CN1638734A - 微粒结膜下给药的药物释放*** - Google Patents
微粒结膜下给药的药物释放*** Download PDFInfo
- Publication number
- CN1638734A CN1638734A CNA038044064A CN03804406A CN1638734A CN 1638734 A CN1638734 A CN 1638734A CN A038044064 A CNA038044064 A CN A038044064A CN 03804406 A CN03804406 A CN 03804406A CN 1638734 A CN1638734 A CN 1638734A
- Authority
- CN
- China
- Prior art keywords
- microgranule
- rear portion
- delivery system
- medicine
- drug delivery
- 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.)
- Pending
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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Virology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明提供了一种良好的眼球后部药物释放***。本发明的注射剂含有含药物的微粒,是药物能向眼球后部转移的结膜下注射剂。将含药的微粒结膜下给药时,对眼组织的伤害少且能使药物高效率地输送到眼球后部(视网膜、脉络膜、视神经等)。微粒优选由合成生物可降解性高分子制成,平均粒径为50nm~150μm,药物在微粒中均匀分散。优选的药物为抗炎剂、免疫抑制剂、抗病毒剂、抗癌剂、血管新生抑制剂、视神经保护剂、抗菌剂或抗真菌剂。
Description
技术领域
本发明涉及用于视网膜、脉络膜、视神经等眼球后部的药物释放***。
背景技术
在视网膜、脉络膜、视神经等眼球后部的疾病中,难治性疾病很多,目前迫切希望开发出有效的治疗方法。对于眼部疾病,最常见的是点眼给药治疗,但药物基本上不向视网膜、脉络膜、视神经等眼球后部转移,而且,就算转移也非常难于使药物浓度得以维持。
所以,对于眼球后部疾病的给药方法,已经尝试了静脉注射、口服给药、玻璃体注射。静脉注射或口服给药时,药物向靶部位的转移量极其微小,而且显著地表现出了所不希望的药物全身作用(副作用)。
玻璃体注射是将药物直接注入眼内,因此其向眼球后部的药物转移量比静脉注射或口服给药多。关于玻璃体注射的眼球后部释放,眼科药学与治疗学杂志 (Journal of Ocular Pharmacology andtherapeutics),(2001)17/4,393-401中已有综述。但是玻璃体注射是需要高度技术的给药方法,由于伴随有相当的痛苦,患者的负担也很大,多次给药非常困难。
相对于这些给药方法,结膜下注射的手法较简单,比玻璃体给药对眼部的伤害小且患者的负担小。结膜下注射后的药物向眼球后部的转移性已有报告(Invest.Ophthalmol.Visual Sci.18(3)250-255,1979)、其半衰期很短,很难长时间维持药物在组织中的浓度。因此,为了维持药物在组织中的浓度必须频繁多次给药,但频繁多次给药使患者的负担加大。
为了避免频繁多次给药,作为维持眼内药物浓度的方法,已知的有静脉注射药物-高分子结合体的方法(Invest.Ophthalmol.VisualSci.40(1),2690-2696,1999)或在玻璃体中注射含有药物的微球的方法(特开2000-247871)等。
如上所述,现有的技术很难维持结膜下注射的药物在组织中的浓度,期待开发出结膜下注射的用于眼球后部的药物持续释放***。
发明内容
本发明者们经深入研究,结果发现,若将含药物的缓释性微粒结膜下给药,作为眼球后部的药物持续释放***非常有用。
本发明涉及将含药的微粒结膜下给药眼球后部药物释放***。本发明还涉及结膜下注射剂,其含有含药的微粒,且其中药物能向眼球后部转移。含药的微粒结膜下给药时,比静脉注射或口服给药的向眼球后部转移性好,对全身的副作用也小。而且比玻璃体注射手法简单,对患者的负担小。另外,由于使药物包含在微粒中,能长时间维持靶组织中的药物浓度。
在本发明中,形成微粒的材料优选生物可降解性高分子或生物可溶性高分子、作为具体例子可举出:聚乳酸、乳酸-乙醇酸共聚物、乳酸-己内酯共聚物、聚酐、聚原酸酯、聚ε-己内酯、聚丙烯氰基丙烯酸酯、多羟基链烷酸酯、聚磷酸酯、聚氨基酸、聚α羟基酸等生物可降解性高分子;明胶、骨胶原、透明质酸、葡聚糖、淀粉、藻酸钠、琼脂、支链淀粉、白蛋白、鹿角菜胶、果胶、黄原胶、茱萸烷胶(gellan gum)、酪蛋白、脱乙酰壳多糖、血纤维蛋白原等天然高分子;甲基丙烯酸共聚物、聚乙烯醇、羟丙基甲基纤维素、羟丙基甲基纤维素醋酸酯、羟乙基纤维素、羧甲基纤维素、甲基纤维素、聚乙烯吡咯烷酮、聚乙二醇、聚N-烷基丙烯酰胺等合成高分子。
这些高分子物质的分子量没有特别的限制,可根据微粒中所含药物的种类、药物的有效治疗浓度、药物释放时间等进行适当选择。
本发明的微粒的粒径优选50nm~150μm。粒径小于或等于50nm的微粒难以制造,粒径大于或等于150μm的微粒则粒径太大,不适于用于注射剂中。最优选的粒径为200nm~75μm。
