CN1311670A - 胆碱能试剂在治疗老花眼中的应用 - Google Patents
胆碱能试剂在治疗老花眼中的应用 Download PDFInfo
- Publication number
- CN1311670A CN1311670A CN99809051A CN99809051A CN1311670A CN 1311670 A CN1311670 A CN 1311670A CN 99809051 A CN99809051 A CN 99809051A CN 99809051 A CN99809051 A CN 99809051A CN 1311670 A CN1311670 A CN 1311670A
- Authority
- CN
- China
- Prior art keywords
- muscarine
- antagonist
- described method
- eyes
- receptor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/695—Silicon compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/221—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/452—Piperidinium derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Ophthalmology & Optometry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
公开了增加或减少副交感/胆碱能/睫状体紧张性收缩以恢复眼睛的静止位置并允许正常的正性调节和负性调节的方法,所述方法包括,向老花眼患者施用有效量的毒蕈硷药物。
Description
老花眼在中年后发生,是指眼睛不能正确地聚焦。这种与年龄有关的眼疾病的表现形式是丧失了调节能力。调节能力是眼睛通过改变晶状体的形状使其变得更接近球状或凸面而通过晶状体聚焦在近或远的物体上的能力。
睫状肌通过称为小带的悬韧带控制晶状体的形状。与大多数平滑肌一样,睫状肌受双重神经支配,它同时接受交感神经和副交感神经纤维。
在睫状肌中,调节所需的收缩受副交感神经或胆碱能的控制。虽然副交感神经控制是主要的,但交感神经或肾上腺能的神经支配对抗胆碱能的控制并在睫状肌的松弛中起次要作用。
目前对调节的最常见的理论是假设调节的生理性休息的情况是发生在当正视眼聚焦在远处的目标上时,需要良好的分辨率。定位该远处目标的视觉值的事实可以称为眼的零屈光度已倾向于保持活性调节对近物体单向的概念。
但是,如果考虑对调节的正常刺激其本质是视觉的,则眼的休息状态必需通过移走所有的视觉刺激来确定,例如,在完全的黑暗中或在光照但完全没有视野的情况下。这种眼睛的休息状态被称为“紧张调节”、“宇宙近视”和“天空近视”,在极低照明或完全黑暗下平均值约为1D但可以高达2D近视。
这暗示调节的休息状态存在于当眼睛聚焦于约1米远的物体时。因此,远处的物体将通过活性负性调节聚焦在视网膜上,近处的物体将通过活性正性调节聚焦。
因此,在眼睛的自然休息状态,副交感/胆碱能系统保持睫状肌紧张,即,睫状肌收缩并且小带张力松弛,从而使晶状体更接近于球形并处于正向位置以增加眼睛的屈光能力。因此,眼睛在自然情况下是处于“紧张调节”状态,适宜的刺激可以进一步激活正性调节以及激活负性调节。
发明概述
根据本发明的方法,提供了增加或减少副交感/胆碱能/睫状体紧张性收缩以恢复眼睛的静止位置并允许正常的正性调节和负性调节。这种在副交感神经调节下的睫状肌作用可以引起小带的松弛,从而使晶状体能够更接近球性。
本发明的具体方法包括向老花眼患者给药有效量的毒蕈硷激动剂或拮抗剂。
激动剂/拮抗剂以可药用的眼用制剂给药,优选通过将制剂以无刺激的无菌溶液或混悬液的形式涂抹在眼睛上将激动剂进行局部给药。就此而言,制剂的pH优选与眼相容。更具体地讲,根据本发明,可以选择毒蕈硷试剂以作用于各种睫状肌的M受体。发明详述
虽然不想将本发明的治疗限制于所提出的作用机制上,但确信睫状肌的环形纤维的作用会引起小带的松弛并允许晶状体有更大的弯曲或球状。睫状肌的放射状/纵向纤维的松弛或伸长使得晶状体可以向前移动。但是,由于晶状体在整个生命过程中连续生长,其增加的体积以及弹性的丧失超出了睫状肌进行适宜的调节改变的能力。此外,预测眼睛的休息状态也发生了改变。
此外,对大脑的衰老研究已经证实了由于神经递质乙酰胆碱的减少所引起的胆碱能系统的功能丧失。这可能是由于胆碱乙酰转移酶(CHAT)或乙酰胆碱合成酶生产的减少,因为胆碱能受体细胞不会随着年龄而减少。也就是说,睫状肌具有相同数量的受体并且肌肉的收缩能力年龄在年轻和年老的个体中是相同的。
根据本发明,毒蕈硷受体亚型使得睫状肌的环状或纵向纤维可以通过对M1-M5受体的作用而选择性地收缩或松弛。
表1中给出了受体亚型的简要描述。
表1
受体亚型 组织或细胞功能 信号传导机制
M1 收缩或分泌 PI,Ca
M2 松弛 CAMP
M3 收缩或分泌 PI,Ca
M4 松弛 CAMP
M5 收缩或分泌 PI,Ca
其中
PI 磷酸肌醇水解(刺激应答)
Ca 细胞内的游离钙增加(刺激应答)
cAMP环磷酸腺苷(AMP)形成的增加(抑制应答)
