group,n=196);or discontinued part of their existing medication in favor of diquafosol(Switch group,n=11).Tear break-up time(TBUT),cornea and conjunctival staining based on National Eye Institute/Industry scoring scheme,subjective symptoms using the Ocular Surface Disease Index(OSDI)questionnaire,and meibum quality and expressibility were evaluated at baseline,week 4,and week 8.RESULTS:The mean TBUT increased(from 3.46,3.92,and 5.84 s,respectively,to 5.15,5.53,and 8.59 s,respectively)and corneal staining score decreased(from 2.23,2.24,and 3.09,respectively,to 0.85,0.97,and 1.64,respectively)in a time-dependent manner from baseline to week 8 in all three groups.Conjunctival staining score,OSDI questionnaire,and meibum quality and expressibility improved over time from baseline to week 8 in the Add and Monotherapy groups,but differences were not statistically significant in the Switch group.CONCLUSION:Diquafosol improves subjective symptoms and objective signs in patients treated with existing medicines combined with diquafosol and treated solely with diquafosol.Diquafosol can be used as an effective therapeutic agent for dry eye disease or additionally applied in patients who have insufficient response to existing medicines.展开更多
There were several techniques determined for the analysis of citrate and citric acid mixtures in the pharmaceutical dosage forms. Titration methods, photometric and ion chromatographic methods were used for their dete...There were several techniques determined for the analysis of citrate and citric acid mixtures in the pharmaceutical dosage forms. Titration methods, photometric and ion chromatographic methods were used for their determination. These methods will restrict too many factors where the accurate quantification of citrate and citric acid is extremely challenging. Citric acid is the natural flavor used as a preservative for many pharmaceutical applications. Deformulation techniques used for the manufacturing of generic drugs require authentic data for their regulatory submissions. Simple accurate and reproducible validated method developed for the determination of citric acid and sodium citrate by titration followed by HPLC analysis. Free citric acid was determined by the titration method and total citric acid was determined by HPLC analysis. After subtracting the free citric acid from total citric acid content, citric acid present in the sodium citrate content was determined. Sodium citrate content was determined by applying sodium correction factor to the subtracted value of the citric acid. The results met all the validation parameters and the method was successfully measured the amount of citric acid and sodium citrate in the marketed ophthalmic/oral solutions.展开更多
Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic s...Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution(FC-TNL)has the ability to treat glaucoma by lowering the intraocular pressure(IOP)with great efficacy and improving patient compliance.However,the commercialized netarsudil dimesylate precipitated when the p H of the solution was above 5.4,or when maleic acid,the salt of commercial timolol maleate,was mixed with netarsudil dimesylate.Consequently,the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in p H 4.8–5.2 solution by synthesizing timolol mesylate.Next,the morphology of timolol mesylate was observed by scanning electron microscopy,differential scanning calorimetry,thermogravimetric analysis,and powder X-ray diffraction.The prepared FC-TNL showed good stability during refrigeration storage.Additionally,FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study.Importantly,oncedaily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells.The FC-TNL was stable,safe and effective,being a promising glaucoma therapeutic.展开更多
The validation of a simple, sensitive and specific agar diffusion bioassay, applying cylinder-plate method, for the determination of the antibiotic azithromycin in ophthalmic solutions is described. Using a strain of ...The validation of a simple, sensitive and specific agar diffusion bioassay, applying cylinder-plate method, for the determination of the antibiotic azithromycin in ophthalmic solutions is described. Using a strain of Bacillus subtilis ATCC 9372 as the test organism, azithromycin at concentrations ranging from 50.0 to 200.0 μg·mL -1 could be measured in 1.666 7 mg·mL -1 ophthalmic solutions. A prospective validation of the method showed that the method was linear (r=0.999 9) and precise (RSD=0.70) and accurate (it measured the added quantities). The results obtained by bioassay method could be statistically calculated by linear parallel model and by means of regression analysis and verified using analysis of variance (ANOVA). We conclude that the microbiological assay is satisfactory for quantification of azithromycin in ophthalmic solutions.展开更多