本发明的药物释放***用于视网膜、脉络膜以及视神经疾病的治疗或者预防。作为具体疾病的例子可举出,各种原因引起的炎症、病毒或细菌的感染症、视网膜脉络膜的血管新生引发的疾病、视网膜缺血引发的疾病、白内障引发的视神经障碍。具体而言,可举出葡萄膜炎、巨细胞病毒视网膜炎、老年性黄斑变性、糖尿病性视网膜病变、增殖性玻璃体视网膜病变、视网膜剥离、视网膜色素变性、视网膜中央静脉阻塞、视网膜中央动脉阻塞等。
对于微粒中含有的药物没有特别的限制,可选择适合于对象疾病的药物。具体可举出,倍他米松、***、去炎松、强的松龙、氟甲龙、氢化可的松、***等类固醇药或其衍生物;溴芬那酸、双氯酚酸钠等抗炎剂;TNF-α抑制剂、PDE-IV抑制剂、ICE抑制剂等细胞因子抑制剂;环孢菌素、藤霉素等免疫抑制剂;甘环核苷、阿昔洛韦、β干扰素等抗病毒剂;氧氟沙星、克拉霉素、红霉素等的抗菌剂;氟苷、甲胺嘌呤、MPP抑制剂等的抗癌剂;血管内皮抑素、VEGF抑制剂、反义寡核苷酸、PKC抑制剂、粘合因子抑制剂、血管静止性类固醇等血管新生抑制剂;MK-801、噻马洛儿、肌酸、牛璜酸、BDNF等的神经保护剂/神经营养因子、乙酰唑胺等的碳酸脱水酶抑制剂;尿激酶等的血栓溶解剂。作为含药微粒,优选使药物在微粒中均匀分散的基质型或以药物为芯、以微粒囊化后得到的囊型。
微粒所含的药物量,可以根据药物的种类、有效治疗浓度、药物的释放时间、症状等进行适当增减。药物的含量为微粒的0.01~95重量%、优选为0.1~20重量%。
本发明的微粒可用以下的方法制造,但不限于这些方法。这些方法是使用公知研磨机的粉碎法、相分离法(凝聚法)、喷雾干燥法、超临界流体法、界面沉淀法、界面反应法。具体可以举出作为界面沉淀法的浸渍干燥法(J.Control.Release,2,343-352,(1985))、作为界面反应法的界面聚合法(Int.J.Pharm.,28,125-132(1986))、自乳化溶剂扩散法(J.Control.Release,25,89-98,(1993))等。根据微粒的粒径或所含药物的种类、性质或含量等,从这些制造方法中,适当地选择出合适的制造方法即可。
作为微粒的具体制造例,后述的实施例例示了以抗炎剂倍他米松作为药物,用聚乳酸作为微粒材料的含药微粒的制造例。
本发明的效果在后述的视网膜脉络膜药物浓度测定试验项中给予详细说明,用倍他米松作药物的例子,将含有倍他米松的微粒结膜下给药,测定脉络膜视网膜中的药物浓度时,发现脉络膜视网膜中的药物浓度得以持续保持。
本发明的药物释放***的微粒是结膜下给药。结膜下给药的方法可以是通常进行的结膜下注射。如背景技术部分所述,结膜下注射手法较简单且对患者的负担也小。
另外,运用本发明的***时,由于能高效率地将药物输送到靶部位的视网膜、脉络膜或视神经等眼球后部,因此能减少给药量,可望有减轻副作用的效果。
本发明的药物释放***使用的微粒是结膜下给药,所以优选注射剂作为给药剂型。注射剂运用常用的注射剂制剂化技术配制即可。例如,将通常用的添加剂,如氯化钠等渗透压调节剂、磷酸钠等缓冲剂、吐温80等表面活性剂、甲基纤维素等增粘剂等和微粒一起加入注射用蒸馏水中配制成制剂即可。另外,若用无针高压注射器时,则可以不用作成注射剂而直接以微粒的形式给药。
下文所示是微粒的制造例、制剂的配制例、药物浓度测定试验以及脉络膜血管新生抑制试验的结果。
具体实施方式
1、药微粒的制造方法
以下是能在本发明的药物释放***中使用的微粒的制造例。
将倍他米松(0.025g)和重均分子量为20000的聚乳酸(0.25g)溶解于苯甲醇(1.5ml)中,所得溶液作为药物/聚合物溶液。将2.0%(W/V)聚乙烯醇水溶液(30ml)在均化器中均化(5000rpm),向其中滴加药物/聚合物溶液。此混合物滴完后持续均化5分钟,配制成O/W型乳浊液。用搅拌器搅拌(300rpm)超纯水(300ml),向其中滴加配制好的O/W型乳浊液、滴完后持续搅拌1小时。搅拌完之后将所得到的悬浊液离心分离,除去上清液。为了洗净沉淀物,加入超纯水(30ml)使沉淀分散,再次离心分离除去上清液。此操作再重复一次。洗净的沉淀物过筛,得到粒径为50nm~75μm的粒子。将所得粒子冷冻干燥,即得到含有倍他米松的微球。
2、制剂的调制方法
使含有倍他米松的微球粉末(442mg)分散在4ml溶剂(0.4%(w/v)吐温80/2.6%(w/v)甘油水溶液)中,所得的分散液作为含倍他米松的微球注射剂。
3、脉络膜视网膜中药物浓度的测定试验
用含有倍他米松的微球注射剂,按下述方法测定脉络膜视网膜内的浓度。用倍他米松悬浊剂作为对照并按下述方法进行浓度测定。比较微球给药组和悬浊剂给药组的倍他米松在脉络膜视网膜内的浓度。倍他米松悬浊剂是将倍他米松悬浮分散在溶剂(0.4%(w/v)吐温80/2.6%(w/v)甘油水溶液)中所得的悬浊液。
1)将日本白色家兔两眼中点入盐酸奥布卡因(0.5%(W/V))点眼液进行眼表面麻醉。
2)用27G针的注射器,将含有倍他米松的微球注射剂在上部结膜下按每只眼睛100μL给药。微球中倍他米松的含量为4.6%(W/V),因此倍他米松的给药量约为500μg。对照组中,用27G针的注射器,将1%(W/V)的倍他米松悬浊剂在上部结膜下按每只眼睛50μL给药。
3)家兔给药后,分别在2、7、14、21、28天杀死,摘除眼球后,回收脉络膜视网膜、用高效液相色谱法测定脉络膜视网膜内倍他米松的浓度。