M3受体亚型最为常见,其主要见于环状纤维,M5受体主要位于纵向纤维内。因此,M5受体的抑制和/或交感神经系统的刺激可以允许纵向纤维的松弛/伸长。
用于实践本发明的化合物可以是任何毒蕈硷激动剂或拮抗剂。本文所用的术语“毒蕈硷激动剂”是指任何能够在自主的神经-效果接点产生净的抗交感神经应答的化合物。可以阻断副交感神经系统的副交感阻滞剂是毒蕈硷拮抗剂,可以刺激副交感神经系统的拟副交感剂是毒蕈硷激动剂。如果能被毒蕈硷激动剂如乙酰胆碱激活,则神经-效果接点被认为是胆碱能的。
以下是可用于本发明的代表性的毒蕈硷激动剂和拮抗剂的列表,但它们并不是将本发明限于所列的特定的组和化合物。毒蕈硷激动剂
通常,毒蕈硷激动剂是M非选择性的并且是拟副交感剂,它刺激副交感神经系统。所述毒蕈硷激动剂包括但不仅限于:
毛果芸香碱
异毛果芸香碱内酰胺
卡巴胆碱
氨基甲酰甲基胆硷
乙酰甲胆硷
毒蕈硷毒蕈硷拮抗剂
毒蕈硷拮抗剂是副交感神经阻滞药并可阻断副交感神经系统。
这些拮抗剂对指定的受体具有很高的亲和性,但它们也可与其它受体亚型以较低的亲和性结合。所述毒蕈硷拮抗剂包括但不仅限于(涉及M受体):
M1哌仑西平、替伦折平,(M1/M4)三己芬迪
M2(+)(11-({2-[(二乙基氨基甲基]-1-哌啶基}乙酰基)-5,11-二氢-6H-吡啶并(2,3-b)(1,4)苯并二氮杂-6-酮;
(+)5,11-二氢-11-({2-[(二丙基氨基)甲基]-1-哌啶基)氨基]羰基}-6H-吡啶并(2,3-b)(1,4)苯并二氮杂-6-酮;喜巴辛、Triptiramine
M3二苯基乙酰氧基-N-甲基哌啶甲碘化物、(+)对-氟-六氢-硅杂-二苯哌丁醇盐酸盐
M4哌仑西平、替伦折平
具有毒蕈硷激动剂功能的上述化合物的类似物也包括在本发明的范围内。所述类似物恢复眼睛的静止位置以及允许正常的正性和负性调节的能力可以很容易地通过常规的实验进行测试。
本发明的方法特别适用于没有需要用毒蕈硷激动剂进行眼科治疗的适应症的患者。
本发明的毒蕈硷激动剂可以直接给药,或者以可药用盐的形式给药。当用于制剂中时,毒蕈硷激动剂的盐必需既是药理学可接受的又是制药学可接受的,但不可药用盐可用于制备活性的游离化合物或其可药用盐。
许多本发明的化合物的性质是本领域已知的,并且已知在其常规的使用条件下是安全的。因此,本发明的治疗方法可以以与已知的眼科疗法一致的常规的方式进行,并同时避免特殊应用方法带来的刺激和不适。
本发明的制剂可以包括任何能够将本发明的化合物传递到眼的制剂。优选将本发明的毒蕈硷激动剂以局部制剂应用于眼。局部制剂是指适于应用于眼睛表面的制剂。在所述制剂中,制剂中的治疗化合物与眼睛表面接触并穿透到眼组织的深处。所述制剂通常含有液体载体,所述液体载体可以是含水溶液或混悬液。
优选将本发明的毒蕈硷激动剂以可以延长毒蕈硷激动剂对神经-效果接点的活性持续时间的制剂形式提供。因此,所述制剂可以含有以上所述的任何毒蕈硷激动剂和拮抗剂。
本发明的化合物可以以可药用眼科制剂、即可以产生医学上有利的治疗效果而不会同时引起临床上显著的副作用的制剂形式应用。临床上显著的作用是指制剂的不可接受的副作用,包括医学和美容上可接受的作用。不可接受的副作用的例子包括使眼睛变红或刺激眼睛,损伤远距离视力、升高眼内压或眶上部神经痛。
关于毛果芸香硷,本发明所用的剂量低于可以引起所述副反应的剂量。
本发明的化合物以治疗有效量给药。治疗有效量是可以使眼睛的静止位置恢复以及允许正常的正性和负性调节的剂量。通常将化合物以整个制剂重量的约0.001%至约4%的浓度加入到本发明的眼科制剂中。
优选将本发明的化合物局部给药并以医学可接受的、基本无菌的无刺激性眼科制剂的形式给药。眼科制剂通常可以含有药物可接受浓度的盐、缓冲剂、防腐剂、粘度调节剂、渗透压调节剂和传递促进剂。
可以使用的盐包括但不仅限于氯化钠、硫酸锌和氯化钾。可以使用的缓冲剂包括但不仅限于硼酸和柠檬酸。可以使用的防腐剂包括但不仅限于氯苄烷铵和乙二胺四乙酸二钠。可以使用的粘度调节剂包括但不仅限于甲基纤维素、甘油和聚乙二醇。可以使用的渗透压调节剂包括但不仅限于甘露醇和山梨醇。可以促进本发明的治疗化合物传递到水状液中的传递促进剂包括可以增加角膜通透性的物质,例如表面活性剂、湿润剂、脂质体、DMSO等。湿润剂是可以通过温和地破坏外层角膜表面而增加角膜通透性的物质。优选的湿润剂是氯苄烷铵。湿润剂的其它例子包括山梨醇酯和聚氧乙烯醚。
应当理解,虽然给出了具体的制剂,但仍可以进行各种改变。任何情况下,用于眼睛的眼科制剂均应是无刺激性的并且对眼睛没有损伤,而且还可以有效地提供所需的结果。通常,所述制剂可以在液体载体中应用并且优选含水载体,但在某些情况下,也可以将速溶形式的药物以粉末的形式给药或从各种类型的涂药器中涂抹到眼睛内。也可以使用眼喷雾、滴眼液和其它涂抹方法。
剂量水平根据所治疗的个体以及所用的具体药物可以有很大改变。适宜的剂量很容易根据本领域普通技术人员熟知的方法确定。
人类有一个平均的调节幅度(以屈光度来衡量),该调节幅度随着年龄的增长而稳定地下降。本发明的方法可用于最大屈光能力在10或10以下的患者,优选最大屈光能力在6或6以下的患者,首选最大屈光能力在4或4以下的患者。
优选将制剂以无菌溶液的形式包装在市场上常见的滴瓶中。也可使用其它容器,包括眼药杯(eye cup)。优选将制剂与使用该制剂治疗老花眼的说明一起包装,所述说明通常指导给药者向每个眼中滴1至2滴溶液。