Background and Aim: Phacoemulsification surgery with intraocular lens implantation is routinely done under topical anaesthesia in many centres. No comparative study on the efficacy of number of drops of topical anaest...Background and Aim: Phacoemulsification surgery with intraocular lens implantation is routinely done under topical anaesthesia in many centres. No comparative study on the efficacy of number of drops of topical anaesthetics effective for phacoemulsification surgery has been done. This study was conducted to compare the efficacy of 2 drops versus 3 drops proparacaine 0.5% ophthalmic solution for phacoemulsification surgery. Methods: Patients with uncomplicated cataract undergoing phacoemulsification surgery were randomised into two groups. Group 1 (n = 53) received 3 drops of proparacaine 0.5% whereas group 2 (n = 47) received 2 drops of the same solution before the start of surgery. All the patients underwent phacoemulsification with foldable intraocular lens implantation. Each patient’s subjective experience of pain was measured using a 10 point Visual Analogue Pain Scale (VAS). Patient’s cooperation during the surgery was assessed using a 3 point score. Both the evaluating resident doctor and patients were blinded. Results: In group 1, 73.6% patients scored 0, 20.8% scored 1 and 5.7% scored 2 of VAS respectively and in group 2, 89.4%, 6.4%, 4.3% patients scored 0, 1 and 2 of VAS respectively. In patient cooperation, 90.1% and 9.4% patients in group 1 scored 1 and 2 respectively whereas 87.2% and 12.8% patients scored 1 and 2 respectively in group 2. No statistically significant difference in the mean VAS (P = 0.0.55) and patient cooperation score (P = 0.597) was found between the two groups. The mean VAS score was 1.24 ± 0.534 and the mean patient cooperation score was 1.11 ± 0.314. The mean total surgical time was 25.11 ± 2.68 minutes. No additional drops were required for either group. Conclusions: Topical anaesthesia with both 2 drops and 3 drops proparacaine 0.5% ophthalmic solution is effective for phacoemulsification with intraocular lens implantation. Additional anaesthesia may be unnecessary in these cases.展开更多
Background Nonselective muscarinic receptor antagonist, atropine, was believed to inhibit myopic progression. The purpose of this study was to determine the efficacy, through topical administration, of the M1-selectiv...Background Nonselective muscarinic receptor antagonist, atropine, was believed to inhibit myopic progression. The purpose of this study was to determine the efficacy, through topical administration, of the M1-selective muscarinic antagonist pirenzepine in preventing experimentally induced form-deprivation myopia in guinea pigs.Methods Fifty-three guinea pigs, which underwent monocular deprivation with their eyelids sutured, were divided into 6 groups. Three groups were treated with 1%, 2% or 4% pirenzepine ophthalmic solutions; the fourth group with atropine; the fifth with saline and the last group left untreated. Ocular refraction, in vivo biometric measurements and wet eye weight were collected before and after the experiment. All the eyes were finally enucleated for histopathological examination to evaluate the possible toxic effects on ocular structures.Results Animals untreated or treated with saline produced (-2.31±1.47) D and (-2.25±0.88) D of axial myopia respectively. Those treated with 1% pirenzepine ophthalmic solution produced relative myopia of (-1.63±0.48) D, and those under the treatment of 2% and 4% pirenzepine ophthalmic solution only developed a relative myopia of (-0.89±0.42) D and (-0.70±0.41) D (F=9.56, P<0.05). The significant reduction in myopia in 2% and 4% pirenzepine treated animals was caused by significantly less vitreous chamber elongation and axial elongation of the deprived eyes [2% group: (0.009±0.052) mm, 4% group: (0.006±0.078) mm] when compared with untreated, saline treated or 1% pirenzepine treated guinea pigs [(0.057±0.056) mm, (0.064±0.053) mm and (0.033±0.035) mm, respectively]. Histological examinations revealed no obviously toxic effects on the eyes treated with pirenzepine.Conclusion Topical administration of the M1-selective muscarinic antagonist, pirenzepine, can prevent induced form-deprivation myopia in guinea pigs by inhibiting axial elongation without obvious damage to ocular tissues.展开更多
文摘Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has been reported to show similar effectiveness in lowering IOP, compared with concomitant use of its component drugs, tafluprost and timolol. However, the difference in IOP-lowering effects between TTFC and concomitant use of tafluprost and gel-forming timolol is unknown. Hence, we conducted this switching study from tafluprost and gel-forming timolol to TTFC in glaucoma patients undergoing multi-drug therapy. Design: Multi-center, open-label, interventional clinical study. Methods: Twenty-eight patients (28 eyes;safety analysis set) with primary open-angle glaucoma and ocular hypertension, who had completed the 4-week-concomitant phase of tafluprost and gel-forming timolol, were treated for 8 weeks with TTFC. IOP, adherence, ocular surface safety, and the usability of ophthalmic solution were compared before and after switching. This study was approved by the ethics committees of Kitasato University Hospital and all other study sites. All patients provided written informed consent to participate. Results: IOP at 8 weeks after switching was significantly lower than before switching (P = 0.0001) in the efficacy analysis set (n = 24). The self-reported adherence rate remained high after switching;moreover, there was no meaningful change in ocular surface safety. Patient questionnaires regarding usability of medication revealed that 85.7% of patients preferred their instillation prescription after switching, including TTFC. Among the safety analysis set (n = 28), no adverse events were reported in relation to the study drug. Conclusion: TTFC showed greater IOP reduction than concomitant therapy. Thus, TTFC may be a better option in glaucoma patients than concomitant therapy.