表1给出了药物的经时浓度变化结果。从表1可以明确看出,倍他米松悬浊剂的脉络膜视网膜内倍他米松浓度在7天后约为0.96μg/g组织,而14天后在检出限以下。与其相对,含有倍他米松微球注射剂的脉络膜视网膜内倍他米松浓度在28天后仍为0.09μg/g组织,脉络膜视网膜中药物浓度得以维持。
表1脉络膜视网膜内倍他米松浓度(μg/g组织)
对照组(悬浊剂) | 微球注射剂 | |
给药2天后 | 0.54±0.35 | 0.70±0.26 |
7天后 | 0.96±0.54 | 0.18 |
14天后 | 检出限以下 | 0.17±0.06 |
21天后 | 检出限以下 | 0.10±0.02 |
28天后 | 检出限以下 | 0.09±0.02 |
(表中脉络膜视网膜内倍他米松浓度表示的是3或4只眼的平均值±标准误差。微球注射剂的7天后的值由于4只眼中2只眼在检出限以下,所以表示的是2只眼的平均值。)
4、脉络膜血管新生的抑制试验
关于含有倍他米松的微球注射剂对脉络膜血管新生的抑制效果,用激光诱发的大鼠脉络膜血管新生模型,按如下方法进行探讨。用只含有溶剂(0.4%(w/v)吐温80/2.6%(w/v)甘油水溶液)的微球注射剂作为对照,进行如下的操作。
1)用5%(W/V)的盐酸***注射液和2%(W/V)盐酸赛拉嗪注射液的混合液(7∶1)按1ml/Kg对家兔肌肉注射,进行全身麻醉,在两眼点入0.5%(W/V)托品酰胺/0.5%(W/V)盐酸苯福林点眼液使其散瞳后,用氪激光凝固器进行光凝固。光凝固是在视网膜深层聚焦,避开大的血管,在各眼8处不同部位呈散在状进行,(凝固条件:光斑大小100μm、输出100mW、凝固时间0.1秒)。光凝固后,进行眼底照相,确认激光照射部位。
2)光凝固后接着用装有30G针的微量注射器,将含有倍他米松的微球注射剂在大鼠上部结膜下按每眼50μl给药,对照组中,将只含溶剂(0.4%(w/v)吐温80/2.6%(w/v)甘油水溶液的微球注射剂在上部结膜下按每眼50μl给药。
3)光凝固14天和28天后,尾静脉注射10%(w/v)的荧光素水溶液0.1ml,进行荧光眼底照相。通过荧光眼底照相确认没有漏出荧光的点被判定为阴性,确认有漏出荧光的点被判定为阳性。按照以下的计算公式,从对应于激光照射的8点阳性点数的比例,算出血管新生发生率。应予说明,显示出轻度漏荧光的点中每发生两个点计数为1个阳性。
血管新生发生率(%)=
(漏出荧光的点数/激光照射的点数)×100
所得结果用平均值±标准误差表示。用Studentt检验进行统计分析。两侧显著性水平为5%。
含有倍他米松微球的脉络膜血管新生的抑制效果由表2表示。相对于光凝固14天后对照组的血管新生发生率60.9±4.4%,含有倍他米松微球组的血管新生发生率为12.5±2.4%,表现出有统计学意义的脉络膜血管新生抑制作用。另外,相对于光凝固28天后对照组血管新生发生率73.4±6.0%,含有倍他米松的微球组的血管新生发生率为12.5±2.4%,表现出有统计学意义的脉络膜血管新生抑制作用。根据以上结果,能明确断定含有倍他米松的微球经结膜下给药,14天和28天后仍能表现出对脉络膜血管新生的抑制作用。
表2含有倍他米松微球的血管新生发生率(%)
对照组 | 微球组 | |
14天后 | 60.9±4.4 | 12.5±2.4 |
28天后 | 73.4±6.0 | 12.5±2.4 |
(表中,各组的血管新生发生率表示8只眼的平均值±标准偏差。)
产业上的可利用性
通过本发明能提供经结膜下给药的良好的眼球后部药物释放***。
Claims (12)
1、眼球后部药物释放***,其特征在于,含有药物的微粒是经结膜下给药的。
2、结膜下注射剂,所说注射剂含有含药的微粒,能使药物向眼球后部转移。
3、如权利要求1所述的药物释放***或权利要求2所述的结膜下注射剂,其中微粒的平均粒径为50nm~150μm。
4、如权利要求1所述的药物释放***或权利要求2所述的结膜下注射剂,其中微粒是由生物可降解性高分子或生物溶解性高分子制成的。
5、如权利要求1所述的药物释放***或权利要求2所述的结膜下注射剂,其中眼球后部是指视网膜、脉络膜、视神经、玻璃体或晶状体。
6、如权利要求1所述的药物释放***或权利要求2所述的结膜下注射剂,其中所述药物是用于治疗或预防视网膜、脉络膜、视神经、玻璃体或晶状体疾病的药物。
7、如权利要求1所述的药物释放***或权利要求2所述的结膜下注射剂,其中所述药物是抗炎剂、免疫抑制剂、抗病毒剂、抗癌剂、血管新生抑制剂、抗血栓剂、视神经保护剂、抗菌剂或者抗真菌剂。
8、眼球后部疾病的治疗和/或预防方法,所述方法包括在患者结膜下给予治疗有效剂量的含有含药微粒的注射剂。
9、如权利要求8所述的眼球后部疾病的治疗和/或预防方法,其中微粒的平均粒径为50nm~150μm。
10、如权利要求8所述的眼球后部疾病的治疗和/或预防方法,其中微粒是由生物可降解性高分子或生物溶解性高分子制成的。
11、如权利要求8所述的眼球后部疾病的治疗和/或预防方法,其中眼球后部是指视网膜、脉络膜、视神经、玻璃体或晶状体。
12、如权利要求8所述的眼球后部疾病的治疗和/或预防方法,其中所述药物是抗炎剂、免疫抑制剂、抗病毒剂、抗癌剂、血管新生抑制剂、抗血栓剂、视神经保护剂、抗菌剂或抗真菌剂。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002046355 | 2002-02-22 | ||
