The Yijing Buyang Huanwu Decoction combined with timolol maleate in the treatment of POAG / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To discuss the effect of Yijing Buyang Huanwu Decoction combined with timolol maleate eye drop on the blood supply and intraocular pressure in patients with primary open angle glaucoma(POAG). <p>METHODS:The 120 patients with POAG in our hospital from February 2018 to February 2020 were selected, they were divided into decoction group(<i>n</i>=60)and eye drop group(<i>n</i>=60)according to the randomly table. The eye drop group was treated with timolol maleate eye drop, and the decoction group was treated with Yijing Buyang Huanwu Decoction on the basis of the eye drop group, the eye blood supply \〖end diastolic velocity(EDV), peak systolic velocity(PSA), resistance index(RI)of central retinal artery(CRA)and posterior ciliary artery(PCA)\〗, intraocular pressure, visual acuity, visual field \〖mean sensitivity(MS), mean deviation(MD)\〗, efficacy and adverse reactions were compared between the two groups. <p>RESULTS: The EDV and PSA of the CRA and PCA and the visual acuity, MS in the Decoction group and eye drop group after treatment were significantly higher than those in the before treatment, the RI of the CRA and PCA and the intraocular pressure, MD in the Decoction group and eye drop group after treatment were significantly lower than those in the before treatment, the EDV and PSA of the CRA and PCA and the visual acuity, MS in the Decoction group after treatment were significantly higher than those in the eye drop group, the RI of the CRA and PCA and the intraocular pressure, MD in the Decoction group after treatment were significantly lower than those in the eye drop group(<i>P</i><0.05). The effective rate in the Decoction group was significantly higher than that in eye drop group(<i>P</i><0.05). There was no significant difference in adverse reactions between the Decoction group and eye drop group(<i>P</i>>0.05).<p>CONCLUSION: Yijing Buyang Huanwu Decoction combined with timolol maleate eye drop can effectively improve the blood supply, intraocular pressure and visual acuity, visual field of patients with POAG, it can improve the efficacy, and it has the good safety, it's worth for further clinical promotion.

Clinical study of Fuming tablet combined with Timolol Maleate eye drops in the treatment of open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the clinical study of Fuming tablet combined with timolol maleate eye drops in the treatment of open angle glaucoma.<p>METHODS: Totally 82(147 eyes)patients with open angle glaucoma who were treated in our hospital from April 2017 to July 2018 were selected as the research objects. According to the treatment methods, they were divided into control group and observation group, 41 cases in each group. Patients in the control group(72 eyes)were treated with timolol lecitrate eye drops, while patients in the observation group(75 eyes)were treated with Fuming tablets on the basis of the control group. The clinical efficacy of the two groups was observed. The intraocular pressure and hemorheology of the patients in the two groups were compared and analyzed before and after treatment.<p>RESULTS: After 12wk treatment, there was a significant difference in the total clinical effective rate(94.7% <i>vs</i> 80.6%)between the observation group and the control group(<i>P</i><0.05). And the intraocular pressure of both groups was significantly lower than that before and after 6wk of treatment(<i>P</i><0.05), and the intraocular pressure of the observation group was significantly lower than that of the control group(<i>P</i><0.05). The levels of PSV, EDV and RI in the control group were not significantly different from those before treatment(<i>P</i>>0.05); while the levels of PSV and EDV in the observation group were significantly higher than those before treatment(<i>P</i><0.05), and the levels of RI were significantly lower than those before treatment(<i>P</i><0.05). And there were significant differences in the levels of PSV, EDV and RI between two groups(<i>P</i><0.05). There was no significant difference in the total incidence of adverse reactions between two groups during the treatment(<i>P</i>>0.05).<p>CONCLUSION:Fuming tablet combined with timolol maleate eye drops can effectively improve the clinical efficacy of patients with open angle glaucoma. The effect of lowering intraocular pressure is obvious. At the same time, it has a good effect on the ocular hemorheology of patients with open angle glaucoma. This is a safe and reliable clinical treatment of open angle glaucoma.

