CN101068573A - 局部用奈帕芬胺制剂 - Google Patents

局部用奈帕芬胺制剂 Download PDF

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CN101068573A
CN101068573A CNA200580041442XA CN200580041442A CN101068573A CN 101068573 A CN101068573 A CN 101068573A CN A200580041442X A CNA200580041442X A CN A200580041442XA CN 200580041442 A CN200580041442 A CN 200580041442A CN 101068573 A CN101068573 A CN 101068573A
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Abstract

本发明公开了奈帕芬胺的局部用混悬液组合物。该组合物尤其适合于局部眼科施用。

Description

局部用奈帕芬胺制剂
发明背景
本发明涉及可局部施用的奈帕芬胺眼科制剂。本发明的制剂是混悬液组合物。
奈帕芬胺也被称为2-氨基-3-苯甲酰基苯基乙酸。奈帕芬胺和3-苯甲酰基苯基乙酸的其他酰胺和酯衍生物治疗眼科炎症和疼痛的局部用途公开在U.S.专利5475034中。根据’034专利，含有3-苯甲酰基苯基乙酸衍生物的组合物可配制为各种局部可施用的眼科组合物，如溶液、混悬液、凝胶或软膏。该组合物任选含有防腐剂如苯扎氯胺和增稠剂如卡波姆、羟乙基纤维素或聚乙烯醇。
发明概述
本发明的组合物是奈帕芬胺的水性混悬液组合物。该组合物含有0.09-0.11％(w/v)奈帕芬胺。该组合物基本上由奈帕芬胺、卡波姆、非离子性表面活性剂、张力调节剂、pH-调节剂、纯化水和任选的防腐剂和鳌合剂组成。
发明详述
除非另外指示，所有成分的浓度以％重量/体积单位(％w/v)表示。
奈帕芬胺是已知化合物。其可通过已知方法制备。参见例如U.S.专利5475034和4313949。本发明的组合物含有0.09-0.11％奈帕芬胺，优选0.1％奈帕芬胺。
除奈帕芬胺外，本发明的混悬液组合物还含有卡波姆作为增稠剂或物理稳定性增强剂。适合用于本发明的卡波姆还被称为“羧乙烯基聚合物”或羧聚乙烯。它们自Noveon，Inc.(Cleveland，Ohio)市售可得，以商品名Carbopol(卡波普)销售。卡波普聚合物是交联丙烯酸类聚合物。它们与烯丙基蔗糖或烯丙基季戊四醇交联。卡波普共聚物是丙烯酸的聚合物，其用C10-30烷基丙烯酸酯修饰并与烯丙基季戊四醇交联。用于本发明组合物中的优选的卡波姆是与烯丙基蔗糖或烯丙基季戊四醇交联的丙烯酸聚合物，其以Carbopol974P市售可得。本发明组合物中卡波姆的浓度通常为0.4-0.6％，优选0.5％。
本发明的组合物还含有眼科可接受的非离子性表面活性剂。已知许多眼科可接受的非离子性表面活性剂。适合的非离子性表面活性剂包括但不限于泰洛沙泊；聚氧乙烯失水山梨酯如聚山梨酯20、聚山梨酯60和聚山梨酯80；聚乙氧基化蓖麻油Cremophor EL；聚乙氧基化的氢化蓖麻油如HCO-40；和泊洛沙姆。最优选的表面活性剂是泰洛沙泊。在泰洛沙泊的情况下，表面活性剂通常含量为0.001-0.05％，优选0.01％。
除了奈帕芬胺、卡波姆和非离子性表面活性剂之外，本发明的组合物还含有眼科可接受的张力调节剂。眼科可接受的张力调节剂包括但不限于金属氯化物盐和非离子性张力调节剂如甘露醇。优选的金属氯化物盐为人类泪液中可见的那些，如氯化钠、氯化钾、氯化钙和氯化镁。本发明组合物中所含张力调节剂的量是足以使组合物的同渗质量摩尔浓度为约250-350mOsm/kg、优选270-315mOsm/kg的量。最优选氯化钠和甘露醇的组合。对于其中张力调节剂是氯化钠和甘露醇的组合的最优选的实施方案，氯化钠的量优选为0.3-0.5％，甘露醇的量为2-3％，最优选的氯化钠的量为0.4％，最优选的甘露醇的量为2.4％。
本发明的组合物的pH为70-7.8。优选地，组合物的pH为7.3-7.7，最优选7.5。组合物含有眼科可接受的pH调节剂，以获得所需pH。眼科可接受的pH调节剂是已知的，包括但不限于盐酸(HCl)和氢氧化钠(NaOH)。
本发明的组合物任选含有眼科可接受的防腐剂成分。眼科可接受的防腐剂成分是已知的，包括但不限于卤化苄烷铵(benzalkonium halide)如苯扎氯胺、聚季铵盐-1(polyquaternium-1)和二氧化氯。最优选苯扎氯胺和聚季铵盐-1。在苯扎氯胺的情况下，防腐剂的含量优选为0.001-0.01％，最优选0.005％。
鳌合剂也任选包含在本发明的混悬液组合物中。适合的鳌合剂包括乙二胺四乙酸二钠；乙二胺四乙酸三钠；乙二胺四乙酸四钠；哌嗪五乙酸盐(diethyleneamine pentaacetate)。最优选乙二胺四乙酸二钠。如果包括鳌合剂，其通常含量为0.001-0.1％。在乙二胺四乙酸二钠的情况下，鳌合剂优选以0.01％的浓度存在。
以下实施例意欲阐述而非限制本发明。
                         实施例1
制备以下表1A中所示制剂，并比较它们的体外角膜渗透率。按照Ke等人，Inflammation，24(4)：371-384(2000)所述方法，使用新鲜分离的兔角膜于灌注浴中评价角膜渗透率。角膜渗透结果示于表1B中。
                          表1A
                  制剂
  A   B
  成分   ％(w/v)   ％(w/v)
  奈帕芬胺   0.1   0.1