JP46355/2002 | 2002-02-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1638734A true CN1638734A (zh) | 2005-07-13 |
Family
ID=27750627
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA038044064A Pending CN1638734A (zh) | 2002-02-22 | 2003-02-21 | 微粒结膜下给药的药物释放*** |
Country Status (13)
Country | Link |
---|---|
US (1) | US20050089545A1 (zh) |
EP (1) | EP1484054B1 (zh) |
KR (2) | KR20040084931A (zh) |
CN (1) | CN1638734A (zh) |
AU (1) | AU2003211238A1 (zh) |
CA (1) | CA2476935C (zh) |
CY (1) | CY1113423T1 (zh) |
DK (1) | DK1484054T3 (zh) |
ES (1) | ES2393086T3 (zh) |
PT (1) | PT1484054E (zh) |
SI (1) | SI1484054T1 (zh) |
TW (1) | TWI290835B (zh) |
WO (1) | WO2003070219A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1771913B (zh) * | 2005-10-30 | 2011-07-20 | 沈阳药科大学 | 用乳化溶剂扩散法制备掩味微球的制备方法 |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004103478A1 (en) * | 2003-05-20 | 2004-12-02 | Collins James F | Ophthalmic drug delivery system |
US8012136B2 (en) | 2003-05-20 | 2011-09-06 | Optimyst Systems, Inc. | Ophthalmic fluid delivery device and method of operation |
WO2005018608A1 (ja) * | 2003-08-20 | 2005-03-03 | Santen Pharmaceutical Co., Ltd. | 微粒子テノン嚢下投与ドラッグデリバリーシステム |
AU2005209201B2 (en) * | 2004-01-20 | 2010-06-03 | Allergan, Inc. | Compositions for localized therapy of the eye, comprising preferably triamcinolone acetonide and hyaluronic acid |
US20060110428A1 (en) | 2004-07-02 | 2006-05-25 | Eugene Dejuan | Methods and devices for the treatment of ocular conditions |
EP1867334A4 (en) * | 2005-02-18 | 2009-07-15 | Santen Pharmaceutical Co Ltd | METHOD FOR RELIEVING OR AVOIDING A SECONDARY EFFECT OF A STEROID COMPOUND |
WO2006110487A1 (en) | 2005-04-08 | 2006-10-19 | Surmodics, Inc. | Sustained release implants for subretinal delivery |
JP4982839B2 (ja) * | 2005-06-22 | 2012-07-25 | 国立大学法人京都大学 | 硝子体可視化剤 |
US20090036552A1 (en) * | 2005-07-29 | 2009-02-05 | Santen Pharmaceutical Co. Ltd. | Noninvasive Drug Delivery System To Tissue of Posterior Segment of Eye Using Solid Composition |
US20070202186A1 (en) | 2006-02-22 | 2007-08-30 | Iscience Interventional Corporation | Apparatus and formulations for suprachoroidal drug delivery |
EP2255788B1 (en) * | 2008-02-29 | 2015-07-22 | Nagoya Industrial Science Research Institute | Liposome for delivery to posterior segment of eye and pharmaceutical composition for disease in posterior segment of eye |