文摘AIM: To evaluate the quantitatively changes in lipid layer thickness(LLT) when 3% diquafosol eye drop is used for dry eye patients using the tear film interferometer. METHODS: A total 124 participants(32 males, 92 females;mean age, 28.9 y) diagnosed with dry eye disease(DED) received topical instillation of 4 ophthalmic solutions in one eye: diquafosol, normal saline, 0.1% sodium hyaluronate and 0.3% gatifloxacin, in a masked manner. LLT was measured using an interferometer at baseline and 20 min after the instillation of each ophthalmic solutions.RESULTS: Changes of LLT after instillation(nm, mean± standard error) were as follows: 12.6±2.0 for diquafosol(P<0.001), 1.2±2.2 for normal saline(P=0.301), 1.5±2.0 for hyaluronate(P=0.495), and 0.5±3.2 for gatifloxacin(P=0.884).CONCLUSION: Topical instillation of diquafosol increases tear film LLT in DED patients. Diquafosol 3% eye drop might be effective treatment option of evaporative DED with meibomian gland dysfunction.
文摘AIM:To investigate the effectiveness of diquafosol ophthalmic solution 3%administered in Korean patients with dry eye disease in real-world clinical settings.METHODS:Diquafosol was administered for 8 wk to 3 patient groups who received diquafosol as add-on therapy to existing medication(Add group,n=150);received diquafosol only(Monotherapy group,n=196);or discontinued part of their existing medication in favor of diquafosol(Switch group,n=11).Tear break-up time(TBUT),cornea and conjunctival staining based on National Eye Institute/Industry scoring scheme,subjective symptoms using the Ocular Surface Disease Index(OSDI)questionnaire,and meibum quality and expressibility were evaluated at baseline,week 4,and week 8.RESULTS:The mean TBUT increased(from 3.46,3.92,and 5.84 s,respectively,to 5.15,5.53,and 8.59 s,respectively)and corneal staining score decreased(from 2.23,2.24,and 3.09,respectively,to 0.85,0.97,and 1.64,respectively)in a time-dependent manner from baseline to week 8 in all three groups.Conjunctival staining score,OSDI questionnaire,and meibum quality and expressibility improved over time from baseline to week 8 in the Add and Monotherapy groups,but differences were not statistically significant in the Switch group.CONCLUSION:Diquafosol improves subjective symptoms and objective signs in patients treated with existing medicines combined with diquafosol and treated solely with diquafosol.Diquafosol can be used as an effective therapeutic agent for dry eye disease or additionally applied in patients who have insufficient response to existing medicines.
文摘There were several techniques determined for the analysis of citrate and citric acid mixtures in the pharmaceutical dosage forms. Titration methods, photometric and ion chromatographic methods were used for their determination. These methods will restrict too many factors where the accurate quantification of citrate and citric acid is extremely challenging. Citric acid is the natural flavor used as a preservative for many pharmaceutical applications. Deformulation techniques used for the manufacturing of generic drugs require authentic data for their regulatory submissions. Simple accurate and reproducible validated method developed for the determination of citric acid and sodium citrate by titration followed by HPLC analysis. Free citric acid was determined by the titration method and total citric acid was determined by HPLC analysis. After subtracting the free citric acid from total citric acid content, citric acid present in the sodium citrate content was determined. Sodium citrate content was determined by applying sodium correction factor to the subtracted value of the citric acid. The results met all the validation parameters and the method was successfully measured the amount of citric acid and sodium citrate in the marketed ophthalmic/oral solutions.
基金financially supported by the Liao Ning Revitalization Talents Program(XLYC1902061)。
文摘Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution(FC-TNL)has the ability to treat glaucoma by lowering the intraocular pressure(IOP)with great efficacy and improving patient compliance.However,the commercialized netarsudil dimesylate precipitated when the p H of the solution was above 5.4,or when maleic acid,the salt of commercial timolol maleate,was mixed with netarsudil dimesylate.Consequently,the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in p H 4.8–5.2 solution by synthesizing timolol mesylate.Next,the morphology of timolol mesylate was observed by scanning electron microscopy,differential scanning calorimetry,thermogravimetric analysis,and powder X-ray diffraction.The prepared FC-TNL showed good stability during refrigeration storage.Additionally,FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study.Importantly,oncedaily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells.The FC-TNL was stable,safe and effective,being a promising glaucoma therapeutic.