  Carbopol 974P   0.35   0.5
  氯化钠   0.4   0.4
  甘露醇   2.4   2.4
  泰洛沙泊   0.01   0.01
  乙二胺四乙酸二钠   0.01   0.01
  苯扎氯胺   0.01   0.01
  NaOH/HCl   适量至pH7.5   适量至pH7.5
  纯化水   适量至100   适量至100
                 表1B
  制剂   角膜渗透率(nM/min)(平均±SD)
  A   10.7±0.6(n＝4)*
  B   17.2±1.2(n＝4)*
*统计学显著差异(p＜0.001)。
                         实施例2
制备以下表2A中所示制剂并比较它们的体外角膜渗透率。角膜渗透结果示于表2B中。
                            表2A
                      制剂
  C   D   E
  成分   ％(w/v)   ％(w/v)   ％(w/v)
  奈帕芬胺   0.3   0.3   0.3
  Carbopol 974P   0.35   0.35   0.5
  氯化钠   0.4   0.4   0.4
  甘露醇   2.4   2.4   2.4
  泰洛沙泊   0.01   0.01   0.01
  乙二胺四乙酸二钠   0.01   0.01   0.01
  苯扎氯胺   0.005   0.01   0.01
  NaOH/HCl   适量至pH7.5   适量至pH7.5   适量至pH7.5
  纯化水   适量至100   适量至100   适量至100
                 表2B
  制剂   角膜渗透率(nM/min)(平均±SD)
  C   63.8±8.9(n＝4)*
  D   65.2±15.0(n＝3)*
  E   61.4±10.5(n＝5)*
*制剂C、D和E之间无显著性差异。
                         实施例3
制备以下表3A中所示制剂并比较它们的体外角膜渗透率。角膜渗透结果示于表3B中。
                            表3A
                     制剂
  F   G   H
  成分   ％(w/v)   ％(w/v)   ％(w/v)
  奈帕芬胺   0.1   0.1   0.1
  Carbopol 974P   0.35   0.35   0.5
  氯化钠   0.4   0.4   0.4
  甘露醇   2.4   2.4   2.4
  泰洛沙泊   0.01   0.01   0.01
  乙二胺四乙酸二钠   0.01   0.01   0.01
  苯扎氯胺   0.005   0.01   0.01
  NaOH/HCl   适量至pH7.5   适量至pH7.5   适量至pH7.5
  纯化水   适量至100   适量至100   适量至100
                表3B
  制剂   角膜渗透率(nM/min)(平均±SD)
  F   13.9±4.4(n＝4)*
  G   9.9±5.87(n＝4)*
  H   20.8±2.4(n＝5)*
*制剂F和H之间存在统计学显著差异(p＝0.02)
*制剂G和H之间存在统计学显著差异(p＝0.007)
制剂F和G之间无统计学显著差异。
                         实施例4
制备以下表4A中所示制剂并比较它们的体外角膜渗透率。角膜渗透结果示于表4B中。
                           表4A
                 制剂
  I   J
  成分   ％(w/v)   ％(w/v)
  奈帕芬胺   0.1   0.1
  Carbopol 974P   0.35   0.5
  氯化钠   0.4   0.4
  甘露醇   2.4   2.4
  泰洛沙泊   0.01   0.01
  乙二胺四乙酸二钠   -   -
  苯扎氯胺   -   -
  NaOH/HCl   适量至pH7.5   适量至pH7.5
  纯化水   适量至100   适量至100
                  表4B
  制剂   角膜渗透率(nM/min)(平均±SD)
  I   12.0±1.9(n＝4)*
  J   18.3±2.2(n＝4)*
*统计学显著差异(p＝0.005)。
实施例1-4的数据证明：对于奈帕芬胺浓度为0.3％的组合物而言，卡波姆的量对于角膜渗透率没有统计学显著的影响。相比之下，对于奈帕芬胺浓度为0.1％的组合物，卡波姆的量具有统计学显著影响。对于含有0.1％奈帕芬胺的组合物，卡波姆浓度为0.5％的组合物与含有卡波姆浓度0.35％的组合物相比，具有优异的角膜渗透率。
                  实施例5
              局部眼科组合物
  成分   ％(w/v)
  奈帕芬胺   0.1
  苯扎氯胺   0.005
  Carbomer 974P   0.5
  泰洛沙泊   0.01
  乙二胺四乙酸二钠   0.01
  甘露醇   2.4
  氯化钠   0.4
  NaOH/HCl   适量至pH7.3-7.7
  纯化水   适量至100
本发明已经参考某些优选实施方案进行描述；但是，应该理解其可以以其他具体形式或其变体实施，只要不偏离其精神和实质特征即可。上述实施方案因此被视为全方位阐述性的而非限制性的，本发明的范围由所附权利要求而非上文描述所示。