Study of the therapeutic effect of oral propranolol combined with topical timolol maleate in the treatment of mixed maxillofacial hemangioma in infants / 口腔疾病防治

Objective@#To observe the treatment effect of oral propranolol combined with topical timolol maleate for infantile maxillofacial mixed hemangioma and provide evidence for clinical treatment.@*Methods@# Ninety-seven cases of infantile maxillofacial mixed hemangioma were enrolled. The cases were randomly divided into A and B groups: 50 cases in group A were treated with oral propranolol combined with topical timolol maleate, and 47 cases in group B were treated with oral propranolol only. The changes in the color, volume, and texture of the tumors were recorded before and after treatment, and color ultrasonography of the lesion area was performed. The follow-up time was 1-12 months. The differences in the curative effect, effective time and adverse reaction between the two groups were compared. @*Results @#The effective rate of group A was 92.0% (46/50) and that of group B was 74.5% (35/47), with a statistical significance (P < 0.05). The mean time of treatment in group A was 4.2 months and that in group B was 5.5 months. Compared with group B, the treatment time of group B was shorter (t=3.211, P < 0.05), and no serious adverse reactions occurred in both groups.@*Conclusion@#Oral propranolol combined with topical timolol maleate is effective in the treatment of mixed hemangioma of the maxillofacial region in infants.

Antimicrobial effectiveness of domestic timolol maleate eye drops / 中国药学杂志

OBJECTIVE: To screen out suitable antibacterial agent and reasonable dosage for timolol maleate eye drops. METHODS: According to the method of bacteriostatic effect test in Chinese Pharmacopoeia (Ch.P) 2015, the antimicrobial effectiveness of antimicrobial preservatives at different concentrations was tested to screen out the optimal agent and dosage. RESULTS: The eye drops added with ethyl hydroxybenzoate met the B-level requirements of bacteriostatic efficacy, which was the same as the sample without antibacterial agent, so ethyl hydroxybenzoate was not suitable as the antimicrobial preservative. The growth of five kinds of test microorganisms was inhibited effectively by 0.03 mg·mL-1 benzalkonium bromide. The timolol maleate eye drops with 0.03 mg·mL-1 benzalkonium bromide met the requirement of the quality standard. CONCLUSION: Benzalkonium bromide can be used as the antimicrobial preservative for timolol maleate eye drops.

Preparation and characterization of timolol maleate cubic nanoparticles for ocular administration / 药学学报

Timolol maleate cubic nanoparticles (TM-LCNPs) were prepared via fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by high-pressure homogenization. The optimal prescription was selected based on particle size and entrapment efficiency by orthogonal design method. Malvern particle sizer, polarized light microscopy, and differential scanning calorimetry were used to characterize the cubic nanoparticles. Commercial eye drops were used as a control for the release and corneal permeation experiment in vitro. Fluorescence imaging was used to observe the retention of Rhodamine B cubic nanoparticles (RhB-LCNPs) in rabbit cornea. The results indicated that the optimal prescription and preparation of TM-LCNPs was oil-water ratio (7:3), homogenous pressure (900 bar), the number of homogenizations (6) and drug loading (1%). Corneal permeability of TM-LCNPs was significantly higher than that of commercially available eye drops. The residence time in eyes was longer which suggested a sustained release behavior. The pathology result of rabbit corneal after multiple administration of TM-LCNPs showed that there was no apparent damage.

Usage and efficacy of timolol maleate eye drops in treatment of superficial infantile hemangioma / 中南大学学报(医学版)

Objective:To determine drug dose and usage of timolol maleate eye drops in the treatment of superficial infantile hemangioma.Methods:A total of 250 superficial hemangioma infants were recruited and assigned into 5 groups (n=50 for each group):an external application group and 4 exterior coating groups (2,4,6,8 times per day).We evaluated the therapeutic effect of different methods for drug application (external application or exterior coating) and the frequency for drug administration on superficial infantile hemangioma.Results:The external application group (twice a day and 0.5 hour per time) showed better effect than that in the exterior coating group with twice a day (P＜0.001).The difference in therapeutic effect between the exterior coating group with 6 times a day and exterior coating group with twice a day or with 3 times a day was significant (P＜0.001).The differences in drug efficacy were not found among the exterior coating group with 6 times a day,the exterior coating group with 8 times a day,or the external application group with twice a day (All P＞0.05).Conclusion:Drug dose may affect the therapeutic effect oftimolol maleate eye drops in superficial hemangioma infants,and exterior coating with 6 times a day may achieve the best curative effect.

Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles / Efeitos do maleato de timolol, do levobunolol e da apraclonidina sobre a pressão intraocular, o diâmetro pupilar, a pressão sanguínea e a frequência cardíaca, em cães da raça Beagle

The aim of this study was to evaluate changes in intraocular pressure (IOP), pupil size (PS), blood pressure (BP), heart rate (HR), and ECG variables (Pms wave PmV, PR interval, QRS complex, RMV wave and QT intervals) over time during the instillation of 0.5% timolol, 0.5% levobunolol and 0.5% apraclonidine in clinically normal dogs. Ten adult beagles were used. Baseline values were measured at 8a.m., 2p.m. and 8p.m., for three consecutive days. A waiting period of 10 days between the administrations of each drug was established. For 15 consecutive days, the drug being tested was instilled in one eye of each dog twice a day (7a.m. and 7p.m.). The parameters were evaluated at the aforementioned times on days 3, 6, 9, 12 and 15. Data were statistically compared using the Bonferroni test and one-way repeated measures analysis of variance (P<0.05). The Pearson test was used to evaluate any correlation between QT interval, HR and BP. The tested drugs did not find a decrease in IOP. A significant decreased in PS was observed in almost all dogs following levobunolol administration, relative to the control eye. A significant decrease in HR was observed on day 3 following levobunolol treatment, while apraclonidine induced an increase on day 15. Blood pressure was reduced in all measurement time points following apraclonidine treatment. A negative correlation between QT interval and HR was only observed in dogs treated with timolol. In conclusion, levobunolol was the only drug that induced significant alterations in PS. Apraclonidine was the only drug that induced systemic hypotension. Timolol was the only drug to that induced a negative correlation between QT and HR.(AU)

O objetivo deste estudo foi avaliar as mudanças na pressão intraocular (PIO), no diâmetro pupilar (DP), na pressão sanguínea (PS), na frequência cardíaca (FC) e nas variáveis eletrocardiográficas (onda Pms, PmV, intervalo PR, complexo QRS, onda RmV e intervalo QT), ao longo do tempo da instilação do timolol 0,5%, do levobunolol 0,5% e da apraclonidina 0,5% em cães clinicamente normais. Dez Beagles adultos compuseram o estudo. Valores basais foram mensurados às oito,, 14 e 20 horas, durante três dias consecutivos. Foi instituído um período de espera de 10 dias entre a administração de cada fármaco. Durante 15 dias consecutivos, um olho de cada animal recebeu uma gota de cada um deles, a intervalos de 12 horas (às sete e às 19 horas). Os parâmetros foram avaliados nos momentos acima referidos, nos dias três, seis, nove, 12 e 15. Os dados foram comparados estatisticamente empregando-se o teste de Bonferroni após análise de variância para medidas repetidas (P<0,05). Teste de Pearson foi utilizado para correlação entre o intervalo QT com a FC e a PS. Não se encontrou diminuição da PIO. Observou-se redução significativa do DP na quase totalidade dos animais que receberam levobunol, relativamente ao olho controle. Diminuição significativa da FC foi vista ao terceiro dia após a administração do levobunolol, enquanto apraclonidina induziu aumento no 15º dia. A pressão arterial foi reduzida em todos os momentos com a apraclonidina. Observou-se correlação negativa entre o intervalo QT e a FC apenas nos indivíduos tratados com o timolol. Em conclusão, levobunolol foi o único fármaco que induziu alterações significativas no DP. A apraclonidina foi o único fármaco que induziu hipotensão sistêmica significativa. O timolol foi o único a ensejar correlação negativa entre o intervalo QT e a FC.(AU)

Effect of dacryocystorhinostomy on systemic adverse effects of topical timolol maleate.

Purpose: To evaluate whether transformation of the naso-lacrimal passage as happens after dacryocystorhinostomy (DCR) operation has any effect on the systemic adverse effects of topically administered timolol maleate. Materials and Methods: Fifty otherwise healthy adult patients without any prior history of cardiac or pulmonary problems scheduled for elective DCR surgery received a drop of timolol maleate 0.5% on the healthy eye. This eye served as a control. Six weeks after successful DCR surgery, the operated eye received the same medication. Parameters compared included intraocular pressure (IOP), pulse rate, blood pressure and forced expiratory volume in the first second (FEV1) findings. Observations: Post DCR patients showed an increased incidence of reduced pulse rate and FEV1. Conclusion: Timolol maleate ophthalmic preparation should be used with caution in post-DCR patients.

Transdermal iontophoretic delivery of timolol maleate

Transdermal iontophoresis would be a promising method for the systemic delivery of water soluble and ionic drugs of relatively high molecular size, including peptides. The objective of the present study was to investigate the effect of biological variable such as guinea pig and human cadaver skin and other variables like drug concentration, current density on the transdermal iontophoretic transport of timolol maleate. The permeation profile of drug using solution and gel formulation was studied and compared. For better bioavailability, better patient compliance, and enhanced delivery, an iontophoretic drug delivery system of a timolol maleate matrix gel was formulated using Carbopol 974P. The study was conducted using silver-silver chloride electrodes across the guinea pig and human cadaver skin. Viscosity measurements and flux calculations indicated the suitability of the Carbopol 974P gel for transdermal iontophoretic delivery of timolol maleate. Anodal iontophoresis with silver-silver chloride electrode significantly increased the timolol maleate skin permeation as compared with the passive permeation study. The amount of timolol maleate transported during iontophoresis was significantly different among the different skins. However, iontophoretic gel formulations provided required flux of drug through human cadaver skin.

A iontoforese transdérmica seria um método promissor para a liberação sistêmica de fármacos solúveis em água e iônicos de relativamente elevado tamanho molecular, incluindo peptídeos. O objetivo do presente estudo foi investigar o efeito da variável biológica, tais como cobaia e pele de cadáver humano, e outras variáveis como concentração do fármaco, densidade de corrente sobre o transporte transdérmico iontoforético de maleato de timolol. Comparou-se o perfil de permeação do fármaco usando a formulação de solução e de gel. Para melhor biodisponibilidade, melhor adesão do paciente e liberação aprimorada, formulou-se sistema de liberação iontoforética gel de maleato de timolol usando Carbopol 974P. O estudo foi conduzido usando eletrodos de prata-cloreto de prata na cobaia e na pele de cadáver humano. Medidas de viscosidade e de fluxo indicaram a adequação do gel Carbopol 974 P para liberação iontoforética transdérmica do maleato de timolol. A iontoforese anódica com eletrodo de prata-cloreto de prata aumentou significativamente a permeação dérmica do maleato de timolol, comparativamente à permeação passiva. A quantidade de maleato de timolol transportado durante a iontoforese foi significativamente diferente entre as diferentes peles . No entanto, as formulações iontoforéticas de gel forneceram o fluxo necessário do fármaco através da pele de cadáver humano.

Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system.

Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.

Study on the Stability of 0.5% Timolol Maleate Eye Drops / 中国药房

OBJECTIVE:To study the stability of timolol maleate eye drops and predict its storage period at room temperature METHODS:Timolol maleate was determined by UV-spectrophotometry,initial average rate method was used in predicting the expiry term RESULTS:Stability of the 0 5% timolol maleate eye drops was not so good,expiry term predicted at 25℃ was only 70 days,while at 5℃ was as long as 1 2 years CONCLUSIONS:Initial average rate method is rapid,convenient and precise,so it is suitable for stability study of hospital preparations