文摘The validation of a simple, sensitive and specific agar diffusion bioassay, applying cylinder-plate method, for the determination of the antibiotic azithromycin in ophthalmic solutions is described. Using a strain of Bacillus subtilis ATCC 9372 as the test organism, azithromycin at concentrations ranging from 50.0 to 200.0 μg·mL -1 could be measured in 1.666 7 mg·mL -1 ophthalmic solutions. A prospective validation of the method showed that the method was linear (r=0.999 9) and precise (RSD=0.70) and accurate (it measured the added quantities). The results obtained by bioassay method could be statistically calculated by linear parallel model and by means of regression analysis and verified using analysis of variance (ANOVA). We conclude that the microbiological assay is satisfactory for quantification of azithromycin in ophthalmic solutions.
文摘Background and Aim: Phacoemulsification surgery with intraocular lens implantation is routinely done under topical anaesthesia in many centres. No comparative study on the efficacy of number of drops of topical anaesthetics effective for phacoemulsification surgery has been done. This study was conducted to compare the efficacy of 2 drops versus 3 drops proparacaine 0.5% ophthalmic solution for phacoemulsification surgery. Methods: Patients with uncomplicated cataract undergoing phacoemulsification surgery were randomised into two groups. Group 1 (n = 53) received 3 drops of proparacaine 0.5% whereas group 2 (n = 47) received 2 drops of the same solution before the start of surgery. All the patients underwent phacoemulsification with foldable intraocular lens implantation. Each patient’s subjective experience of pain was measured using a 10 point Visual Analogue Pain Scale (VAS). Patient’s cooperation during the surgery was assessed using a 3 point score. Both the evaluating resident doctor and patients were blinded. Results: In group 1, 73.6% patients scored 0, 20.8% scored 1 and 5.7% scored 2 of VAS respectively and in group 2, 89.4%, 6.4%, 4.3% patients scored 0, 1 and 2 of VAS respectively. In patient cooperation, 90.1% and 9.4% patients in group 1 scored 1 and 2 respectively whereas 87.2% and 12.8% patients scored 1 and 2 respectively in group 2. No statistically significant difference in the mean VAS (P = 0.0.55) and patient cooperation score (P = 0.597) was found between the two groups. The mean VAS score was 1.24 ± 0.534 and the mean patient cooperation score was 1.11 ± 0.314. The mean total surgical time was 25.11 ± 2.68 minutes. No additional drops were required for either group. Conclusions: Topical anaesthesia with both 2 drops and 3 drops proparacaine 0.5% ophthalmic solution is effective for phacoemulsification with intraocular lens implantation. Additional anaesthesia may be unnecessary in these cases.
文摘Background Nonselective muscarinic receptor antagonist, atropine, was believed to inhibit myopic progression. The purpose of this study was to determine the efficacy, through topical administration, of the M1-selective muscarinic antagonist pirenzepine in preventing experimentally induced form-deprivation myopia in guinea pigs.Methods Fifty-three guinea pigs, which underwent monocular deprivation with their eyelids sutured, were divided into 6 groups. Three groups were treated with 1%, 2% or 4% pirenzepine ophthalmic solutions; the fourth group with atropine; the fifth with saline and the last group left untreated. Ocular refraction, in vivo biometric measurements and wet eye weight were collected before and after the experiment. All the eyes were finally enucleated for histopathological examination to evaluate the possible toxic effects on ocular structures.Results Animals untreated or treated with saline produced (-2.31±1.47) D and (-2.25±0.88) D of axial myopia respectively. Those treated with 1% pirenzepine ophthalmic solution produced relative myopia of (-1.63±0.48) D, and those under the treatment of 2% and 4% pirenzepine ophthalmic solution only developed a relative myopia of (-0.89±0.42) D and (-0.70±0.41) D (F=9.56, P<0.05). The significant reduction in myopia in 2% and 4% pirenzepine treated animals was caused by significantly less vitreous chamber elongation and axial elongation of the deprived eyes [2% group: (0.009±0.052) mm, 4% group: (0.006±0.078) mm] when compared with untreated, saline treated or 1% pirenzepine treated guinea pigs [(0.057±0.056) mm, (0.064±0.053) mm and (0.033±0.035) mm, respectively]. Histological examinations revealed no obviously toxic effects on the eyes treated with pirenzepine.Conclusion Topical administration of the M1-selective muscarinic antagonist, pirenzepine, can prevent induced form-deprivation myopia in guinea pigs by inhibiting axial elongation without obvious damage to ocular tissues.