Claims (20)

1.可局部施用眼科组合物，其组成基本如下：
a)0.09-0.11％(w/v)奈帕芬胺；
b)0.4-0.6％(w/v)卡波姆；
c)非离子性表面活性剂；
d)张力调节剂，其量足以使组合物的同渗质量摩尔浓度为250-350mOsm/kg；
e)pH调节剂，其量足以使组合物的pH为7.0-7.8；和
f)水，
其中组合物任选含有选自防腐剂和鳌合剂的成分。
2.权利要求1的组合物，其中组合物包含0.1％(w/v)奈帕芬胺。
3.权利要求1的组合物，其中组合物包含0.5％(w/v)卡波姆。
4.权利要求1的组合物，其中卡波姆是与烯丙基蔗糖或烯丙基季戊四醇交联的丙烯酸聚合物。
5.权利要求1的组合物，其中非离子性表面活性剂是泰洛沙泊。
6.权利要求5的组合物，其中组合物包含0.01％(w/v)泰洛沙泊。
7.权利要求1的组合物，其中张力调节剂选自金属氯化物盐和甘露醇。
8.权利要求7的组合物，其中张力调节剂包含氯化钠和甘露醇。
9.权利要求8的组合物，其中组合物包含0.3-0.5％(w/v)氯化钠和2-3％(w/v)甘露醇。
10.权利要求9的组合物，其中组合物包含0.4％(w/v)氯化钠和2.4％(w/v)甘露醇。
11.权利要求1的组合物，其中pH调节剂选自盐酸和氢氧化钠。
12.权利要求1的组合物，其中组合物的pH为7.3-7.7。
13.权利要求1的组合物，其中组合物含有防腐剂和鳌合剂。
14.权利要求1的组合物，其中防腐剂选自卤化苄烷铵；聚季铵盐-1和二氧化氯。
15.权利要求1的组合物，其中防腐剂是苯扎氯胺。
16.权利要求15的组合物，其中组合物包含0.005％苯扎氯胺。
17.权利要求1的组合物，其中鳌合剂选自乙二胺四乙酸二钠；乙二胺四乙酸三钠；乙二胺四乙酸四钠；和哌嗪五乙酸盐。
18.权利要求17的组合物，其中组合物包含0.001-0.1％(w/v)乙二胺四乙酸二钠。
19.治疗患者眼科炎性病症的方法，包括向患者局部施用权利要求1的组合物。
20.可局部施用的眼科组合物，其组成基本如下：
a)0.1％(w/v)奈帕芬胺；
b)0.5％(w/v)卡波姆；
c)0.01％(w/v)泰洛沙泊；
d)0.4％(w/v)氯化钠；
e)2.4％(w/v)甘露醇；
f)pH调节剂，其量足以使组合物的pH为7.3-7.7；
g)0.005％(w/v)苯扎氯胺；
h)0.01％乙二胺四乙酸二钠；和
i)纯化水。
CNA200580041442XA 2004-12-02 2005-12-02 局部用奈帕芬胺制剂 Pending CN101068573A (zh)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104490861A (zh) * 2014-11-21 2015-04-08 三明欣茂药业有限公司 一种缓释型奈帕芬胺眼用制剂
CN106963730A (zh) * 2016-12-22 2017-07-21 广州仁恒医药科技股份有限公司 高度稳定的奈帕芬胺眼用药物组合物
CN107024550A (zh) * 2016-12-21 2017-08-08 广州仁恒医药科技股份有限公司 奈帕芬胺眼用药物组合物的质控方法
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Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI358290B (en) 2004-12-02 2012-02-21 Alcon Inc Topical nepafenac formulations
US20060257487A1 (en) * 2005-05-10 2006-11-16 Alcon, Inc. Suspension formulations of nepafenac and other ophthalmic drugs for topical treatment of ophthalmic disorders
EP1906916B1 (en) * 2005-05-10 2008-10-29 Alcon Inc. Ophthalmic suspension comprising an ophthalmic drug, a poloxamine and a glycol tonicity-adjusting agent, use of said composition for the manufacture of a medicament for treating ophthalmic disorders
TW200812575A (en) * 2006-04-28 2008-03-16 Alcon Inc Formulations containing amide derivatives of carboxylic acid NSAIDs for topical administration to the eye
US20080057022A1 (en) * 2006-08-30 2008-03-06 Erning Xia Ophthalmic Pharmaceutical Compositions and Uses Thereof
CA2687717A1 (en) * 2007-05-24 2008-12-18 Aciex Therapeutics, Inc. Formulations and methods for treating dry eye
TWI531362B (zh) * 2008-07-21 2016-05-01 艾爾康股份有限公司 具有治療劑遞送能力之眼科裝置
TW201023912A (en) 2008-12-05 2010-07-01 Alcon Res Ltd Pharmaceutical suspension
WO2010101971A1 (en) * 2009-03-03 2010-09-10 Alcon Research, Ltd. Pharmaceutical composition for delivery of receptor tyrosine kinase inhibiting (rtki) compounds to the eye
WO2010101989A1 (en) * 2009-03-03 2010-09-10 Alcon Research, Ltd. PHARMACEUTICAL COMPOSITION FOR DELIVERY OF RECEPTOR TYROSINE KINASE INHIBITING (RTKi) COMPOUNDS TO THE EYE
WO2011068872A2 (en) 2009-12-03 2011-06-09 Alcon Research, Ltd. Carboxyvinyl polymer-containing nanoparticle suspension
US9532222B2 (en) 2010-03-03 2016-12-27 Duo Security, Inc. System and method of notifying mobile devices to complete transactions after additional agent verification
US9544143B2 (en) 2010-03-03 2017-01-10 Duo Security, Inc. System and method of notifying mobile devices to complete transactions
US9467463B2 (en) 2011-09-02 2016-10-11 Duo Security, Inc. System and method for assessing vulnerability of a mobile device
AU2012351948A1 (en) * 2011-12-16 2014-07-10 Allergan, Inc. Ophthalmic compositions comprising polyvinyl capralactam - polyvinyl acetate - polyethylene glycol graft copolymer
EP3013790A1 (en) 2013-06-27 2016-05-04 Mylan Laboratories Ltd. Process for the preparation of nepafenac
EP3470059B1 (en) 2015-01-26 2020-04-01 Bausch & Lomb Incorporated Ophthalmic suspension composition
US9930060B2 (en) 2015-06-01 2018-03-27 Duo Security, Inc. Method for enforcing endpoint health standards
US10412113B2 (en) 2017-12-08 2019-09-10 Duo Security, Inc. Systems and methods for intelligently configuring computer security
US11658962B2 (en) 2018-12-07 2023-05-23 Cisco Technology, Inc. Systems and methods of push-based verification of a transaction
CN114272207B (zh) * 2022-01-21 2023-04-11 山东诺明康药物研究院有限公司 一种纳米晶混悬滴眼液及其制备方法

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1226344A (zh) 1967-07-31 1971-03-24
SE400966B (sv) 1975-08-13 1978-04-17 Robins Co Inc A H Forfarande for framstellning av 2-amino-3-(eller 5-)bensoyl-fenylettiksyror
US4313949A (en) 1979-09-26 1982-02-02 A. H. Robins Company, Inc. Method of producing an inhibitory effect on blood platelet aggregation
US4254146A (en) 1979-10-18 1981-03-03 A. H. Robins Company, Inc. 3-Benzoyl-2-nitrophenylacetic acids, metal salts, amides and esters
IL61945A (en) 1980-02-19 1984-09-30 Robins Co Inc A H 2-amino-3-(hydroxy(phenyl)methyl)phenylacetic acids,esters and amides and pharmaceutical compositions containing them
US4503073A (en) 1981-01-07 1985-03-05 A. H. Robins Company, Incorporated 2-Amino-3-(alkylthiobenzoyl)-phenylacetic acids
IL64724A0 (en) 1981-02-17 1982-03-31 Robins Co Inc A H 2-amino-3-(halobenzoyl)-methylphenylacetic acids and esters and salts thereof and pharmaceutical compositions containing them
US4568695A (en) 1983-12-07 1986-02-04 A. H. Robins Company, Incorporated 2-Amino-3-benzoyl-phenethylalcohols and intermediates therefor
DE3668450D1 (de) 1985-03-14 1990-03-01 Smithkline Dauelsberg 5-aminosalicylsaeurederivate von nicht-steroidalen entzuendungshemmenden sauren.
US4851443A (en) 1985-03-14 1989-07-25 Smith Kline Dauelsberg, Gmbh Carboxylic acid amides, compositions and medical use thereof
US4683242A (en) 1985-10-28 1987-07-28 A. H. Robins Company, Incorporated Transdermal treatment for pain and inflammation with 2-amino-3-aroylbenzeneacetic acids, salts and esters
DK406686D0 (da) 1986-08-26 1986-08-26 Hans Bundgaard Carboxylsyrederivater
US4910225A (en) 1988-01-27 1990-03-20 Senju Pharmaceutical Co., Ltd. Locally administrable therapeutic composition for inflammatory disease
US5461081A (en) 1989-09-28 1995-10-24 Alcon Laboratories, Inc. Topical ophthalmic pharmaceutical vehicles
US5521222A (en) 1989-09-28 1996-05-28 Alcon Laboratories, Inc. Topical ophthalmic pharmaceutical vehicles
US5624893A (en) 1993-10-14 1997-04-29 Alcon Laboratories, Inc. Pharmaceutical compositions and methods of treatment of the cornea following laser irradiation
US5475034A (en) 1994-06-06 1995-12-12 Alcon Laboratories, Inc. Topically administrable compositions containing 3-benzoylphenylacetic acid derivatives for treatment of ophthalmic inflammatory disorders
US6066671A (en) * 1997-12-19 2000-05-23 Alcon Laboratories, Inc. Treatment of GLC1A glaucoma with 3-benzoyl-phenylacetic acids, esters, or amides
AR030346A1 (es) 2000-08-14 2003-08-20 Alcon Inc Metodo de tratamiento de desordenes neurodegenerativos de la retina y cabeza de nervio optico
AR030345A1 (es) * 2000-08-14 2003-08-20 Alcon Inc Metodo de tratamiento de desordenes relacionados con angiogenesis
JP2005525408A (ja) 2002-05-03 2005-08-25 アルコン，インコーポレイテッド アンフェナクまたはネパフェナクを用いる血管内皮増殖因子媒介性血管障害の処置方法
JP4500261B2 (ja) 2003-01-21 2010-07-14 千寿製薬株式会社 ２−アミノ−３−（４−ブロモベンゾイル）フェニル酢酸含有水性液剤
TWI358290B (en) 2004-12-02 2012-02-21 Alcon Inc Topical nepafenac formulations

Cited By (5)

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Publication number Priority date Publication date Assignee Title
CN104490861A (zh) * 2014-11-21 2015-04-08 三明欣茂药业有限公司 一种缓释型奈帕芬胺眼用制剂
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CN106963730A (zh) * 2016-12-22 2017-07-21 广州仁恒医药科技股份有限公司 高度稳定的奈帕芬胺眼用药物组合物
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