在本发明的具体实施例中,可以配制如下的基础溶液:氯化钠0.3%;乙二胺四乙酸二钠0.1%;硼酸1.0%;氯苄烷铵0.01%;氢氧化钠(调至pH6.4)和水。向该基础溶液中加入浓度为0.1%重量/体积的毛果芸香硷。
将上述制剂向患有老花眼(表现为阅读时不适或者不能阅读细小的字体)的50岁的老人的眼睛给药。在给药该眼药水后视力得到改善。
当用其它毒蕈硷激动剂代替毛果芸香硷时,得到了相似的结果。
尽管以上为了说明本发明的优选使用方式而描述了本发明的具体方法,但应当理解本发明并不仅限于此。因此,本领域技术人员可以进行的各种修饰、改变或等同的排列均应当认为是在所附权利要求所定义的本发明的范围内。
Claims (13)
1、增加或减少副交感/胆碱能/睫状体紧张性收缩以恢复眼睛的静止位置并允许正常的正性调节和负性调节的方法,所述方法包括,向老花眼患者施用有效量的毒蕈硷激动剂。
2、权利要求1所述的方法,其中的毒蕈硷激动剂以可药用眼科制剂的形式对眼睛局部给药。
3、权利要求2的方法,其中的毒蕈硷激动剂选自毛果芸香碱、异毛果芸香碱内酰胺、卡巴胆碱、氨基甲酰甲基胆硷、乙酰甲胆硷和毒蕈硷。
4、增加或减少副交感/胆碱能/睫状体紧张性收缩以恢复眼睛的静止位置并允许正常的正性调节和负性调节的方法,所述方法包括,向老花眼患者施用有效量的毒蕈硷拮抗剂。
5、权利要求4所述的方法,其中的毒蕈硷拮抗剂以可药用眼科制剂的形式对眼睛局部给药。
6、权利要求5所述的方法,其中的毒蕈硷拮抗剂选自作用于睫状肌M1受体的拮抗剂。
7、权利要求6所述的方法,其中的毒蕈硷拮抗剂选自哌仑西平、替伦折平和(M1/M4)三己芬迪。
8、权利要求5所述的方法,其中的毒蕈硷拮抗剂选自作用于睫状肌M2受体的拮抗剂。
9、权利要求8所述的方法,其中的毒蕈硷拮抗剂选自(+)(11-({2-[(二乙基氨基甲基]-1-哌啶基}乙酰基)-5,11-二氢-6H-吡啶并(2,3-b)(1,4)苯并二氮杂-6-酮和
(+)5,11-二氢-11-{[(2-[二丙基氨基)甲基]-1-哌啶基)氨基]羰基}-6H-吡啶并(2,3-b)(1,4)苯并二氮杂-6-酮。
10、权利要求5所述的方法,其中的毒蕈硷拮抗剂选自作用于睫状肌M3受体的拮抗剂。
11、权利要求10所述的方法,其中的毒蕈硷拮抗剂选自二苯基乙酰氧基-N-甲基哌啶甲碘化物和(+)对-氟-六氢-硅杂-二苯哌丁醇盐酸盐。
12、权利要求5所述的方法,其中的毒蕈硷拮抗剂选自作用于睫状肌M4受体的拮抗剂。
13、权利要求12所述的方法,其中的毒蕈硷拮抗剂选自哌仑西平、替伦折平。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/126064 | 1998-07-30 | ||
US09/126,064 US6291466B1 (en) | 1998-07-30 | 1998-07-30 | Cholinergic agents in the treatment of presbyopia |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1311670A true CN1311670A (zh) | 2001-09-05 |
CN1157186C CN1157186C (zh) | 2004-07-14 |
Family
ID=22422802
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998090514A Expired - Fee Related CN1157186C (zh) | 1998-07-30 | 1999-07-22 | 胆碱能试剂在治疗老花眼中的应用 |
Country Status (13)
Country | Link |
---|---|
US (2) | US6291466B1 (zh) |
EP (1) | EP1100480B1 (zh) |
JP (1) | JP2002521429A (zh) |
KR (1) | KR20010079593A (zh) |
CN (1) | CN1157186C (zh) |
AT (1) | ATE250412T1 (zh) |
AU (1) | AU754588B2 (zh) |
BR (1) | BR9912599A (zh) |
CA (1) | CA2339093A1 (zh) |
DE (1) | DE69911620T2 (zh) |
ES (1) | ES2207963T3 (zh) |
HK (1) | HK1035493A1 (zh) |
WO (1) | WO2000006135A2 (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108601768A (zh) * | 2015-12-29 | 2018-09-28 | R·皮内利 | 用于治疗老花眼的组合物 |
CN110496215A (zh) * | 2019-08-23 | 2019-11-26 | 中国人民解放军总医院 | 一种治疗老视的水性滴眼液及其制备方法 |
CN112272558A (zh) * | 2018-04-24 | 2021-01-26 | 阿勒根公司 | 盐酸毛果芸香碱用于治疗眼部病症的用途 |
CN114630669A (zh) * | 2020-10-14 | 2022-06-14 | 参天制药株式会社 | 稳定的医药组合物 |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2658158C (en) | 2006-07-11 | 2014-10-21 | Refocus Group, Inc. | Scleral prosthesis for treating presbyopia and other eye disorders and related devices and methods |
US8911496B2 (en) | 2006-07-11 | 2014-12-16 | Refocus Group, Inc. | Scleral prosthesis for treating presbyopia and other eye disorders and related devices and methods |
ATE439863T1 (de) * | 2006-12-18 | 2009-09-15 | Jorge Luis Benozzi | Ophthalmische zusammensetzungen von parasympathischen stimulantia und entzündungshemmer zur verwendung bei der behandlung von presbyopie |
GB0711151D0 (en) * | 2007-06-11 | 2007-07-18 | Sra Dev Ltd | Switch for use with an ultrasonic surgical tool |
GB0724558D0 (en) * | 2007-12-15 | 2008-01-30 | Sharma Anant | Optical correction |
US8299079B2 (en) * | 2009-05-22 | 2012-10-30 | Kaufman Herbert E | Preparations and methods for ameliorating or reducing presbyopia |
WO2010135731A1 (en) * | 2009-05-22 | 2010-11-25 | Kaufman Herbert E | Preparations and methods for ameliorating or reducing presbyopia |
EP2512492A1 (en) * | 2009-12-14 | 2012-10-24 | University of Massachusetts | Methods of inhibiting cataracts and presbyopia |
JP2014510022A (ja) * | 2011-04-07 | 2014-04-24 | スキャンポ・アーゲー | 眼精疲労の処置方法 |
RU2630968C2 (ru) | 2011-09-20 | 2017-09-15 | Аллерган, Инк. | Лекарственные средства и способы лечения пресбиопии, умеренной гиперметропии и неправильного астигматизма |
CA2904657C (en) | 2013-03-14 | 2021-02-16 | The University Of Massachusetts | Methods of inhibiting cataracts and presbyopia |
US10307408B2 (en) | 2013-08-28 | 2019-06-04 | Presbyopia Therapies, LLC | Contact lens compositions and methods for the treatment of presbyopia |
US9844537B2 (en) | 2013-08-28 | 2017-12-19 | Presbyopia Therapies Llc | Compositions and methods for the treatment of presbyopia |
US10064818B2 (en) | 2013-08-28 | 2018-09-04 | Presbyopia Therapies, LLC | Compositions and methods for the treatment of presbyopia |
US9089562B2 (en) * | 2013-08-28 | 2015-07-28 | Presbyopia Therapies Llc | Compositions and methods for the treatment of presbyopia |
US9833441B2 (en) | 2013-08-28 | 2017-12-05 | Presbyopia Therapies Llc | Compositions and methods for the treatment of presbyopia |
US9320709B2 (en) | 2013-08-28 | 2016-04-26 | Presbyopia Therapies Llc | Storage stable compositions and methods for the treatment of refractive errors of the eye |
US9968594B2 (en) | 2013-08-28 | 2018-05-15 | Presbyopia Therapies Llc | Compositions and methods for the treatment of presbyopia |
US9314427B2 (en) | 2013-08-28 | 2016-04-19 | Presbyopia Therapies Llc | Compositions and methods for the improvement of distance vision and the treatment of refractive errors of the eye |
US10617763B2 (en) | 2013-08-28 | 2020-04-14 | Presbyopia Therapies, LLC | Compositions and methods for the treatment of presbyopia |
US11179327B2 (en) | 2013-08-28 | 2021-11-23 | Lenz Therapeutics, Inc. | Compositions and methods for the treatment of presbyopia |
WO2015122853A1 (en) * | 2014-02-11 | 2015-08-20 | Vid D.O.O. | Pharmacological ophthalmic composition for use in the correction of presbyopia and its administration |
EP3310336A4 (en) | 2015-06-18 | 2018-12-05 | Presbyopia Therapies, LLC | Storage stable compositions and methods for the treatment of refractive errors of the eye |
US10736863B2 (en) | 2015-11-13 | 2020-08-11 | University Of Massachusetts | Methods of inhibiting cataracts and presbyopia |
CN116726006A (zh) | 2016-08-19 | 2023-09-12 | 阿拉西斯医药公司 | 眼科药物组合物及其相关用途 |
CN111372576A (zh) * | 2017-11-17 | 2020-07-03 | 塞尔利克斯生物私人有限公司 | 用于治疗眼部病症的组合物和方法 |
WO2020072971A1 (en) * | 2018-10-06 | 2020-04-09 | Biotheravision Llc | Ophthalmic preparations of muscarinic agonist and methods of use |
BR112022026911A2 (pt) * | 2020-09-11 | 2023-03-28 | Intratus Nevada Inc | Composições e métodos para tratar presbiopia, hipermetropia, astigmatismo, diminuição da estereopsia e diminuição da sensibilidade ao contraste |
US11648247B1 (en) | 2021-12-16 | 2023-05-16 | Lenz Therapeutics, Inc. | Compositions and methods for the treatment of presbyopia |
US11857538B2 (en) | 2022-01-14 | 2024-01-02 | Somerset Therapeutics, Llc | Stable pilocarpine formulations with modified buffer characteristics and related methods |
US11857539B2 (en) | 2022-02-09 | 2024-01-02 | Somerset Therapeutics, Llc | Gel ophthalmic formulations of pilocarpine and brimonidine compounds and related methods |
WO2023190653A1 (ja) * | 2022-03-30 | 2023-10-05 | 参天製薬株式会社 | 医薬製剤の滅菌法と包装体 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5166317A (en) * | 1988-10-31 | 1992-11-24 | Houston Biotechnology Incorporated | Neurotrophic factor |
FR2638970A1 (fr) | 1988-11-16 | 1990-05-18 | Corbiere Jerome | Nouvelles compositions pharmaceutiques agissant sur la presbytie et leur procede d'obtention |
US5122522A (en) * | 1989-06-21 | 1992-06-16 | The Trustees Of The University Of Pennsylvania | Treatment and control of ocular development |
WO1990015604A1 (en) | 1989-06-21 | 1990-12-27 | The Trustees Of The University Of Pennsylvania | Treatment and control of ocular development |
AU4653993A (en) | 1992-07-02 | 1994-01-31 | Telor Ophthalmic Pharmaceuticals, Inc. | Methods and products for treating presbyopia |
-
1998
- 1998-07-30 US US09/126,064 patent/US6291466B1/en not_active Expired - Lifetime
-
1999
- 1999-07-22 DE DE69911620T patent/DE69911620T2/de not_active Expired - Fee Related
- 1999-07-22 CA CA002339093A patent/CA2339093A1/en not_active Abandoned
- 1999-07-22 AU AU52160/99A patent/AU754588B2/en not_active Ceased
- 1999-07-22 KR KR1020017001311A patent/KR20010079593A/ko not_active Application Discontinuation
- 1999-07-22 AT AT99937295T patent/ATE250412T1/de not_active IP Right Cessation
- 1999-07-22 WO PCT/US1999/016260 patent/WO2000006135A2/en not_active Application Discontinuation
- 1999-07-22 EP EP99937295A patent/EP1100480B1/en not_active Expired - Lifetime
- 1999-07-22 BR BR9912599-4A patent/BR9912599A/pt not_active IP Right Cessation
- 1999-07-22 ES ES99937295T patent/ES2207963T3/es not_active Expired - Lifetime
- 1999-07-22 JP JP2000561990A patent/JP2002521429A/ja active Pending
- 1999-07-22 CN CNB998090514A patent/CN1157186C/zh not_active Expired - Fee Related
-
2001
- 2001-04-25 US US09/842,299 patent/US6410544B1/en not_active Expired - Lifetime
- 2001-08-31 HK HK01106162A patent/HK1035493A1/xx not_active IP Right Cessation
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108601768A (zh) * | 2015-12-29 | 2018-09-28 | R·皮内利 | 用于治疗老花眼的组合物 |
CN112272558A (zh) * | 2018-04-24 | 2021-01-26 | 阿勒根公司 | 盐酸毛果芸香碱用于治疗眼部病症的用途 |
US11285134B2 (en) | 2018-04-24 | 2022-03-29 | Allergan, Inc. | Presbyopia treatments |
CN110496215A (zh) * | 2019-08-23 | 2019-11-26 | 中国人民解放军总医院 | 一种治疗老视的水性滴眼液及其制备方法 |
CN114630669A (zh) * | 2020-10-14 | 2022-06-14 | 参天制药株式会社 | 稳定的医药组合物 |