JP5890182B2 (ja) | 2009-02-12 | 2016-03-22 | インセプト エルエルシー | ヒドロゲルプラグによる薬物送達 |
ES2835886T3 (es) | 2010-07-15 | 2021-06-23 | Eyenovia Inc | Dispositivo generador de gotas |
EA201390121A8 (ru) | 2010-07-15 | 2014-02-28 | Коринтиан Офтэлмик, Инк. | Способ и система для выполнения дистанционного лечения и контроля |
KR20130051476A (ko) | 2010-07-15 | 2013-05-20 | 코린시언 아프샐믹 인코포레이티드 | 안과용 약물 전달 |
US10154923B2 (en) | 2010-07-15 | 2018-12-18 | Eyenovia, Inc. | Drop generating device |
JP5996544B2 (ja) | 2010-10-15 | 2016-09-21 | クリアサイド・バイオメディカル・インコーポレーテッドClearside Biomedical Incorporated | 眼球アクセス用装置 |
KR20190090048A (ko) | 2011-12-05 | 2019-07-31 | 인셉트, 엘엘씨 | 의료용 유기젤 방법 및 조성물 |
JP5960840B2 (ja) | 2011-12-12 | 2016-08-02 | アイノビア,インコーポレイティド | エジェクタ機構、エジェクタ装置及びそれらの使用方法 |
CN104884049A (zh) | 2012-11-08 | 2015-09-02 | 克莱尔塞德生物医学股份有限公司 | 用于在人类受试者中治疗眼部疾病的方法和装置 |
WO2014179615A2 (en) * | 2013-05-01 | 2014-11-06 | Dae Won Park | Biodegradable copolymers, systems including the copolymers, and methods of forming and using same |
MX2015015282A (es) | 2013-05-03 | 2016-02-26 | Clearside Biomedical Inc | Aparatos y metodos para inyeccion ocular. |
US10010447B2 (en) | 2013-12-18 | 2018-07-03 | Novartis Ag | Systems and methods for subretinal delivery of therapeutic agents |
AU2015289387B2 (en) | 2014-07-18 | 2020-10-22 | Allergan, Inc. | Suspension compositions of cyclosporin A for subconjunctival and periocular injection |
GB201522441D0 (en) | 2015-12-18 | 2016-02-03 | Midatech Pharma Wales Ltd | Sustained release cyclosporine-loaded microparticles |
US10390901B2 (en) | 2016-02-10 | 2019-08-27 | Clearside Biomedical, Inc. | Ocular injection kit, packaging, and methods of use |
EP3452165A1 (en) | 2016-05-02 | 2019-03-13 | Clearside Biomedical, Inc. | Systems and methods for ocular drug delivery |
CN110177527B (zh) | 2016-08-12 | 2022-02-01 | 科尼尔赛德生物医学公司 | 用于调节药剂递送用针的***深度的装置和方法 |
CN115300226A (zh) | 2017-06-10 | 2022-11-08 | 艾诺维亚股份有限公司 | 用于将一体积的流体输送到眼睛的设备 |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3960150A (en) * | 1971-09-09 | 1976-06-01 | Alza Corporation | Bioerodible ocular device |
US5702716A (en) * | 1988-10-03 | 1997-12-30 | Atrix Laboratories, Inc. | Polymeric compositions useful as controlled release implants |
US5185152A (en) * | 1990-01-10 | 1993-02-09 | Peyman Gholam A | Method and apparatus for controlled release drug delivery to the cornea and anterior chamber of the eye |
US5384333A (en) * | 1992-03-17 | 1995-01-24 | University Of Miami | Biodegradable injectable drug delivery polymer |
US5178635A (en) * | 1992-05-04 | 1993-01-12 | Allergan, Inc. | Method for determining amount of medication in an implantable device |
US5700485A (en) * | 1992-09-10 | 1997-12-23 | Children's Medical Center Corporation | Prolonged nerve blockade by the combination of local anesthetic and glucocorticoid |
US5922340A (en) * | 1992-09-10 | 1999-07-13 | Children's Medical Center Corporation | High load formulations and methods for providing prolonged local anesthesia |
HU220864B1 (en) * | 1993-04-16 | 2002-06-29 | Wakamoto Pharma Co Ltd | Reversible, thermally gelling water-base medicinal compositions |
SE9401108D0 (sv) * | 1994-03-31 | 1994-03-31 | Leiras Oy | Ophthalmic composition I |
US5466233A (en) * | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
JPH08176016A (ja) * | 1994-12-19 | 1996-07-09 | Univ Miami | 生分解可能で注射可能な薬物運搬ポリマー |
US5869079A (en) * | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
US6264970B1 (en) * | 1996-06-26 | 2001-07-24 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
EP0959873B1 (en) * | 1996-12-20 | 2006-03-01 | ALZA Corporation | Gel composition and methods |
US6378526B1 (en) * | 1998-08-03 | 2002-04-30 | Insite Vision, Incorporated | Methods of ophthalmic administration |
JP2000247871A (ja) | 1999-02-25 | 2000-09-12 | Santen Pharmaceut Co Ltd | 網膜または硝子体への薬物放出制御システム |
US6395294B1 (en) * | 2000-01-13 | 2002-05-28 | Gholam A. Peyman | Method of visualization of the vitreous during vitrectomy |
JP2002326962A (ja) * | 2000-04-03 | 2002-11-15 | Santen Pharmaceut Co Ltd | 送達性物質およびそれを利用した薬物デリバリーシステム |
US20030194421A1 (en) * | 2001-12-28 | 2003-10-16 | Angiotech Pharmaceuticals, Inc. | Treatment of uveitis |
-
2003
- 2003-02-21 EP EP03705377A patent/EP1484054B1/en not_active Expired - Lifetime
- 2003-02-21 AU AU2003211238A patent/AU2003211238A1/en not_active Abandoned
- 2003-02-21 CA CA2476935A patent/CA2476935C/en not_active Expired - Fee Related
- 2003-02-21 ES ES03705377T patent/ES2393086T3/es not_active Expired - Lifetime
- 2003-02-21 CN CNA038044064A patent/CN1638734A/zh active Pending
- 2003-02-21 PT PT03705377T patent/PT1484054E/pt unknown
- 2003-02-21 US US10/505,393 patent/US20050089545A1/en not_active Abandoned
- 2003-02-21 KR KR10-2004-7013018A patent/KR20040084931A/ko active Search and Examination
- 2003-02-21 TW TW092103600A patent/TWI290835B/zh not_active IP Right Cessation
- 2003-02-21 SI SI200332201T patent/SI1484054T1/sl unknown
- 2003-02-21 WO PCT/JP2003/001897 patent/WO2003070219A1/ja active Application Filing
- 2003-02-21 DK DK03705377.4T patent/DK1484054T3/da active
- 2003-02-21 KR KR1020107019620A patent/KR20100102749A/ko not_active Application Discontinuation
-
2012
- 2012-11-27 CY CY20121101142T patent/CY1113423T1/el unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1771913B (zh) * | 2005-10-30 | 2011-07-20 | 沈阳药科大学 | 用乳化溶剂扩散法制备掩味微球的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
AU2003211238A1 (en) | 2003-09-09 |
CA2476935C (en) | 2013-05-28 |
PT1484054E (pt) | 2012-11-28 |
CY1113423T1 (el) | 2016-06-22 |
KR20100102749A (ko) | 2010-09-24 |
KR20040084931A (ko) | 2004-10-06 |
SI1484054T1 (sl) | 2012-12-31 |
DK1484054T3 (da) | 2012-11-26 |
TW200303218A (en) | 2003-09-01 |
TWI290835B (en) | 2007-12-11 |
EP1484054B1 (en) | 2012-08-29 |
EP1484054A4 (en) | 2007-12-12 |
EP1484054A1 (en) | 2004-12-08 |
US20050089545A1 (en) | 2005-04-28 |
CA2476935A1 (en) | 2003-08-28 |
WO2003070219A1 (fr) | 2003-08-28 |
ES2393086T3 (es) | 2012-12-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1638734A (zh) | 微粒结膜下给药的药物释放*** | |
JP6700348B2 (ja) | 持続型薬物送達インプラント | |
CN100453066C (zh) | 利用结膜下储存库的药物释放*** | |
US20060013859A1 (en) | Drug delivery system using subconjunctival depot | |
JP5437563B2 (ja) | 眼の後部の処置のための組成物および方法 | |
US20150265633A1 (en) | Steroid containing drug delivery system | |
BRPI0708622A2 (pt) | terapia ocular usando agentes que ativam a sirtuina | |
CN102497865A (zh) | 用于治疗眼部病症的眼内缓释药物递送***和方法 | |
Gavini et al. | Biodegradable microspheres as intravitreal delivery systems for prolonged drug release. What is their eminence in the nanoparticle era? | |
CN1835735B (zh) | 微粒眼球筋膜下给药的药物释放*** | |
JP4228195B2 (ja) | 微粒子結膜下投与ドラッグデリバリーシステム | |
Herrero-Vanrell | Microparticles as drug delivery systems for the back of the eye | |
Naveed et al. | Contemporary trends in novel ophthalmic drug delivery system: An overview | |
JP2005097275A (ja) | 微粒子テノン嚢下投与ドラッグデリバリーシステム |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication |