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英文药名: AZORGA Combination Ophthalmic Suspension(Brinzolamide/Timolol Maleate)
中文药名: 布林佐胺/马来酸噻吗洛尔组合眼悬浮液
生产厂家：爱尔康日本公司
アゾルガ配合懸濁性点眼液
药物分类名称
碳酸酐酶抑制剂/β阻滞剂复合
青光眼·高眼压治疗
商標名
AZORGA Combination Ophthalmic Suspension
1.一般名
ブリンゾラミド (Brinzolamide)
化学名
(R )-4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H -thieno[3,2,e ]-1,2-thiazine-6-sulfonamide 1,1-dioxide
構造式
分子式
C12H21N3O5S3
分子量
383.51
融点
約131℃
性状
白色至淡黄色白色结晶或粉末，微溶于甲醇，几乎不溶于乙醇（99.5），不溶于水。
2.一般名
チモロールマレイン酸塩 (Timolol Maleate)
化学名
(2S)-1-[(1,1-Dimethylethyl)amino]-3-(4-morpholin-4-yl-1,2,5-thiadiazol-3-yloxy)propan-2-ol monomaleate
構造式
分子式
C13H24N4O3S・C4H4O4
分子量
432.49
融点
約197℃ (分解)
性状
它是一种白色至微黄色的白色结晶粉末。它易溶于乙酸（100），微溶于水或乙醇（99.5）。溶于0.1mol/L盐酸试剂溶液中。
药物药理学
1.布林佐胺
（1）眼内压降低作用
在诱导激光小梁成形术高眼压12只食蟹猴，滴入每天两次的1％悬浮液布林佐胺，给药1,3,6和12小时后24.7眼压％，35.8％，26.5％和23.5％。
（2）碳酸酐酶抑制作用
该产品对II型碳酸酐酶（CA-II）具有高亲和力，并显示出比I型碳酸酐酶约多95倍的结合能力。
（3）作用机制
碳酸酐酶（CA）存在于许多全身组织中并且催化CO 2水解和碳酸脱水的可逆反应。人眼中有多种碳酸酐酶同工酶，但是布林唑胺选择性抑制最活跃的CA-II。布林佐胺抑制CA-II在眼睛的睫状体，以减少形成HCO 3-@的速率-，因此，通过抑制输送到Na+和水，后房抑制房水的分泌结果据信降低了眼内压。
2.马来酸噻吗洛尔
（1）眼内压降低作用
在由糜蛋白酶诱导的眼内压升高试验诱导的眼内压升高和水负荷中，已经观察到滴注马来酸噻吗洛尔显着抑制眼内压升高。
（2）β-受体阻断作用
通过静脉内注射马来酸噻吗洛尔和口服给药，大鼠，狗和猫中的异丙肾上腺素（异丙肾上腺素）的心率，心肌收缩性和心输出量的增加被显着抑制，并且效果显着高于普萘洛尔3 两倍，十倍。
（3）作用机制
已经提出马来酸噻吗洛尔在猴子中的眼内压降低作用主要是由于房水产生的抑制。
适应症
青光眼，高眼压症
用法与用量
每天一次，每天两次。
临床结果
1.在日本进行的临床研究（优越性试验）
在301例青光眼患者（原发性开角型青光眼，脱屑性青光眼）或高眼压症患者的III期双重屏蔽对比研究中，在观察期间，噻吗心安0.5％滴眼液滴眼2次，每天2次，持续4周 ，作为主要评价项目的11点（滴注后2小时）的8点，在治疗期间将该产品（一天两次）或对照药物（0.5％噻吗洛尔滴眼液）滴注8周 眼药水组的眼压变化量显着大于对照组（最小均方组间差异：-1.7mmHg，p <0.0001，非配对t检验），0.5％噻吗心胺滴眼液 验证了滚降效果的优越性（以基线眼压值作为协变量的迭代测量协方差分析）（表1）。
2.在日本进行的临床研究（非劣性试验）
在309例青光眼患者（原发性开角型青光眼，脱屑性青光眼，色素性青光眼）或高眼压症患者的III期双重屏蔽比较研究中，0.5％噻吗心胺滴眼液每日两次给药4周 在治疗期间用该产品（每日两次）或用对照剂（每天两次布林佐胺1％眼用溶液和每日两次噻吗洛尔0.5滴眼液的组合疗法）滴注该产品（每日两次）后， 作为评价项目的眼压变化量（2小时滴注）的剂量强度之差的97.5％单侧置信区间的上限为0.4mmHg，单侧置信区间的上限为0.4mmHg，验证了低于+1.1mmHg的数值和降低该药物组合疗法的眼内压降低效果的非劣性（重复测量以基线眼压值作为协变量的协方差分析）（表2）。
3.在日本进行的临床试验（长期给药试验）
在125例青光眼患者（原发性开角型青光眼，正常眼压性青光眼，脱屑青光眼）或高眼压患者的III期开放标签试验中，停用预处理药物后，在52周的滴注期间，每个观察周期的眼内压从4周到52周的变化是-5.7mmHg到-4.1mmHg，并且在12个月时显示自基线的眼内压降低（p<0.0001，相应的t检验）（重复测量方差分析）（图3）。
包装
5mL×10本
制造和销售（进口）
诺华制药公司[联盟]爱尔康制药公司
注：以上中文资料不够完整，使用者以原处方资料为准。
完整说明书附件：http://www.info.pmda.go.jp/go/pack/1319821Q1027_2_02/
Azorga: "Carbonic anhydrase inhibitor+beta blocker" in the second formulation Eye drops
On November 19, 2013, brinzolamide/timolol maleate salt(trade name Azorga compound suspended ophthalmic solution), a therapeutic agent for glaucoma and ocular hypertension, was listed on the drug price and released. Ezetimibe already has manufacturing approval on September 20th. This product contains blinzolamide (trade name Eisopt), a carbonic anhydrase inhibitor, which has been conventionally used as a component of eye drops, and timolol maleate (trade name Timoptol, Rismon et al.) Which is a β blocker It is eye drops. Eye drop once a day, twice a day.
Glaucoma is a disease in which the optic nerve is damaged due to elevated intraocular pressure, the visual field gradually lacks, and there is a danger of blindness if left untreated. In Japan, one in twenty people over the age of 40 has developed, and it is the number one cause of visual impairment. Among glaucoma, there are many untreated diseased patients because there are also many types (intraocular pressure glaucoma) that the intraocular pressure does not rise, so early detection and early treatment are said to be important.
The only established treatment for glaucoma disease and ocular hypertension is to lower intraocular pressure, and as a therapeutic agent to be used, a pro
Among glaucoma patients, it is difficult to control intraocular pressure for a long time with only one eye drop, and there are many examples using two drugs in combination. However, when two or more eye drops are to be used in combination, it is necessary to open the interval between eye drops as the drug solution overflows from the lacrimal pouch when the eye drops are used successively, which causes a forgetting to drop eye drops etc. , Compliance reduction occurred, which was a problem.
The Azorga-containing suspending ophthalmic solution suppresses aqueous humor production and reduces intraocular pressure by the carbonic anhydrase inhibitor and beta blocker compounded. Because it is a combination drug, it can be applied only once to two kinds of medicine, improvement of compliance can be expected, and patient convenience is high.
Four formulations have been released as compound eye drops to be used in the treatment of glaucoma and ocular hypertension. Three of them are preparations containing prostaglandin derivative and beta blocker (timolol maleate), and the other formulation is dorzolamide hydrochloride of carbonic anhydrase inhibitor, timolol maleate of beta blocker and "Cosopto" is blended. Azorga will be a combination eye drop of a carbonic anhydrase inhibitor and a beta blocker, the second following cosoth.
The combined effects of these two agents with different mechanisms of action have been confirmed by multiple clinical trials both in Japan and abroad. Overseas, since approval in Europe (EU) in 2008, as of May 2013, it has been approved in more than 100 countries and regions.
In drug use, some side effects are recognized in 10.6% in the domestic phase III trial, so it is necessary to pay sufficient attention. The main side effects are eye irritation (3.5%), punctate keratitis (3.2%), dysgeusia (1.4%) and the like, and serious side effects include ocular pemphigus, bronchial asthma, dyspnea, respiratory failure , Heart block, congestive heart failure, cerebral ischemia, cardiac arrest, cerebrovascular accident, systemic lupus erythematosus. |