CN114630669B (zh) * | 2020-10-14 | 2023-03-24 | 参天制药株式会社 | 稳定的医药组合物 |
Also Published As
Publication number | Publication date |
---|---|
ES2207963T3 (es) | 2004-06-01 |
HK1035493A1 (en) | 2001-11-30 |
US6291466B1 (en) | 2001-09-18 |
WO2000006135A2 (en) | 2000-02-10 |
US6410544B1 (en) | 2002-06-25 |
DE69911620D1 (de) | 2003-10-30 |
BR9912599A (pt) | 2001-05-02 |
KR20010079593A (ko) | 2001-08-22 |
ATE250412T1 (de) | 2003-10-15 |
EP1100480A2 (en) | 2001-05-23 |
EP1100480B1 (en) | 2003-09-24 |
AU5216099A (en) | 2000-02-21 |
JP2002521429A (ja) | 2002-07-16 |
AU754588B2 (en) | 2002-11-21 |
DE69911620T2 (de) | 2004-07-29 |
CA2339093A1 (en) | 2000-02-10 |
CN1157186C (zh) | 2004-07-14 |
WO2000006135A3 (en) | 2000-03-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1157186C (zh) | 胆碱能试剂在治疗老花眼中的应用 | |
US5459133A (en) | Methods and products for treating presbyopia | |
CA2360685C (en) | Methods for restoring and/or enhancing accommodation in pseudo phakia | |
US6273092B1 (en) | Methods for treating various eye disorders | |
KR20140076587A (ko) | 노안, 경도 원시 및 불규칙한 난시의 치료를 위한 조성물 및 방법 | |
EP3505169A1 (en) | Medicament comprising pilocarpine and thymoxamine | |
CN113226300A (zh) | 治疗老花眼的组合物和方法 | |
EP2770979B1 (en) | Improved cross-linking composition delivered by iontophoresis, useful for the treatment of keratoconus | |
JP2022536662A (ja) | 多焦点性を作り出すために偽水晶体患者において副交感神経刺激薬を単独でまたは1種類もしくは複数種類のαアゴニストと組み合わせて使用する方法 | |
JP2020527609A (ja) | 近視の処置のための組成物および方法 | |
JP2022541854A (ja) | 老視の治療のための組成物および方法 | |
CN114588156A (zh) | 一种眼用制剂及其在治疗老花眼中的应用 | |
US20170007637A1 (en) | Pharmacological ophthalmic composition for use in the correction of presbyopia and its administration | |
Karanfil et al. | Update on presbyopia-correcting drops | |
MXPA01000803A (en) | Cholinergic agents in the treatment of presbyopia | |
CN1206987C (zh) | 吲哚美辛脂质体滴眼液 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
ASS | Succession or assignment of patent right |
Owner name: ALLERGAN INC. Free format text: FORMER OWNER: ALLERGAN SALES, INC. Effective date: 20030925 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20030925 Address after: American California Applicant after: Allergan Address before: American California Applicant before: Allergan Sales, INC. |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |