CN1046094C - 多糖体用于制备原位胶凝的眼科组合物的用途 - Google Patents
多糖体用于制备原位胶凝的眼科组合物的用途 Download PDFInfo
- Publication number
- CN1046094C CN1046094C CN86106637A CN86106637A CN1046094C CN 1046094 C CN1046094 C CN 1046094C CN 86106637 A CN86106637 A CN 86106637A CN 86106637 A CN86106637 A CN 86106637A CN 1046094 C CN1046094 C CN 1046094C
- Authority
- CN
- China
- Prior art keywords
- purposes
- ophthalmic composition
- polysaccharide body
- liquid
- active substances
- 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.)
- Expired - Lifetime
Links
Images
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/04—Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds
-
- 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
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
Abstract
本发明涉及一种为与生理液进行接触的药物组合物,其特征是所述的组合物是以非胶凝化的液体形式被施用并在原位形成凝胶的,本组合物含有至少一种处于水溶液状态的多糖体,在所述生理液的离子强度增加的作用下这类水溶液会在原位发生液-胶相转变的胶凝作用。
Description
本发明涉及一种多糖体用于制备原位胶凝的眼科组合物的用途,所述眼科组合物含有至少一种多糖体水溶液,这类水溶液在离子强度增加的作用下会进行液-胶相的转变。
本发明的眼科组合物类型是属于在离子强度增加的作用下会进行液-胶相转变的类型。
它们被特别地用作与生理液进行接触。由于生理液的渗透强度比所说组成中的一种来得高,因此就在接触时发生了相转变。
本发明的组合物特别适用于眼内使用,但也能以可注射的形式进行使用,所形成的胶体具有缓慢释放的功能,正如可通过皮内或肌内注射,或者是以与粘膜进行接触的盖伦氏制剂的形式进行使用。
由于眼泪的排放会使施用到眼内的药物损失较大的百分比,而在液体配方的情况下就更是如此。在效果上,作为这种排放的结果,所施用的剂量中只有一小部分能继续与角膜接触数分钟,而只有更小的一部分渗透进眼内。
为了克服这一缺点,已知的方法是采用粘性渗液、凝胶、眼药膏或固态的眼内植入物。
迄今,在供给药物方法方面已经有了一些进展,具体是通过采用盖伦氏制剂的形式,尤其是采用固体植入法,通过这些途径就能大大降低配方中的活性物质的剂量而使疗效与需使用洗眼液剂的情况保持相同,但后者需要被更频繁地施用。
这些植入物中的一些是通过扩散来发挥作用的。例如在“O-CUSERT”系统中,每周在结膜囊中植入一卵圆形镜片可以使活性物质通过扩散而输送出来,但该镜片在使用后必须移去,因为它对病人来说是产生问题的根源。
其它植入物是可溶解的,在这种情况下由于植入物不是可诱性的就是能自动降解的(“LACRISERT”系统),因此反应的时间就更短了。
在一切情况下,固体植入物的主要缺点是病人难以忍受把固态物植入结合膜的凹陷。
为了解决这一问题,可以采用盖伦氏制剂的形式,它在室温下为液体而在人体温度下形成半固体状态。这种输入系统已在美国专利4,188,373中得到了描述,该专利建议使用“PLURONIC多元醇”。
这些“PLURONIC多元醇”经加热后呈凝胶性聚合物,其中聚合物的浓度是根据所需的液-胶相的转变温度来选定的。
然而,就商业上可得到的“PLURONIC聚合物”来说,就难以在使转变温度保持在生理温度(在25~36℃的范围内)的情况下获得合适硬度的凝胶。
同样地,加拿大专利1,072,413也描述了含有一种治疗剂或其他药剂(Poloxamer,系一种表面活性剂)的系统,通过加入添加剂可使其胶凝温度高于室温。
热凝胶系统有着许多缺点,例如在施用前由于包装或贮藏过程中环境温度的上升就有可能发生凝胶。
默克公司(Merck&Co)的美国专利4,474,751叙述到了基于凝胶的热凝胶作用的药物释放系统,但这些系统需要十分大量的聚合物,而这这并不是眼睛所能忍受的。
本发明涉及一种多糖体用于制备能与生理液进行接触的药物组合的用途,其特征在于所说的组合物是以非胶凝化的液体形式被施用并在原位置胶凝的,该组合物含有至少一种多糖体水溶液,这类水溶液在所说生理液的离子强度增加的作用下会在原位发生液-胶相转变。
本发明所优先选用的药物组合物是一种用于眼科学的组合物,而生理液为泪液。于是,本发明克服了这些施用眼科用组合物的特殊问题。
事实上,那些在移入眼内之前呈液体形式的组合物会发生液-胶相转变,于是就从液相转变为胶体相,一旦它被引入眼内,就会由于存在于本情况的生理液流的泪液的离子强度而变成凝胶。
这种新的眼科学组合物从几种理由来看有着惊人的优点。尤其是,由于有泪液存在下可导致凝胶形成,所以溶液在眼外的偶然流失都不会形成凝胶。再者,它与热凝胶系统相反,贮存过程中环境温度的上升是不会导致溶液发生胶凝的。
另外,所采用的聚合物能形成其浓度比包括热凝胶的系统中所使用的那些低10~100倍的凝胶。所以这对眼睛来说是很好受的。
最后,当这些组合物含有药用活性物质时,这样的释放系统就有可能获得很大的产品生物利用度和随时间的延长维持主要活性物质的浓度,这即为缓慢释放系统的优点。
再者,在已胶凝化的或半固体的组合物的情况下,这就不可能以测定体积的方式来施用它们,尤其是当它们来自多种剂量盛器时就更是如此。为了可重复地定量施用这些组合物,人们就不得不采用测重量的方法。
本发明的组合物一方面具有液态眼用组合物的优点,即可通过测体积法对活性物质进行可重复地和精确的投配,另一方面具有对处于坚硬的或半固体凝胶形式的物系来说是已知的优点,即涉及了活性物质的释放。
本发明的组合物于是既没有简单液体组合物中活性物质特性的损失这种缺点,也没有固体植入物系统的令人难以接受之处,最后也不存在与胶凝化或半固体组合物有关的药物在施用方面的困难。
该申请人公司已经通过实验证实了那种多糖体水溶液,这种类型的多糖体水溶液在离子强度增加的作用下会发生液-胶相转变,根据本发明它们是尤为适合的多糖体液流,可通过微生物发酵而获得。
于是,本发明优先使用的是由假单胞菌(elodea)所合成并被称为胶凝树胶(gellen gum)的细胞外的阴离子杂多糖体。
这种由KELCO公司制造的多糖体已经被用作培养基的胶凝剂,并且也用于食品。这种杂多糖体的结构由以下重复单元的四多糖体构成。
→3)-β-D-Glcp-(1→4)-β-D-GlcopA-(1→4)-β-D-Glcp-(1→4)-a-L-Rhap-(1→
这可以或不可以部分地在它的β-D-吡喃(型)葡萄糖(β-D-Glcp)残基上接受氧-乙酰化。
固有的多糖体和脱乙酰多糖体的制备是在美国专利4,326,053和4,326,052中得到了描述的,这二件专利分别属于默克(MERK)公司和赖维(Rahwag N·J)公司,而它们的结构已被描述在〔JANS-SON和LINDBERG,Carbohydr.res.124(1983)135-9〕。
根据本发明,含有约0.1%~约2.0%(重量)的胶凝树胶,尤其是那些商品名称为Gelrite的产品(它是属于乙酰基澄清级的胶凝树胶)在低离子强度下为胶液,当离子强度增加时会产生液-胶相转变而成凝胶,而当这种水溶液滴入眼内时就是这种情况。
凝胶的硬度可通过调整聚合物浓度来加以改变。
胶凝树胶产品不但具有在被放置于高离子强度的介质时能够从液态变为固态的性质,而且也具有本发明的附加的优异特性。
在效果上,水溶液中的Gelrits为具有摇溶性的(图1)和热塑性的(图2)。
这两种性质可通过摇动或在施用于眼睛之前稍微加热来增加它的流动性。
图1表明了20℃时0.6%Gelrits水溶液的流变情况(剪切应力(Pa)对剪切速率(秒-1))的关系。
图2表明了在进行了30%稀释之后0.6%Gelrits溶液的(剪切应力(Pa)与温度(℃)的关系〔在86秒-1的恒定剪切速率下〕,稀释液为
1)蒸馏水
2)模拟的泪液。
图2.2)的后一种情况显示了因Gelrits在模拟的泪液中的稀释而导致的粘度增加。
于是,申请人公司把含有0.4%(重量)的Gelrits的溶液的20微升滴注入去离子水中,施用于兔子后在兔子的眼睛中出现了凝胶的形成。
本发明的眼用组合物也可作其他各种应用,例如可以维持眼睛足够的水合效应(干眼综合症的治疗)。
更进一步讲,根据本发明的眼用组合物看来特别适合于为了治疗和/或诊断的目的把任何药用活性的物质施入眼内。于是本发明涉及了含有至少一种用于治疗或诊断目的药用活性物质的药物组合物。
至于药用活性物质,这里有已被理解的一种或更多的药物和/或一种或多种诊断剂。任何活性物质可通过本发明的组合物来释放。该活性物质优先选用的为可水溶性的,尽管根据本发明来说某些活性物质比多糖体水溶液中的其他组分显示了更大的可溶性。再者,活性物质在多糖体水溶液中能形成悬浮液或乳化液(例如,油滴、复合的类脂体物质以及类脂体的乳化液)。于是,本发明涉及了含有至少一种活性物质的多糖体水溶液中的溶液、悬浮液或乳化液。
根据本发明所使用的理想的药用活性物质为噻吗心安或它的衍生物。
噻吗心安可被单独使用或与其他药学活性剂结合着使用。
本发明所涉及的眼用组合物最好是含有约0.1%~约2.0%(重量)的上述多糖体和约0.001%~约5%(重量)的至少一种药用活性物质。
胶凝树胶水溶液中有关胶凝树脂的用量以能获得合适的凝胶并能补尝因制造这些眼用组合物的消毒过程所造成的损失为度。
根据本发明,也可在该眼用组合物中使用其他添加剂。这些尤其是那些适合于眼睛局部施用的聚合物、少量的酸或碱以便把PH值调整到可施用于眼睛的程度、非离子型渗透度调节剂、表面活性剂、用于控制细菌污染的药剂或例如,为使活性物质能溶解或稳定的其他添加剂或参与该配方组成的一些其他添加剂。
如有必要,离子化活性物质的凝胶诱发作用,例如被结合进本发明组合物的活性物质的凝胶诱发作用可通过把能形成合适的离子对的药剂加入该组合物而得到中和。
例如,通过加入少量的醋酸可消除由于把0.1毫克/毫升的氯苄烷铵被加入到本发明的Gelrits溶液中所引起的轻微胶凝作用。本申请人公司另外还例证了,本发明的Gelrits溶液与其他的配方组份如各种缓冲剂以及可以形成离子对的药剂是相容的。
正如将会在实施例中看到的那样,甘露醇可以被使用在本发明的组合物中从而调整介质的渗透度而不改变胶凝性质。
其他的渗透度调节剂也可被使用,例如山梨糖醇或其他一些糖类。
为了能使它们能被施用到眼内,本发明的眼用组合物是以液体的形式以传统的方法通过药滴进行施用的,例如用眼滴管或例如所谓的“OCUMETER”系统。
本发明的组合物可以通过通常的冲洗眼睛的方式被施用,被施用在眼睛外部的结合膜的下角凹陷。
通过实施例的方法,一滴含有约25毫克眼用组合物的液体组合物能使约0.0025毫克~约1.25毫克的活性物质得到施用。
使用在本发明的药物组合物中的活性物质为药物或诊断剂,最好能合适地用于治疗病人所遭到的疾病和/或用于所希望使用的诊断方法。
例如,假如病人正患青光眼,活性物质最好被选择为β-阻带剂,例如噻吗心安或它的一种衍生物。
毒理学研究证明了胶凝树胶的良好的可耐性:鼠中的急性口服毒性试验表明致死的剂量50(LD50)大于5000毫克/公斤;采用吸入剂进行的急性毒性试验表明把鼠暴露在6.09毫克/升的额定浓度中达4小时不会引起10只一组的动物中任何一只的死亡,这表明致死浓度50(LD)大于6.09毫克/升。
鼠中的DRAIZE-型眼睛刺激试验表明该产品不能被认为是眼睛刺激剂。
当这些组合物含有活性物质时,这种系统的目的是要释放该活性物质而能获得物质的大的生物利用度,并能随时间的延长而维持这种物质的浓度。
能够通过本发明的眼用组合物的途径被施用的药物或诊断剂为:例如:抗菌的物质,例如β-内酰胺类抗生素,如头孢甲氧霉素、n-甲酰胺基噻吩霉素和其他噻吩霉素的衍生物、四环类抗菌素、氯霉素、新霉素、羧苄青霉素、粘菌素、青霉素G、多粘菌素B、万古霉素、唑啉头孢先锋霉素-Ⅱ、Chibro利福霉素(chibro rifamycin)、短杆菌肽、〔枯草〕杆菌肽及磺胺类药物。氨基糖苷类抗生素,例如庆大霉素、卡那霉素、丁胺卡那霉素、紫苏霉素和托普霉素;荼啶酮酸和它的类似物,例如诺弗卡新(norfloxacin)和抗微生物的复合物氟丙氨酸木的西酮(penti zidone)(一种抗菌药物)、硝基呋咱酮和它们的类似物;抗组胺剂和减充血剂,例如吡野生麻花碱、扑尔敏、四氢荼唑啉、安他唑啉以及它们的类似物;抗炎剂,例如可的松、氢化可的松、氢可的松乙酸醋、β米松、地塞米松、地塞米松磷酸钠、强的松、甲基强的松、6α-甲-11β羟孕酮、氟甲龙、脱氢皮质醇、脱氢皮质醇磷酸钠、氟羟脱氢皮醇、消炎痛、苏灵大、它们的盐和相应硫化物及其同类物;缩瞳药和抗胆碱能剂,例如二乙氧膦酰硫胆碱、毛果〔芸香〕碱、毒扁豆碱木杨酸盐、二异丙基氟磷酸盐、肾上腺素、二叔戊酰肾上腺素、新斯的明、碘化二乙氧膦酰硫胆碱、溴化癸二胺苯酯、氨基甲酰氨胆碱、乙酰甲基胆碱、北参考、和它们的同类物。瞳孔放大药,例如阿托品、后乌托品、东莨菪碱、羟基苯异丙胺、麻磺素、可卡因、托品酰胺、苯基麻磺素、环五醇酯、羟苯乙铵、优加托品及其同类物;
用于治疗眼睛状况及病灶的其他药物有例如:
抗青光眼药物,例如噻吗心安,尤其是它的马来酸盐和R-噻吗心安以及噻吗心安或R-噻吗心安与毛果〔芸香〕碱的结合体,还有许多其它肾上腺素类的兴奋剂和/或抗兴奋剂;肾上腺素和一肾上腺素复合体,或前体药物如酒石酸氢盐、硼酸盐、盐酸盐和3,4二氢-α(甲胺基)甲苄醇3,4双新戊酸(Dipivefrine)微生物和滴渗剂如甘油、甘露醇和尿素;碳酸脱氢酶抑制剂如乙酰唑(磺)酰胺、二氯苯二乙酰胺、2-(对一羟基苯基)-噻-5硫代氨磺酰胺、6-羟基-2-苯并噻唑磺酰胺和6-新戊酰氧基-2-苯并噻唑磺酰胺。抗寄生物的和/或抗原虫的化合物例如双氢麦菌素(Ivermectin)嘧啶甲胺、三磺基嘧啶、(Trisulfa-pidimidine),氯林可霉素及类皮留醇制品.有抗病毒活性的化合物
例如9(2一羟基乙氧甲基尿嘌呤)、碘代-2’-脱氧尿苷(IDU)、腺甙阿拉伯
甙(Ara-A)、三氟胸苷、和干扰素以及诱导干扰素的药物剂如素I:C;抗霉剂,例如两性雷素B、制霉菌素、氟胞嘧啶、游霉素和双氯苯咪唑;麻醉剂,例如依铁卡因可卡因、丁氧普普卡因、双白卡因盐酸盐、达克罗宁丁氧苯哌啶丙酮盐酸盐、2(戊铵基)乙醇一对位铵基苯甲酸、非那卡因盐酸盐、胡椒卡因、丙对卡因盐酸盐、阿美素卡因盐酸盐、已基卡因、丁哌卡因、利多卡因、美吡佛卡因和丙胺卡因;眼科诊断剂.例如a)用于检查视网膜的药物如荧光素钠;b)用于检查结合膜、角膜和泪器的药物如荧光素和玫瑰琼脂;c)用于检查不正常瞳孔反应的药物如乙酰甲胆碱、可卡因、肾上腺(激)素、阿托品、羟基苯丙胺和毛果〔芸香〕碱;外科手术中用于结合膜的眼科药剂,如α-胰凝乳蛋白酶原和透明质酸酶螯合剂例如乙二胺四乙酸(EDTA)和去铁胺免疫抑制剂和抗代谢物剂,例如氨甲叶酸、环磷酰胺、6-琉基嘌呤和咪唑嘌呤;和上述化合物的复合物,例如抗生素/消炎剂的混合物如新霉素硫酸盐和地塞米松磷酸钠的复合物、和伴随着治疗青光眼的混合药剂,例如噻吗心安马来酸酯和喹核醇乙酸酯的混合物。
一般来说,由眼睛所产生的眼泪稀释了活性物质并很快地耗尽被传统的液态溶液所引入的活性物质。
以本发明的水溶液状含有多糖体的组合物属于这样一种类型,即在离子强度增加的作用下能发生液-胶的相转变,对这种组合物进行慢慢地稀释并使之能够对溶解或悬浮在该组合物中的活性物质进行持续的释放(为实现这一目的,就必须使组合物中的总的离子强度保持得尽可能低)。这样,本发明的组合物所允许的延长了的停留时间就使得泪膜中活性物质的浓度达到更有效水平。
说明了本发明的组合物中的活性物质在滴入眼睛之后能持续地存在、以及说明了本发明的其它特征和优点的试验显示在以下的实施例和图中,这些实施例和附图例证了本发明。(百分数是以重量计算的)实施例1简单的眼用组合物
溶液1 溶液2 溶液3
-Gelrite 0.6% 0.6% 0.2%
-氯化苄烷铵 0.01% 0.05%
-甘露醇 4% 4%
-足量水加 100% 100% 100%实施例2释放噻吗心安的组合物
溶液1 溶液2 溶液3-噻吗心安马来酸 0.34% 0.65% 0.34%盐-Gelrite 0.6% 0.6% 0.6%-氯化苄烷铵 0.01% 0.01%-甘露醇 4% 4% 4%一足量水加至 100% 100% 100%实施例3释放地塞米松磷酸盐的组合物
溶液1 溶液2 溶液3-地塞米松磷酸盐 0.1% 0.05% 0.1%-Gelrite 0.6% 0.3% 0.6%-氯化苄烷铵 0.01% 0.01% 0.01%-甘露醇 4% 4% 4%-足量水加 100% 100% 100%实施例4
为了就掺入本发明组合物中的活性物质在滴入眼睛之后对它在眼中可持续地存在的情况进行说明,特进行了一个比较试验。
用蒸馏水或含有0.6%Gelrite的媒介物,在荧光素溶液滴入兔子眼睛之后把荧光素从兔子的结合膜凹陷清除掉,最后通过远紫外辐射进行观察。
在用水溶液处理过的眼睛中,滴入的3小时后没有发现荧光素仍存在,而在用含有Gelrite的载体处理过的眼睛中,滴入的5个小时后荧光素仍然存在。实施例5用于释放噻吗心安的组合物
为了在体内试验得到噻吗心安的生物利用度的数据,分别在患白化病的兔中单次注入50毫升Gelrite配方组合物(例2溶液1)及Timoptic商品溶液。每种含有0.25%噻吗心安,测定兔子体液中的噻吗心安浓度以作对比,其中Gelrite溶液系由三种不同批号的Gelrite聚合体制成。
本发明并不局限于上述实施例,本发明的组合物也适合于应用在所有为与生理液进行接触的药物组合物中。
因此,本发明还涉及用于皮内或肌内注射的可注射组合物和为与粘膜进行接触的外局部用组合物。
Claims (13)
1.一种多糖体用于制备眼科组合物的用途,所述眼科组合物以与泪液进行接触的、非胶凝化的液体形式被施用、并在原位发生胶凝,其特征在于,所述眼科组合物包括用于眼科的载体和至少一种水溶液状的多糖体,该多糖体在所说的泪液的离子强度增大的作用下,在原位发生液一胶相转变的胶凝。
2.根据权利要求1所述的用途,其特征是,所述多糖体是通过微生物的发酵而得到的。
3.根据权利要求2所述的用途,其特征是,所述微生物为假单细胞菌属的伊乐藻属。
4.根据权利要求1或3所述的用途,其特征是,所述的多糖体具有其基本的四糖单元,即→3)-β-D-Glcp-(1→4)-β-D-GlcpA-(1→4)-β-D-Glcp-(1→4)-α-L-Rhap-(1→,该四糖单元可以或不可以在β-D-吡喃型葡萄糖残基体上被部分地氧-乙酰化。
5.根据权利要求1所述的用途,其特征是,所述的眼科组合物中含有0.1~2.0%(重量)的上述多糖体。
6.根据权利要求1所述的用途,其特征是,所述的眼科组合物中包括加入有渗透度调节剂。
7.根据权利要求6所述的用途,其特征是,所述的渗透度调节剂为甘露糖醇或山梨糖醇这样的糖。
8.根据权利要求6所述的用途,其特征是,所述的眼科组合物中包括加入至少一种用于治疗或诊断目的的药学活性物质。
9.根据权利要求8所述的用途,其特征是,所加入的药学活性物质为噻吗心安或它的衍生物。
10.根据权利要求8或9所述的用途,其特征是所述眼科组合物中包括混合0.1%~2%(重量)的多糖体和至少一种用于治疗或诊断目的的0.001~5%(重量)的药学活性物质。
11.根据权利要求8~10中的任何一项所述的用途,其特征是所说的药学活性物质是处于溶液中的。
12.根据权利要求8~10中的任何一项所述的用途,其特征是药用活性物质是处于悬浮液中的。
13.根据权利要求8~10中的任何一项所述的用途,其特征是药学活性物质处于乳化液中。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR85-14689 | 1985-10-03 | ||
FR8514689A FR2588189B1 (fr) | 1985-10-03 | 1985-10-03 | Composition pharmaceutique de type a transition de phase liquide-gel |
FR8514689 | 1985-10-03 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN86106637A CN86106637A (zh) | 1987-04-08 |
CN1046094C true CN1046094C (zh) | 1999-11-03 |
Family
ID=9323509
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN86106637A Expired - Lifetime CN1046094C (zh) | 1985-10-03 | 1986-09-30 | 多糖体用于制备原位胶凝的眼科组合物的用途 |
Country Status (25)
Country | Link |
---|---|
US (1) | US4861760A (zh) |
EP (1) | EP0227494B1 (zh) |
JP (1) | JPH0667853B2 (zh) |
KR (1) | KR940000229B1 (zh) |
CN (1) | CN1046094C (zh) |
AT (1) | ATE72990T1 (zh) |
AU (1) | AU595240B2 (zh) |
CA (1) | CA1280367C (zh) |
CY (1) | CY1779A (zh) |
DE (2) | DE227494T1 (zh) |
DK (1) | DK170500B1 (zh) |
ES (1) | ES2002401A6 (zh) |
FI (1) | FI91217C (zh) |
FR (1) | FR2588189B1 (zh) |
GR (1) | GR862444B (zh) |
HK (1) | HK42594A (zh) |
IE (1) | IE59464B1 (zh) |
IL (1) | IL80156A (zh) |
LU (1) | LU88694I2 (zh) |
LV (1) | LV5725B4 (zh) |
NL (1) | NL950012I1 (zh) |
NO (2) | NO173212C (zh) |
NZ (1) | NZ217662A (zh) |
PT (1) | PT83471B (zh) |
ZA (1) | ZA867464B (zh) |
Families Citing this family (361)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5095026A (en) * | 1983-02-04 | 1992-03-10 | University Of Iowa Research Foundation | Prodrugs of carbonic anhydrase inhibitors |
US5200180A (en) * | 1987-06-26 | 1993-04-06 | Christian Bannert | Pharmaceutical composition for the treatment of the human eye |
FR2618333B1 (fr) * | 1987-07-20 | 1990-07-13 | Merck Sharp & Dohme | Composition pharmaceutique et/ou cosmetique a usage topique contenant de la gomme rhamsam |
US5843156A (en) | 1988-08-24 | 1998-12-01 | Endoluminal Therapeutics, Inc. | Local polymeric gel cellular therapy |
US6436425B1 (en) | 1988-11-16 | 2002-08-20 | Mdv Technologies, Inc. | Method and non-gelling composition for inhibiting post-surgical adhesions |
US4911926A (en) * | 1988-11-16 | 1990-03-27 | Mediventures Inc. | Method and composition for reducing postsurgical adhesions |
US5034406A (en) * | 1989-09-26 | 1991-07-23 | Allergan, Inc. | Method for reducing or maintaining intraocular pressure |
US5521222A (en) * | 1989-09-28 | 1996-05-28 | Alcon Laboratories, Inc. | Topical ophthalmic pharmaceutical vehicles |
US5461081A (en) * | 1989-09-28 | 1995-10-24 | Alcon Laboratories, Inc. | Topical ophthalmic pharmaceutical vehicles |
FR2653021A1 (fr) * | 1989-10-17 | 1991-04-19 | Merck Sharp & Dohme | Composition ophtalmique aqueuse liquide a transition de phase liquide-gel. |
FR2653018A1 (fr) | 1989-10-17 | 1991-04-19 | Merck Sharp & Dohme | Composition ophtalmique non solide a base de microparticules de polymere contenant au moins un principe actif en suspension dans un milieu dispersant et procede de preparation de ladite composition. |
US5141928B1 (en) * | 1989-12-20 | 1995-11-14 | Brujo Inc | Ophthalmic medication |
US5496471A (en) * | 1990-01-08 | 1996-03-05 | Ciba-Geigy Corporation | Apparatus for removing components from solutions |
FR2657018A1 (fr) * | 1990-01-12 | 1991-07-19 | Merck Sharp & Dohme | Composition ophtalmique fluide a base de microparticules lipidiques contenant au moins un principe actif et son procede de preparation. |
US5593683A (en) * | 1990-05-01 | 1997-01-14 | Mdv Technologies, Inc. | Method of making thermoreversible polyoxyalkylene gels |
US5298260A (en) * | 1990-05-01 | 1994-03-29 | Mediventures, Inc. | Topical drug delivery with polyoxyalkylene polymer thermoreversible gels adjustable for pH and osmolality |
US5252318A (en) * | 1990-06-15 | 1993-10-12 | Allergan, Inc. | Reversible gelation compositions and methods of use |
US5346703A (en) | 1990-08-07 | 1994-09-13 | Mediventures, Inc. | Body cavity drug delivery with thermo-irreversible polyoxyalkylene and ionic polysaccharide gels |
CA2044878C (en) * | 1990-08-07 | 2000-12-26 | Tacey X. Viegas | Thermally reversible and irreversible gels |
FR2665635A1 (fr) * | 1990-08-10 | 1992-02-14 | Merck Sharp & Dohme | Composition pharmaceutique fluide a base d'un complexe metallique et son procede de preparation. |
US5847023A (en) * | 1990-10-26 | 1998-12-08 | Mdv Technologies, Inc. | Thermal irreversible gel corneal contact lens formed in situ |
EP0495421B1 (en) * | 1991-01-15 | 1996-08-21 | Alcon Laboratories, Inc. | Use of carrageenans in topical ophthalmic compositions |
US5212162A (en) * | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
SG84487A1 (en) | 1991-04-17 | 2001-11-20 | Merck & Co Inc | Ophthalmic compositions comprising combinations of a carbonic anhydrase inhibitor and a b-adrenergic antagonist |
ZA927277B (en) * | 1991-10-02 | 1993-05-19 | Boston Ocular Res | Dry eye treatment process and solution. |
US5318780A (en) * | 1991-10-30 | 1994-06-07 | Mediventures Inc. | Medical uses of in situ formed gels |
RU2108112C1 (ru) * | 1993-04-16 | 1998-04-10 | Вакамото Фармасьютикал Ко., Лтд. | Водная лекарственная композиция, обладающая свойством обратимого терморегулируемого гелеобразования |
SE9301877D0 (sv) * | 1993-06-02 | 1993-06-02 | Kabi Pharmacia Ab | In situ gel for therapeutic use |
US5545617A (en) * | 1993-11-12 | 1996-08-13 | The Schepens Eye Research Institute, Inc. | Therapeutic regulation of abnormal conjunctival goblet cell mucous secretion |
JP2742333B2 (ja) * | 1994-05-06 | 1998-04-22 | アルコン ラボラトリーズ,インコーポレイテッド | 眼科用組成物におけるビタミンeトコフェリル誘導体の使用 |
IL114193A (en) * | 1994-06-20 | 2000-02-29 | Teva Pharma | Ophthalmic pharmaceutical compositions based on sodium alginate |
US5585398A (en) * | 1994-07-15 | 1996-12-17 | Ernst; Amy A. | Topical anesthetic comprising lidocaine, adrenaline, and tetracaine, and its method of use |
US6316443B1 (en) | 1994-08-04 | 2001-11-13 | Merck & Co., Inc. | Ophthalmic compositions comprising combinations of a carbonic anhydrase inhibitor and a β-adrenergic antagonist |
US5827835A (en) * | 1994-08-30 | 1998-10-27 | Alcon Laboratories, Inc. | Thermally-gelling emulsions |
US5618800A (en) * | 1994-08-30 | 1997-04-08 | Alcon Laboratories, Inc. | Thermally-gelling drug delivery vehicles containing cellulose ethers |
US5516808A (en) * | 1994-10-27 | 1996-05-14 | Sawaya; Assad S. | Topical cellulose pharmaceutical formulation |
US5603929A (en) * | 1994-11-16 | 1997-02-18 | Alcon Laboratories, Inc. | Preserved ophthalmic drug compositions containing polymeric quaternary ammonium compounds |
US6165490A (en) * | 1996-04-05 | 2000-12-26 | Staar Surgical Ag | Biological material, method of preparing such materials, uses thereof and products made therefrom |
US6172054B1 (en) | 1995-06-15 | 2001-01-09 | Alcon Laboratories, Inc. | Combination therapy for lowering and controlling intraocular pressure |
US5843470A (en) * | 1995-10-06 | 1998-12-01 | Mdv Technologies, Inc. | Method and composition for inhibiting post-surgical adhesions |
US6441047B2 (en) | 1995-11-17 | 2002-08-27 | Alcon Manufacturing Ltd.. | Combination therapy for treating glaucoma |
EP1057486A1 (en) * | 1995-11-17 | 2000-12-06 | Alcon Laboratories, Inc. | Use of drug combination for treating Glaucoma |
US6610292B2 (en) * | 1995-11-22 | 2003-08-26 | Ista Pharmaceuticals, Inc. | Use of hyaluronidase in the manufacture of an ophthalmic preparation for liquefying vitreous humor in the treatment of eye disorders |
US5866120A (en) * | 1995-11-22 | 1999-02-02 | Advanced Corneal Systems, Inc. | Method for accelerating clearance of hemorrhagic blood from the vitreous humor with hyaluronidase |
US5641532A (en) * | 1995-12-15 | 1997-06-24 | The Procter & Gamble Company | Beverages having stable flavor/cloud emulsions in the presence of polyphosphate-containing preservative systems by including gellan gum |
WO1997029777A1 (fr) | 1996-02-13 | 1997-08-21 | Dainippon Pharmaceutical Co., Ltd. | Systeme d'administration de medicament utilisant une galactoxyloglucane |
FR2754712B1 (fr) | 1996-10-17 | 1999-09-03 | Merck Sharp Dohme Chibret Lab | Compositions ophtalmiques |
US5888493A (en) * | 1996-12-05 | 1999-03-30 | Sawaya; Assad S. | Ophthalmic aqueous gel formulation and related methods |
EP0971641A4 (en) * | 1997-04-03 | 2003-08-13 | Point Biomedical Corp | SYSTEM FOR THE ADMINISTRATION OF AN INTRAVESICAL MEDICINAL PRODUCT |
GB9707934D0 (en) * | 1997-04-18 | 1997-06-04 | Danbiosyst Uk | Improved delivery of drugs to mucosal surfaces |
AU737442B2 (en) * | 1997-07-29 | 2001-08-16 | Alcon Laboratories, Inc. | Ophthalmic compositions containing galactomannan polymers and borate |
AU8570498A (en) | 1997-07-29 | 1999-02-22 | Alcon Laboratories, Inc. | Switchable viscoelastic systems containing galactomannan polymers and borate |
DE69826730T2 (de) * | 1997-07-29 | 2005-02-10 | Alcon Laboratories, Inc., Fort Worth | Konditionierungslösungen für die Pflege von harten Kontaktlinsen |
US20040063678A1 (en) * | 1997-10-06 | 2004-04-01 | Bausch & Lomb Incorporated | Dexamethasone Gel |
US6261547B1 (en) | 1998-04-07 | 2001-07-17 | Alcon Manufacturing, Ltd. | Gelling ophthalmic compositions containing xanthan gum |
US6174524B1 (en) | 1999-03-26 | 2001-01-16 | Alcon Laboratories, Inc. | Gelling ophthalmic compositions containing xanthan gum |
US6312666B1 (en) * | 1998-11-12 | 2001-11-06 | 3M Innovative Properties Company | Methods of whitening teeth |
US6312667B1 (en) * | 1998-11-12 | 2001-11-06 | 3M Innovative Properties Company | Methods of etching hard tissue in the oral environment |
US6669927B2 (en) | 1998-11-12 | 2003-12-30 | 3M Innovative Properties Company | Dental compositions |
EA004050B1 (ru) * | 1998-12-11 | 2003-12-25 | Бакулиш Мафатлал Хамар | Способ изготовления состава местных бета-блокаторов улучшенного действия |
EP1616869B1 (en) * | 1999-01-25 | 2012-04-04 | National Jewish Health | Substituted porphyrins and their therapeutic use |
ATE243038T1 (de) | 1999-11-01 | 2003-07-15 | Alcon Inc | Pharmazeutische zusammensetzungen ein fluorchinolonantibiotikum und xanthangummi enthaltend |
PE20020146A1 (es) * | 2000-07-13 | 2002-03-31 | Upjohn Co | Formulacion oftalmica que comprende un inhibidor de ciclooxigenasa-2 (cox-2) |
MXPA03000813A (es) | 2000-07-28 | 2005-08-16 | Alcon Inc | Composiciones farmaceuticas que contienen tobramicina y goma de xantano. |
US20030219461A1 (en) * | 2000-09-12 | 2003-11-27 | Britten Nancy J. | Parenteral combination therapy for infective conditions |
PE20020578A1 (es) | 2000-10-10 | 2002-08-14 | Upjohn Co | Una composicion de antibiotico topico para el tratamiento de infecciones oculares |
JP2002154989A (ja) * | 2000-11-14 | 2002-05-28 | Lion Corp | 眼科用組成物、及び生体粘膜への薬物の滞留性向上組成物 |
US20090258955A1 (en) * | 2000-12-20 | 2009-10-15 | Alcon, Inc. | Intraocular irrigating solution having improved flow characteristics |
WO2002049610A2 (en) * | 2000-12-20 | 2002-06-27 | Alcon, Inc. | Ophthalmic irrigating solution adapted for use in lasik surgery |
PT1343474E (pt) * | 2000-12-20 | 2010-04-19 | Alcon Inc | Solução de irrigação intra-ocular com características de fluidez aperfeiçoadas |
JP4169596B2 (ja) * | 2000-12-20 | 2008-10-22 | アルコン、インコーポレイテッド | 白内障を液化破壊により取り除くための溶液 |
US7084130B2 (en) * | 2001-12-11 | 2006-08-01 | Alcon, Inc. | Intraocular irrigating solution having improved flow characteristics |
AU2002232437A1 (en) * | 2000-12-20 | 2002-07-01 | Alcon Universal Ltd. | Ophthalmic lubricating solution adapted for use in lasik surgery |
US20040121947A1 (en) * | 2000-12-28 | 2004-06-24 | Oklahoma Medical Research Foundation | Compounds which inhibit beta-secretase activity and methods of use thereof |
US20020172712A1 (en) * | 2001-03-19 | 2002-11-21 | Alan Drizen | Antiemetic, anti-motion sustained release drug delivery system |
AU2002312194B8 (en) * | 2001-06-01 | 2008-05-15 | Aeolus Sciences, Inc. | Oxidant scavengers for treatment of diabetes or use in transplantation or induction of immune tolerance |
ATE404193T1 (de) * | 2001-06-05 | 2008-08-15 | Ronald Aung-Din | Topische migränetherapie |
US8329734B2 (en) * | 2009-07-27 | 2012-12-11 | Afgin Pharma Llc | Topical therapy for migraine |
US20080199524A1 (en) * | 2001-08-10 | 2008-08-21 | Toray Industries, Inc. | Eyedrops containing particulate agar |
EP1424081A4 (en) | 2001-08-10 | 2005-09-21 | Toray Industries | COMPOSITIONS CONTAINING POLYSACCHARIDE AND USE THEREOF |
US20030220376A1 (en) * | 2001-08-10 | 2003-11-27 | Pharmacia Corporation | Methods for treating carbonic anhydrase mediated disorders |
US20060234944A1 (en) * | 2001-10-23 | 2006-10-19 | Oklahoma Medical Reseach Foundation | Beta-secretase inhibitors and methods of use |
AU2002359301B2 (en) * | 2001-10-23 | 2008-07-03 | Comentis, Inc. | Beta-secretase inhibitors and methods of use |
US6620405B2 (en) | 2001-11-01 | 2003-09-16 | 3M Innovative Properties Company | Delivery of hydrogel compositions as a fine mist |
JP2005521690A (ja) * | 2002-02-22 | 2005-07-21 | ファルマシア・コーポレーション | ゴム系を含む眼科用製剤 |
US7666876B2 (en) * | 2002-03-19 | 2010-02-23 | Vernalis (R&D) Limited | Buprenorphine formulations for intranasal delivery |
US7030149B2 (en) * | 2002-04-19 | 2006-04-18 | Allergan, Inc. | Combination of brimonidine timolol for topical ophthalmic use |
US7642258B2 (en) * | 2002-04-19 | 2010-01-05 | Allergan, Inc. | Combination of brimonidine and timolol for topical ophthalmic use |
CA2484797A1 (en) * | 2002-05-06 | 2003-11-13 | Washington University | Methods of treatment of glaucoma and other conditions mediated by nos-2 expression via inhibition of the egfr pathway |
US20080153894A1 (en) * | 2002-12-19 | 2008-06-26 | Pharmacia Corporation | Cyclooxygenase-2 inhibitor and antibacterial agent combination for intramammary treatment of mastitis |
NZ540885A (en) * | 2002-12-20 | 2009-02-28 | Chakshu Res Inc | Ophthalmic formulation for the prevention and treatment of ocular conditions |
US20060172972A1 (en) * | 2002-12-20 | 2006-08-03 | Chakshu Research Inc | Formulation and method for administration of ophthalmologically active agents |
US20060177430A1 (en) * | 2002-12-20 | 2006-08-10 | Chakshu Research Inc | Treatment of ocular disorders with ophthalmic formulations containing methylsulfonylmethane as a transport enhancer |
US20060166879A1 (en) * | 2002-12-20 | 2006-07-27 | Chakshu Research Inc | Treatment of conditions associated with the presence of macromolecular aggregates, particularly ophthalmic disorders |
GB0300531D0 (en) * | 2003-01-10 | 2003-02-12 | West Pharm Serv Drug Res Ltd | Pharmaceutical compositions |
US20040191332A1 (en) * | 2003-03-27 | 2004-09-30 | Allergan, Inc. | Preserved ophthalmic compositions |
US20070065463A1 (en) * | 2003-06-20 | 2007-03-22 | Ronald Aung-Din | Topical therapy for the treatment of migranes, muscle sprains, muscle spasms, spasticity and related conditions |
CN1878571B (zh) * | 2003-11-10 | 2010-09-08 | 东丽株式会社 | 含有多糖类的组合物及泪液层稳定化滴眼剂 |
US20050129770A1 (en) * | 2003-12-11 | 2005-06-16 | Alcon, Inc. | Ophthalmic compositions containing a PVA/borate gelling system |
WO2005060933A1 (en) * | 2003-12-11 | 2005-07-07 | Alcon, Inc. | Ophthalmic compositions containing a polysaccharide/borate gelling system |
JP4771044B2 (ja) * | 2004-09-15 | 2011-09-14 | 大正製薬株式会社 | 粘膜適用液剤 |
US20080207527A1 (en) * | 2004-09-17 | 2008-08-28 | Comentis, Inc. | Bicyclic Compounds Which Inhibit Beta-Secretase Activity and Methods of Use Thereof |
EP1799660A2 (en) * | 2004-09-17 | 2007-06-27 | Comentis, Inc. | Amino-containing compounds which inhibit memapsin 2 beta-secretase activity and methods of use thereof |
US20080096859A1 (en) * | 2004-10-01 | 2008-04-24 | Sullivan Kathleen A | Compositions and Methods for Treating Ophthalmic Diseases |
US9512125B2 (en) | 2004-11-19 | 2016-12-06 | The Regents Of The University Of California | Substituted pyrazolo[3.4-D] pyrimidines as anti-inflammatory agents |
US20070059274A1 (en) * | 2004-12-01 | 2007-03-15 | Bahram Asgharian | Ophthalmic compositions containing a PVA/borate gelling system |
WO2006083927A2 (en) * | 2005-01-31 | 2006-08-10 | Coram Bioscience, Inc. | Antimicrobial agent |
KR20080015079A (ko) * | 2005-04-08 | 2008-02-18 | 코멘티스, 인코포레이티드 | 베타 세크레타제 활성을 억제하는 화합물 및 이것의 사용방법 |
AU2006270094A1 (en) * | 2005-07-15 | 2007-01-25 | Chakshu Research Inc. | Prevention and treatment of ophthalmic complications of diabetes |
US7534795B2 (en) * | 2005-10-25 | 2009-05-19 | Allergan, Inc. | Compounds and their use related to compositions for treating disease |
NZ568694A (en) | 2005-11-09 | 2011-09-30 | Zalicus Inc | Method, compositions, and kits for the treatment of medical conditions |
CA2633655A1 (en) * | 2005-12-19 | 2007-07-05 | Comentis, Inc. | Topical mecamylamine formulations for ocular administration and uses therof |
TW200808375A (en) | 2006-05-12 | 2008-02-16 | Otsuka Pharma Co Ltd | Hydrogel suspension and manufacturing process thereof |
KR100802534B1 (ko) | 2006-06-13 | 2008-02-14 | 주식회사태준제약 | 저자극성 점안제 조성물 및 이의 제조 방법 |
WO2008005457A2 (en) | 2006-06-30 | 2008-01-10 | Sunesis Pharmaceuticals | Pyridinonyl pdk1 inhibitors |
HUE043228T2 (hu) | 2007-06-22 | 2019-08-28 | Univ Texas | Stabil szubmikron peptid vagy protein részecskék képzése vékonyfilm fagyasztással |
EP2178837A2 (en) * | 2007-07-26 | 2010-04-28 | Comentis, Inc. | Isophthalamide derivatives inhibiting beta-secretase activity |
MX2010002938A (es) * | 2007-09-24 | 2010-04-01 | Comentis Inc | Derivados de (3-hidroxi-4-amino-butan-2-il)-3-(2-tiazol-2-il-pirro lidin-1-carbonil)benzamida y compuestos relacionados como inhibidores de beta-secretasa para tratar enfermedad de alzheimer. |
MX2010009857A (es) * | 2008-03-07 | 2010-12-07 | Sun Pharma Advanced Res Co Ltd | Composicion oftalmica. |
CA2725012C (en) | 2008-05-23 | 2019-05-07 | National Jewish Health | Methods for treating injury associated with exposure to an alkylating species |
WO2010005507A1 (en) | 2008-06-30 | 2010-01-14 | Afgin Pharma, Llc | Topical regional neuro-affective therapy |
WO2010006072A2 (en) | 2008-07-08 | 2010-01-14 | The Regents Of The University Of California | Mtor modulators and uses thereof |
WO2010011684A2 (en) * | 2008-07-21 | 2010-01-28 | The Regents Of The University Of California | Prodrug and fluoregenic compositions and methods for using the same |
WO2010031056A2 (en) | 2008-09-15 | 2010-03-18 | The Regents Of The University Of California | Methods and compositions for modulating ire1, src, and abl activity |
JP2010132587A (ja) * | 2008-12-03 | 2010-06-17 | Teika Seiyaku Kk | 眼科用剤 |
US8580947B2 (en) | 2009-02-05 | 2013-11-12 | Gene Signal International Sa | Pharmaceutical composition for preventing, stabilising and/or inhibiting blood and lymph vascularization |
US8470997B2 (en) * | 2009-02-05 | 2013-06-25 | Gene Signal International Sa | Pharmaceutical composition for preventing, stabilising and/or inhibiting blood and lymph vascularization |
RU2482851C2 (ru) * | 2009-02-20 | 2013-05-27 | Микро Лабс Лимитед | Хранение стабильного продукта простагландина |
MX353747B (es) | 2009-08-17 | 2018-01-26 | Memorial Sloan Kettering Cancer Center Star | Compuesto de union a proteina de choque termico, composiciones, y metodos para producir y usar los mismos. |
WO2011029043A1 (en) | 2009-09-04 | 2011-03-10 | Biogen Idec Ma Inc. | Heteroaryl btk inhibitors |
CA2771822C (en) | 2009-09-04 | 2020-08-11 | Daniel A. Erlanson | Bruton's tyrosine kinase inhibitors |
US8679511B2 (en) * | 2009-10-01 | 2014-03-25 | Duquesne University of the Holy Spririt | In-situ gel ophthalmic drug delivery system of estradiol or other estrogen for prevention of cataracts |
CN102665718B (zh) | 2009-10-06 | 2016-03-09 | 米伦纽姆医药公司 | 可用作pdk1抑制剂的杂环化合物 |
US8980899B2 (en) | 2009-10-16 | 2015-03-17 | The Regents Of The University Of California | Methods of inhibiting Ire1 |
PT2853262T (pt) | 2009-10-26 | 2017-01-31 | Sephoris Pharmaceuticals Llc | Tratamento de queimaduras solares usando analgésicos e anti-histamínicos |
CA2781056A1 (en) | 2009-11-16 | 2011-05-19 | Rebecca Maglathlin | Kinase inhibitors |
WO2011072257A2 (en) | 2009-12-10 | 2011-06-16 | The Regents Of The University Of California | Amyloid binding agents |
US9522153B2 (en) | 2009-12-22 | 2016-12-20 | Allergan, Inc. | Compositions and methods for lowering intraocular pressure |
DE102010009475B4 (de) | 2010-02-26 | 2011-11-24 | F. Holzer Gmbh | Verfahren zur Herstellung eines dosierbaren applikationsfertigen Präparates |
CA2829790C (en) | 2010-03-30 | 2018-06-05 | Verseon Corporation | Multisubstituted aromatic compounds as inhibitors of thrombin |
JP2013523828A (ja) | 2010-04-07 | 2013-06-17 | アラーガン インコーポレイテッド | 眼科用組成物のための保存剤の組み合わせ |
US20110250294A1 (en) | 2010-04-07 | 2011-10-13 | Allergan, Inc. | Combinations of preservative compositions for ophthalmic formulations |
JP5713791B2 (ja) * | 2010-05-12 | 2015-05-07 | テイカ製薬株式会社 | 眼科用剤 |
US20130149394A1 (en) | 2010-08-27 | 2013-06-13 | Wakamoto Pharmaceutical Co., Ltd. | Aqueous ophthalmic composition |
US8530449B2 (en) | 2010-09-09 | 2013-09-10 | Assad S. Sawaya | Composition for a topical ophthalmic clear colloidal liquid which undergoes a liquid-gel phase transition in the eye |
SG10201507554RA (en) | 2010-09-13 | 2015-10-29 | Bev Rx Inc | Aqueous drug delivery system comprising off - flavor masking agent |
WO2012058645A1 (en) | 2010-10-29 | 2012-05-03 | Biogen Idec Ma Inc. | Heterocyclic tyrosine kinase inhibitors |
JP5885271B2 (ja) | 2011-02-14 | 2016-03-15 | アラーガン、インコーポレイテッドAllergan,Incorporated | ビマトプロストのエステル誘導体の組成物および方法 |
US9376438B2 (en) | 2011-05-17 | 2016-06-28 | Principia Biopharma, Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
PL2710005T3 (pl) | 2011-05-17 | 2017-07-31 | Principia Biopharma Inc. | Inhibitory kinazy tyrozynowej |
JP6068451B2 (ja) | 2011-05-17 | 2017-01-25 | ザ・リージエンツ・オブ・ザ・ユニバーシテイ・オブ・カリフオルニア | キナーゼ阻害剤 |
US20140221282A1 (en) | 2011-05-25 | 2014-08-07 | Astrazeneca Pharmaceuticals Lp | Long duration dual hormone conjugates |
AU2012279154A1 (en) | 2011-07-01 | 2014-02-20 | The Regents Of The University Of California | Herpes virus vaccine and methods of use |
EP2751112B1 (en) | 2011-09-02 | 2019-10-09 | The Regents of The University of California | Substituted pyrazolo[3,4-d]pyrimidines and uses thereof |
CA2853729A1 (en) | 2011-10-28 | 2013-05-02 | Board Of Regents, The University Of Texas System | Novel compositions and methods for treating cancer |
EP2836482B1 (en) | 2012-04-10 | 2019-12-25 | The Regents of The University of California | Compositions and methods for treating cancer |
AR091273A1 (es) | 2012-06-08 | 2015-01-21 | Biogen Idec Inc | Inhibidores de pirimidinil tirosina quinasa |
EP2858500A4 (en) | 2012-06-08 | 2016-04-06 | Biogen Ma Inc | INHIBITORS OF BRUTON TYROSINE KINASE |
CA2913736A1 (en) | 2012-06-11 | 2013-12-19 | The Regents Of The University Of California | Compounds and methods of treating cancer |
US9090595B2 (en) | 2012-08-27 | 2015-07-28 | Allergan, Inc. | Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes |
EP2888239B1 (en) | 2012-08-27 | 2018-11-28 | Allergan, Inc. | Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes |
SI2892900T1 (en) | 2012-09-10 | 2018-01-31 | Principia Biopharma Inc. | Compounds of pyrazolopyrimidine, as kinase inhibitors |
BR112015006828A8 (pt) | 2012-09-26 | 2019-09-17 | Univ California | composto, ou um sal farmaceuticamente aceitável do mesmo; composição farmacêutica; uso do composto; e método para modular a atividade de uma proteína ire1 |
EP2909214B1 (en) | 2012-10-22 | 2020-07-22 | City of Hope | Etp derivatives |
US9364462B2 (en) | 2012-10-30 | 2016-06-14 | The Regents Of The University Of California | Alpha-1-adrenergic receptor agonist therapy |
EP2953950B1 (en) | 2013-02-11 | 2021-01-13 | The Regents of The University of California | Compositions and methods for treating neurodegenerative diseases |
WO2014143592A1 (en) | 2013-03-12 | 2014-09-18 | Allergan, Inc. | Inhibition of neovascularization by inhibition of prostanoid ip receptors |
EP2968296B1 (en) | 2013-03-12 | 2020-09-02 | The Regents of the University of California | Gamma-secretase modulators |
US9295665B2 (en) | 2013-03-12 | 2016-03-29 | Allergan, Inc. | Inhibition of neovascularization by simultaneous inhibition of prostanoid IP and EP4 receptors |
ES2877898T3 (es) | 2013-03-14 | 2021-11-17 | Univ California | Agentes mucolíticos de tiosacáridos |
AU2014236370C1 (en) | 2013-03-14 | 2019-01-17 | City Of Hope | 5-bromo-indirubins |
EP2968270A4 (en) | 2013-03-14 | 2016-08-17 | Univ California | MODULATION OF K2P CHANNELS |
BR112015023214A8 (pt) | 2013-03-15 | 2019-12-24 | Verseon Corp | composto, composição farmacêutica, e, uso de um composto ou composição farmacêutica |
BR112015023705A8 (pt) | 2013-03-15 | 2020-03-17 | Univ California | compostos, composições farmacêuticas, usos de um composto, e método para síntese do composto da fórmula (ia) |
BR112015021859A2 (pt) | 2013-03-15 | 2017-07-18 | Allergan Inc | bimatoprost para potencialização da produção de leptina |
CA2904794C (en) | 2013-03-15 | 2021-11-23 | Peter Walter | Modulators of the eif2alpha pathway |
JP6397479B2 (ja) | 2013-03-15 | 2018-09-26 | エータイアー ファーマ, インコーポレイテッド | ヒスチジル−tRNAシンテターゼFcコンジュゲート |
US9227978B2 (en) | 2013-03-15 | 2016-01-05 | Araxes Pharma Llc | Covalent inhibitors of Kras G12C |
WO2014146111A2 (en) | 2013-03-15 | 2014-09-18 | The Regents Of The University Of California | Analgesic compounds and methods of use |
SG10201707480PA (en) | 2013-03-15 | 2017-10-30 | Verseon Corp | Multisubstituted aromatic compounds as serine protease inhibitors |
US8957080B2 (en) | 2013-04-09 | 2015-02-17 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
WO2014190207A1 (en) | 2013-05-22 | 2014-11-27 | The Regents Of The University Of California | Aurora kinase inhibitors |
US9795691B2 (en) | 2013-06-24 | 2017-10-24 | City Of Hope | Chemically-linked nanoparticles |
CA2917527C (en) | 2013-07-15 | 2022-06-14 | Board Of Regents, The University Of Texas System | Compounds and methods for treating cancer, neurological disorders, ethanol withdrawal, anxiety, depression, and neuropathic pain |
HUE053282T2 (hu) | 2013-08-19 | 2021-06-28 | Univ California | Vegyületek és eljárások epilepsziás rendellenesség kezelésére |
WO2015026935A2 (en) | 2013-08-20 | 2015-02-26 | City Of Hope | Hdac8 inhibitors for treating cancer |
WO2015031799A1 (en) | 2013-08-30 | 2015-03-05 | The Regents Of The University Of California, A California Corporation | Scintillator nanocrystal-containing compositions and methods for their use |
JO3805B1 (ar) | 2013-10-10 | 2021-01-31 | Araxes Pharma Llc | مثبطات كراس جي12سي |
MY179781A (en) | 2013-12-11 | 2020-11-13 | Biogen Ma Inc | Biaryl inhibitors of bruton's tyrosine kinase |
US10280169B2 (en) | 2013-12-11 | 2019-05-07 | Biogen Ma Inc. | Biaryl bruton's tyrosine kinase inhibitors |
CN106456645B (zh) | 2013-12-23 | 2021-03-23 | 纪念斯隆-凯特琳癌症中心 | 用于放射性标记的方法和试剂 |
EP3091985A4 (en) | 2014-01-10 | 2017-11-29 | Manistee Partners LLC | Treatment of migraines |
WO2015116856A2 (en) | 2014-01-29 | 2015-08-06 | City Of Hope | Farnesoid x receptor antagonists |
HRP20220759T1 (hr) | 2014-02-11 | 2022-09-02 | Mitokinin, Inc. | Pripravci i postupci koji ih koriste za liječenje neurodegenerativne i mitohondrijske bolesti |
CA2937752C (en) | 2014-02-14 | 2023-02-07 | The Regents Of The University Of California | Cyclic peroxides as prodrugs for selective delivery of agents |
AU2015259752B2 (en) | 2014-02-20 | 2019-06-20 | Allergan, Inc. | Reduced central corneal thickening by use of hydrophilic ester prodrugs of beta-chlorocyclopentanes |
CA2939186C (en) | 2014-02-21 | 2023-03-07 | Principia Biopharma Inc. | Salts and solid form of a btk inhibitor |
US20150259288A1 (en) | 2014-03-14 | 2015-09-17 | City Of Hope | 5-bromo-indirubins |
AU2015235929B2 (en) | 2014-03-26 | 2019-02-14 | City Of Hope | Treatment of BRCA1-defective cancer or resistant cancers |
EP3129354B1 (en) | 2014-04-07 | 2022-01-05 | The Regents of the University of California | Inhibitors of fatty acid amide hydrolase (faah) enzyme with improved oral bioavailability and their use as medicaments |
BR112016026470A8 (pt) | 2014-05-13 | 2021-07-20 | Memorial Sloan Kettering Cancer Center | composto modulador de hsp70, composição farmacêutica que o compreende e uso do referido composto |
US10166246B2 (en) | 2014-05-27 | 2019-01-01 | City Of Hope | TGR5 agonist complexes for treating diabetes and cancer |
US9012402B1 (en) | 2014-06-11 | 2015-04-21 | James Blanchard | Gel for topical delivery of NSAIDs to provide relief of musculoskeletal pain and methods for its preparation |
US10414814B2 (en) | 2014-07-03 | 2019-09-17 | City Of Hope | Tumor-selective CTLA-4 antagonists |
US11072681B2 (en) | 2014-07-28 | 2021-07-27 | The Regents Of The University Of California | Compositions and methods of making polymerizing nucleic acids |
WO2016023036A1 (en) | 2014-08-08 | 2016-02-11 | The Regents Of The University Of California | High density peptide polymers |
CA2960992A1 (en) | 2014-09-11 | 2016-03-17 | The Regents Of The University Of California | Mtorc1 inhibitors |
KR20230145550A (ko) | 2014-09-15 | 2023-10-17 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 뉴클레오타이드 유사체 |
BR112017004704A2 (pt) | 2014-09-17 | 2018-01-23 | Verseon Corp | composto, composição farmacêutica, e, método para tratar uma doença ou distúrbio em um indivíduo |
JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
WO2016049524A1 (en) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
WO2016049568A1 (en) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Methods and compositions for inhibition of ras |
CN111978310A (zh) | 2014-10-02 | 2020-11-24 | 阿勒根公司 | γ-内酰胺的酯前药及其用途 |
WO2016061147A1 (en) | 2014-10-13 | 2016-04-21 | John Eric Paderi | Luminal vessel coating for arteriovenous fistula |
WO2016061145A1 (en) | 2014-10-13 | 2016-04-21 | Symic Biomedical, Inc. | Synthetic proteoglycans for preventing tissue adhesion |
WO2016065083A1 (en) | 2014-10-21 | 2016-04-28 | Symic Biomedical, Inc. | Peptidoglycans comprising collagen-binding peptides for treating gastroesophageal injury |
WO2016100914A1 (en) | 2014-12-18 | 2016-06-23 | Gourlay Steven | Treatment of pemphigus |
US10689423B2 (en) | 2015-01-13 | 2020-06-23 | City Of Hope | CTLA4-binding protein peptide-linker masks |
CN113797349A (zh) | 2015-01-16 | 2021-12-17 | 希望之城 | 细胞穿透抗体 |
US10227333B2 (en) | 2015-02-11 | 2019-03-12 | Curtana Pharmaceuticals, Inc. | Inhibition of OLIG2 activity |
EA201992474A3 (ru) | 2015-02-25 | 2020-05-31 | Дзе Риджентс Оф Дзе Юниверсити Оф Калифорниа | Агонисты 5ht для лечения нарушений |
AU2016224975B2 (en) | 2015-02-27 | 2020-10-22 | The Regents Of The University Of California | Small molecules that enable cartilage rejuvanation |
LT3261639T (lt) | 2015-02-27 | 2022-11-25 | Verseon International Corporation | Pakaitiniai pirazolo junginiai kaip serino proteazės inhibitoriai |
CA2977521C (en) | 2015-02-27 | 2024-03-19 | Curtana Pharmaceuticals, Inc. | 1-(aryl)-3-(heteroaryl) urea compounds and their use as olig2 inhibitors |
US10383816B2 (en) | 2015-03-02 | 2019-08-20 | Afgin Pharma, Llc | Topical regional neuro-affective therapy with cannabinoid combination products |
US10716766B2 (en) | 2015-03-02 | 2020-07-21 | Afgin Pharma, Llc | Topical regional neuro-affective therapy with cannabinoids |
CA2981504C (en) | 2015-03-30 | 2023-10-24 | City Of Hope | Mechanically interlocking complexes |
BR112017021869A2 (pt) | 2015-04-10 | 2018-12-11 | Araxes Pharma Llc | compostos quinazolina substituídos e métodos de uso dos mesmos |
MX2017013275A (es) | 2015-04-15 | 2018-01-26 | Araxes Pharma Llc | Inhibidores triciclicos fusionados de kras y metodos de uso de los mismos. |
WO2016166604A1 (en) | 2015-04-17 | 2016-10-20 | Ludwig Institute For Cancer Research Ltd | Plk4 inhibitors |
EP3286214B1 (en) | 2015-04-24 | 2023-12-06 | The Regents of the University of California | Modulators of ror1-ror2 binding |
CN114990141A (zh) | 2015-05-15 | 2022-09-02 | 希望之城 | 嵌合抗原受体组合物 |
US10787664B2 (en) | 2015-05-26 | 2020-09-29 | City Of Hope | Compounds of chemically modified oligonucleotides and methods of use thereof |
US10765696B2 (en) | 2015-06-10 | 2020-09-08 | City Of Hope | Compositions of and methods of treatment with zwitterionic polysaccharide |
US20180282310A1 (en) | 2015-06-10 | 2018-10-04 | Biogen Ma Inc. | Forms and compositions of biaryl inhibitors of bruton's tyrosine kinase |
TW201718572A (zh) | 2015-06-24 | 2017-06-01 | 普林斯匹亞生物製藥公司 | 酪胺酸激酶抑制劑 |
CA2991052A1 (en) | 2015-07-02 | 2017-01-05 | City Of Hope | Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof |
US10144724B2 (en) | 2015-07-22 | 2018-12-04 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
WO2017024238A1 (en) | 2015-08-06 | 2017-02-09 | City Of Hope | Cell penetrating protein-antibody conjugates and methods of use |
EP3128007A1 (en) | 2015-08-07 | 2017-02-08 | Gene Signal International SA | Sterile emulsion comprising a stable phosphorothioate oligonucleotide |
US11136301B2 (en) | 2015-08-31 | 2021-10-05 | The Regents of the University of California, A California Corporation et al. | Broad spectrum antiviral compounds and uses thereof |
US11124483B2 (en) | 2015-09-02 | 2021-09-21 | The Regents Of The University Of California | HER3 ligands and uses thereof |
JP6933644B2 (ja) | 2015-09-04 | 2021-09-08 | シティ・オブ・ホープCity of Hope | アンドロゲン受容体拮抗薬 |
WO2017051251A1 (en) | 2015-09-25 | 2017-03-30 | Ludwig Institute For Cancer Research Ltd | 3-hydroxy-quinazoline-2,4-dione derivatives and their use as nuclease modulators |
EP3356354A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
WO2017058792A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
WO2017058807A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
EP3356349A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
US10647703B2 (en) | 2015-09-28 | 2020-05-12 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
US10689356B2 (en) | 2015-09-28 | 2020-06-23 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
WO2017058728A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
TW201718028A (zh) | 2015-10-13 | 2017-06-01 | 賽米克Ip有限責任公司 | Ve-鈣黏蛋白結合性生物結合物 |
US10801026B2 (en) | 2015-10-15 | 2020-10-13 | City Of Hope | Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof |
JP2018533939A (ja) | 2015-10-19 | 2018-11-22 | アラクセス ファーマ エルエルシー | Rasの阻害剤をスクリーニングするための方法 |
BR112018008025A2 (pt) | 2015-10-23 | 2018-10-23 | Sunesis Pharmaceuticals, Inc. | inibidores de pdk1 heterocíclicos para uso no trata-mento de câncer |
BR112018008103A2 (pt) | 2015-10-23 | 2018-11-06 | Erx Pharmaceuticals, Inc. | análogos de celastrol |
US11058700B2 (en) | 2015-10-28 | 2021-07-13 | City Of Hope | Macrocyclic lactones and uses thereof as modulators of purinergic receptors |
KR20180081596A (ko) | 2015-11-16 | 2018-07-16 | 아락세스 파마 엘엘씨 | 치환된 헤테로사이클릭 그룹을 포함하는 2-치환된 퀴나졸린 화합물 및 이의 사용 방법 |
US9988357B2 (en) | 2015-12-09 | 2018-06-05 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
US20190119259A1 (en) | 2015-12-10 | 2019-04-25 | City Of Hope | Cell penetrating cyanine-coupled antibodies |
DK3394046T3 (da) | 2015-12-24 | 2022-04-04 | Univ California | Cftr-regulatorer og fremgangsmåder til anvendelse deraf |
ES2909316T3 (es) | 2015-12-24 | 2022-05-06 | Univ California | Reguladores de CFTR y métodos de uso de los mismos |
JP6931002B2 (ja) | 2016-01-05 | 2021-09-01 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | ベンゾチアゾール両親媒性物質 |
US10519442B2 (en) | 2016-02-11 | 2019-12-31 | City Of Hope | Twist signaling inhibitor compositions and methods of using the same |
WO2017161344A1 (en) | 2016-03-17 | 2017-09-21 | The Regants Of The University Of California | Compositions and methods for treating parasitic diseases |
US10822312B2 (en) | 2016-03-30 | 2020-11-03 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use |
GR1009006B (el) | 2016-04-01 | 2017-04-04 | Φαρματεν Ανωνυμος Βιομηχανικη Και Εμπορικη Εταιρεια Φαρμακευτικων Ιατρικων Και Καλλυντικων Προϊοντων | Φαρμακευτικο σκευασμα ελευθερο συντηρητικου για οφθαλμικη χρηση περιεχον βιματοπροστη και τιμολολη |
GR1009040B (el) | 2016-04-19 | 2017-05-19 | Φαρματεν Ανωνυμος Βιομηχανικη Και Εμπορικη Εταιρεια Φαρμακευτικων Ιατρικων Και Καλλυντικων Προϊοντων | Φαρμακευτικο οφθαλμικο σκευασμα ελευθερο συντηρητικου |
PT3458448T (pt) | 2016-04-25 | 2021-09-10 | Forma Therapeutics Inc | Inibidores fasn para uso no tratamento de esteato-hepatite não-alcoólica |
US20210323913A1 (en) | 2016-04-29 | 2021-10-21 | Board Of Regents, The University Of Texas System | Sigma receptor binders |
TWI763668B (zh) | 2016-05-05 | 2022-05-11 | 美商嘉來克生命科學有限責任公司 | 整合應激途徑之調節劑 |
TW201808914A (zh) | 2016-05-05 | 2018-03-16 | 嘉來克生命科學有限責任公司 | 整合應激途徑之調節劑 |
KR102243775B1 (ko) | 2016-05-12 | 2021-04-22 | 아나코르 파마슈티칼스 인코포레이티드 | 옥사보롤 에스터 및 이의 용도 |
US10918648B2 (en) | 2016-05-26 | 2021-02-16 | The Regents Of The University Of California | Estrogen receptor modulator combinations |
CA3028169A1 (en) | 2016-06-29 | 2018-01-04 | Principia Biopharma Inc. | Modified release formulations of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
WO2018013609A2 (en) | 2016-07-11 | 2018-01-18 | The Regents The University Of California | Synthetic melanin nanoparticles uses thereof |
US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
JP7214632B2 (ja) | 2016-07-21 | 2023-01-30 | バイオジェン エムエー インク. | ブルトン型チロシンキナーゼ阻害剤のコハク酸塩形態および組成物 |
US10179787B2 (en) | 2016-07-29 | 2019-01-15 | Flx Bio, Inc. | Chemokine receptor modulators and uses thereof |
US20180049994A1 (en) | 2016-08-16 | 2018-02-22 | Afgin Pharma, Llc | Topical regional neuro-affective therapy with caryophyllene |
US11542261B2 (en) | 2016-08-17 | 2023-01-03 | Children's Hospital Medical Center | Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors |
US11254667B2 (en) | 2016-08-17 | 2022-02-22 | Children's Hospital Medical Center | Substituted imidazo[1,2-A]pyridines as IRAK 1/4 and flt3 inhibitors |
WO2018039612A1 (en) | 2016-08-26 | 2018-03-01 | The Regents Of The University Of California | Compositions and methods for promoting hair growth with mpc1 inhibitors |
EP3512565A4 (en) | 2016-09-13 | 2020-05-06 | The Jackson Laboratory | DEMETHYLATION AND METHYLATION OF TARGETED DNA |
EP3512520B1 (en) | 2016-09-15 | 2023-06-21 | City of Hope | Dithio derivatives of epidithiodiketopiperazine (etp) |
US10849955B2 (en) | 2016-09-28 | 2020-12-01 | City Of Hope | Methods of treating pancreatic cancer using GPCR antagonists |
US10280172B2 (en) | 2016-09-29 | 2019-05-07 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
CN110312711A (zh) | 2016-10-07 | 2019-10-08 | 亚瑞克西斯制药公司 | 作为ras抑制剂的杂环化合物及其使用方法 |
US10646540B2 (en) | 2016-11-18 | 2020-05-12 | City Of Hope | Peptide inhibitors of twist |
WO2018112420A1 (en) | 2016-12-15 | 2018-06-21 | The Regents Of The University Of California | Compositions and methods for treating cancer |
WO2018140599A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | Benzothiophene and benzothiazole compounds and methods of use thereof |
WO2018140514A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds as kras g12c inhibitors for the treatment of cancer |
EP3573971A1 (en) | 2017-01-26 | 2019-12-04 | Araxes Pharma LLC | 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer |
EP3573967A1 (en) | 2017-01-26 | 2019-12-04 | Araxes Pharma LLC | Fused hetero-hetero bicyclic compounds and methods of use thereof |
EP3573954A1 (en) | 2017-01-26 | 2019-12-04 | Araxes Pharma LLC | Fused bicyclic benzoheteroaromatic compounds and methods of use thereof |
US10052343B1 (en) | 2017-02-03 | 2018-08-21 | Gene Signal International Sa | Sterile formulation comprising a stable phosphorothioate oligonucleotide |
EP3576753B1 (en) | 2017-02-03 | 2024-04-17 | Laboratoires KÔL | Sterile emulsion comprising a stable phosphorothioate oligonucleotide |
CN110869357A (zh) | 2017-05-25 | 2020-03-06 | 亚瑞克西斯制药公司 | 化合物及其用于治疗癌症的使用方法 |
WO2018218070A2 (en) | 2017-05-25 | 2018-11-29 | Araxes Pharma Llc | Covalent inhibitors of kras |
WO2018218069A1 (en) | 2017-05-25 | 2018-11-29 | Araxes Pharma Llc | Quinazoline derivatives as modulators of mutant kras, hras or nras |
US11414419B2 (en) | 2017-06-21 | 2022-08-16 | Mitokinin, Inc. | Substituted purines for the treatment of neurodegenerative and mitochondrial diseases |
WO2019006371A1 (en) | 2017-06-30 | 2019-01-03 | City Of Hope | COMPOSITIONS AND METHODS FOR MODULATING MACROPHAGE ACTIVITY |
US10821075B1 (en) | 2017-07-12 | 2020-11-03 | James Blanchard | Compositions for topical application of a medicaments onto a mammalian body surface |
US11389460B2 (en) | 2017-09-15 | 2022-07-19 | City Of Hope | Methods and compositions for treating endometrial cancer |
EP3688028A2 (en) | 2017-09-29 | 2020-08-05 | Genentech, Inc. | Peptide antibiotic complexes and methods of use thereof |
US20200354452A1 (en) | 2017-09-29 | 2020-11-12 | City Of Hope | Cars and bispecific antibodies for treatment of mantle cell lymphoma |
US11260048B2 (en) | 2017-10-03 | 2022-03-01 | The Schepens Eye Research Institute, Inc. | Compounds and compositions for inhibiting retinal pigment epithelium degeneration and methods using the same |
JP2020536920A (ja) | 2017-10-10 | 2020-12-17 | サイロス ファーマシューティカルズ, インコーポレイテッド | ピロロトリアジン化合物およびtamキナーゼを阻害する方法 |
WO2019079819A1 (en) | 2017-10-20 | 2019-04-25 | City Of Hope | COMPOSITION AND METHOD FOR ACTIVATION OF LATENT HUMAN IMMUNODEFICIENCY VIRUS (HIV) |
UY37956A (es) | 2017-11-02 | 2019-05-31 | Abbvie Inc | Moduladores de la vía de estrés integrada |
UY37957A (es) | 2017-11-02 | 2019-05-31 | Abbvie Inc | Moduladores de la vía de estrés integrada |
UY37958A (es) | 2017-11-02 | 2019-05-31 | Abbvie Inc | Moduladores de la vía de estrés integrada |
BR112020008834A2 (pt) | 2017-11-02 | 2020-12-22 | Calico Life Sciences Llc | Moduladores da via de estresse integrada |
CA3080959A1 (en) | 2017-11-02 | 2019-05-09 | Calico Life Sciences Llc | Modulators of the integrated stress pathway |
EP3704098B1 (en) | 2017-11-02 | 2024-01-24 | Calico Life Sciences LLC | Modulators of the integrated stress pathway |
JP7307057B2 (ja) | 2017-11-02 | 2023-07-11 | カリコ ライフ サイエンシーズ エルエルシー | 統合的ストレス経路の調節剤 |
MX2020004538A (es) | 2017-11-02 | 2020-09-18 | Calico Life Sciences Llc | Moduladores de la vía de estrés integrada. |
AU2018358157B2 (en) | 2017-11-02 | 2023-03-09 | Abbvie Inc. | Modulators of the integrated stress pathway |
RU2020118594A (ru) | 2017-11-06 | 2021-12-09 | Рапт Терапьютикс, Инк. | Противораковые агенты |
CN111698989B (zh) | 2017-12-07 | 2023-08-01 | 安普利克斯制药公司 | 杂环取代的吡啶衍生物抗真菌剂 |
WO2019126037A1 (en) | 2017-12-19 | 2019-06-27 | City Of Hope | Modified tracrrnas grnas, and uses thereof |
EP3740206B1 (en) | 2018-01-16 | 2024-03-06 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2019143719A1 (en) | 2018-01-16 | 2019-07-25 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
IL276295B2 (en) | 2018-01-26 | 2024-02-01 | Rapt Therapeutics Inc | Modulators of chemokine receptors and their uses |
EP3765459A1 (en) | 2018-03-13 | 2021-01-20 | Shire Human Genetic Therapies, Inc. | Substituted imidazopyridines as inhibitors of plasma kallikrein and uses thereof |
EP3784233A4 (en) | 2018-04-27 | 2022-03-02 | Spruce Biosciences, Inc. | METHODS OF TREATMENT OF TESTIC AND OVARIAN ADRENAL TUMORS |
CA3098698A1 (en) | 2018-05-01 | 2019-11-07 | Revolution Medicines, Inc. | C26-linked rapamycin analogs as mtor inhibitors |
US20190336609A1 (en) | 2018-05-01 | 2019-11-07 | Revolution Medicines, Inc. | C40-, C28-, and C-32-Linked Rapamycin Analogs as mTOR Inhibitors |
US11931345B2 (en) | 2018-05-04 | 2024-03-19 | Cirius Therapeutics, Inc. | Thiazolidinedione analogs for the treatment of NAFLD and metabolic diseases |
WO2019236631A1 (en) | 2018-06-05 | 2019-12-12 | Rapt Therapeutics, Inc. | Pyrazolo-pyrimidin-amino-cycloalkyl compounds and their therapeutic uses |
KR102533477B1 (ko) | 2018-06-21 | 2023-05-18 | 칼리코 라이프 사이언시스 엘엘씨 | 단백질 타이로신 포스파타아제 억제제 및 그의 사용 방법 |
JP2021530445A (ja) | 2018-06-25 | 2021-11-11 | アンプリックス ファーマシューティカルズ,インク. | 複素環およびアミノ基によって置換されたピリジン誘導体 |
CN112867503A (zh) | 2018-08-24 | 2021-05-28 | 希望之城 | 掩蔽的细胞因子缀合物 |
TWI771621B (zh) | 2018-10-11 | 2022-07-21 | 美商嘉來克生命科學有限責任公司 | 整合應激路徑之前藥調節劑 |
EP3856742A4 (en) | 2018-11-01 | 2022-06-22 | Lynk Pharmaceuticals Co. Ltd. | TRICYCLIC JANUS KINASE 1 INHIBITORS, AND RELATED COMPOSITIONS AND METHODS |
CN113242734A (zh) * | 2018-11-26 | 2021-08-10 | 艾葳生物科技有限公司 | 用于药物递送的药用生物可溶凝胶 |
JP7204005B2 (ja) | 2019-03-14 | 2023-01-13 | カリコ ライフ サイエンシーズ エルエルシー | タンパク質チロシンホスファターゼ阻害物質及びその使用方法 |
AU2020264485A1 (en) | 2019-04-30 | 2021-12-02 | Abbvie Inc. | Substituted cycloalkyls as modulators of the integrated stress pathway |
FR3095592B1 (fr) * | 2019-05-02 | 2021-05-21 | Unither Pharmaceuticals | Composition à base de gomme gellane et de phényléphrine, procédé de fabrication et utilisation comme produit ophtalmique |
US10973780B2 (en) | 2019-05-15 | 2021-04-13 | Bexson Biomedical, Inc. | Ketamine formulation for subcutaneous injection |
BR112022004475A2 (pt) | 2019-09-18 | 2022-05-31 | Novartis Ag | Proteínas de fusão nkg2d e usos das mesmas |
JP2022548696A (ja) | 2019-09-18 | 2022-11-21 | 武田薬品工業株式会社 | 血漿カリクレインインヒビター及びその使用 |
WO2021055589A1 (en) | 2019-09-18 | 2021-03-25 | Shire Human Genetic Therapies, Inc. | Heteroaryl plasma kallikrein inhibitors |
WO2021097339A1 (en) | 2019-11-13 | 2021-05-20 | Rapt Therapeutics, Inc. | Crystalline forms of c-c chemokine receptor type 4 antagonist and uses thereof |
AU2020407648A1 (en) | 2019-12-18 | 2022-06-30 | Abbvie Inc. | Protein tyrosine phosphatase inhibitors and methods of use thereof |
EP4126076A1 (en) | 2020-03-31 | 2023-02-08 | Sentiss Pharma Private Limited | A sterilization process of timolol gel forming solution through aseptic filtration |
GR1010024B (el) | 2020-05-06 | 2021-06-01 | Φαρματεν Α.Β.Ε.Ε. | Φαρμακευτικο σκευασμα ελευθερο συντηρητικου για οφθαλμικη χορηγηση που περιλαμβανει βριμονιδινη |
EP4153564A1 (en) | 2020-05-19 | 2023-03-29 | Cybin IRL Limited | Deuterated tryptamine derivatives and methods of use |
KR20230053611A (ko) | 2020-08-18 | 2023-04-21 | 사이빈 아이알엘 리미티드 | 펜에틸아민 유도체, 조성물, 및 사용 방법 |
PE20231656A1 (es) | 2020-11-02 | 2023-10-17 | Trethera Corp | Formas cristalinas de un inhibidor de cinasa de desoxicitidina y sus usos |
CA3198795A1 (en) | 2020-11-18 | 2022-05-27 | Jeffrey Becker | Complexing agent salt formulations of pharmaceutical compounds |
WO2022133237A2 (en) | 2020-12-18 | 2022-06-23 | Cornell University | Methods of treating neurodegenerative disorders and stat3-linked cancers using suppressors of electron leak |
WO2022197641A1 (en) | 2021-03-15 | 2022-09-22 | Rapt Therapeutics, Inc. | 1h-pyrazolo[3,4-d]pyrimidin-6-yl-amine derivatives as hematopoietic progenitor kinase 1 (hpk1) modulators and/or inhibitors for the treatment of cancer and other diseases |
KR20240004296A (ko) | 2021-03-17 | 2024-01-11 | 다께다 파머수티컬 컴패니 리미티드 | 혈장 칼리크레인의 헤테로아릴 억제제 |
JP2024510502A (ja) | 2021-03-17 | 2024-03-07 | 武田薬品工業株式会社 | 血漿カリクレインのイミダゾピリジニル阻害剤 |
WO2022197756A1 (en) | 2021-03-17 | 2022-09-22 | Shire Human Genetic Therapies, Inc. | Plasma kallikrein inhibitors |
EP4308229A1 (en) | 2021-03-17 | 2024-01-24 | Takeda Pharmaceutical Company Limited | Inhibitors of plasma kallikrein |
WO2022197789A1 (en) | 2021-03-17 | 2022-09-22 | Shire Human Genetic Therapies, Inc. | Polycyclic inhibitors of plasma kallikrein |
WO2023156453A1 (en) | 2022-02-15 | 2023-08-24 | Cybin Irl Limited | Phenethylamine derivatives, compositions, and methods of use |
WO2023156450A1 (en) | 2022-02-15 | 2023-08-24 | Cybin Irl Limited | Therapeutic phenethylamine compositions and methods of use |
US20230322741A1 (en) | 2022-04-06 | 2023-10-12 | Rapt Therapeutics, Inc. | Chemokine receptor modulators and uses thereof |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2441729A (en) * | 1943-12-08 | 1948-05-18 | Kelco Co | Algin gel-forming compositions |
US2935447A (en) * | 1957-02-19 | 1960-05-03 | Kelco Co | Appetite depressant containing alginate |
FR1312244A (fr) * | 1962-01-09 | 1962-12-14 | Bernburg Serum Werk Veb | Procédé de fabrication de supports de pommade exempts de corps gras |
BE731578A (zh) * | 1969-04-16 | 1969-10-01 | ||
US4013792A (en) * | 1974-04-11 | 1977-03-22 | Warner-Lambert Company | Process for the production of base for topical steroids |
AU7776275A (en) * | 1974-04-11 | 1976-08-05 | Warner Lambert Co | Production of base for topical steroids |
NL188266C (nl) * | 1975-07-29 | 1992-05-18 | Merck & Co Inc | Werkwijze ter bereiding van een oogheelkundig inplantaat. |
US4039662A (en) * | 1975-12-04 | 1977-08-02 | Alcon Laboratories, Inc. | Ophthalmic solution |
US4188373A (en) * | 1976-02-26 | 1980-02-12 | Cooper Laboratories, Inc. | Clear, water-miscible, liquid pharmaceutical vehicles and compositions which gel at body temperature for drug delivery to mucous membranes |
CA1072413A (en) * | 1976-07-13 | 1980-02-26 | West Laboratories | Poloxamer gel systems with gelling temperatures higher than room temperature |
US4136177A (en) * | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Xanthan gum therapeutic compositions |
US4136173A (en) * | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Mixed xanthan gum and locust beam gum therapeutic compositions |
US4326053A (en) * | 1978-12-04 | 1982-04-20 | Merck & Co., Inc. | Polysaccharide S-60 and bacterial fermentation process for its preparation |
KR830002802B1 (ko) * | 1978-12-04 | 1983-12-16 | 제임스 에프 · 너우톤 | 박테리아 발효에 의한 다당류 s-60의 제조방법 |
US4409205A (en) * | 1979-03-05 | 1983-10-11 | Cooper Laboratories, Inc. | Ophthalmic solution |
US4407792A (en) * | 1979-05-09 | 1983-10-04 | Alcon Laboratories, Inc. | Sustained release ophthalmic drug dosage |
US4474751A (en) * | 1983-05-16 | 1984-10-02 | Merck & Co., Inc. | Ophthalmic drug delivery system utilizing thermosetting gels |
US4563366A (en) * | 1983-05-31 | 1986-01-07 | Merck & Co., Inc. | Non-heated gellan gum gels |
US4503084A (en) * | 1983-05-31 | 1985-03-05 | Merck & Co., Inc. | Non-heated gellan gum gels |
GB8318403D0 (en) * | 1983-07-07 | 1983-08-10 | Sutherland I W | Gel-forming polysaccharides |
DE3335593A1 (de) * | 1983-09-30 | 1985-04-11 | Diamalt AG, 8000 München | Gelier- und verdickungsmittel auf der basis von cassia-galactomannanen |
US4717713A (en) * | 1983-10-31 | 1988-01-05 | Research Corporation | Controlled release liquid pharmaceutical |
US4551456A (en) * | 1983-11-14 | 1985-11-05 | Merck & Co., Inc. | Ophthalmic use of norfloxacin and related antibiotics |
US4517216A (en) * | 1984-03-05 | 1985-05-14 | Merck & Co., Inc. | Gellan gum/gelatin blends |
GB8431699D0 (en) * | 1984-12-14 | 1985-01-30 | Mars G B Ltd | Gel system |
-
1985
- 1985-10-03 FR FR8514689A patent/FR2588189B1/fr not_active Expired
-
1986
- 1986-09-17 IE IE248186A patent/IE59464B1/en not_active IP Right Cessation
- 1986-09-23 NZ NZ217662A patent/NZ217662A/xx unknown
- 1986-09-25 IL IL80156A patent/IL80156A/xx not_active IP Right Cessation
- 1986-09-25 US US06/911,606 patent/US4861760A/en not_active Expired - Lifetime
- 1986-09-25 GR GR862444A patent/GR862444B/el unknown
- 1986-09-26 AU AU63189/86A patent/AU595240B2/en not_active Expired
- 1986-09-30 ZA ZA867464A patent/ZA867464B/xx unknown
- 1986-09-30 CN CN86106637A patent/CN1046094C/zh not_active Expired - Lifetime
- 1986-10-01 PT PT83471A patent/PT83471B/pt unknown
- 1986-10-02 JP JP61233369A patent/JPH0667853B2/ja not_active Expired - Lifetime
- 1986-10-02 AT AT86402170T patent/ATE72990T1/de not_active IP Right Cessation
- 1986-10-02 NO NO863916A patent/NO173212C/no unknown
- 1986-10-02 FI FI863990A patent/FI91217C/fi not_active IP Right Cessation
- 1986-10-02 DK DK469886A patent/DK170500B1/da not_active IP Right Cessation
- 1986-10-02 EP EP86402170A patent/EP0227494B1/en not_active Expired - Lifetime
- 1986-10-02 LU LU88694C patent/LU88694I2/fr unknown
- 1986-10-02 ES ES8602366A patent/ES2002401A6/es not_active Expired
- 1986-10-02 DE DE198686402170T patent/DE227494T1/de active Pending
- 1986-10-02 DE DE8686402170T patent/DE3684121D1/de not_active Expired - Lifetime
- 1986-10-02 KR KR1019860008277A patent/KR940000229B1/ko not_active IP Right Cessation
- 1986-10-03 CA CA000519753A patent/CA1280367C/en not_active Expired - Lifetime
-
1994
- 1994-05-05 HK HK42594A patent/HK42594A/xx not_active IP Right Cessation
-
1995
- 1995-04-10 NO NO1995003C patent/NO1995003I1/no unknown
- 1995-08-07 NL NL950012C patent/NL950012I1/nl unknown
- 1995-08-29 LV LV950262A patent/LV5725B4/xx unknown
- 1995-10-20 CY CY177995A patent/CY1779A/xx unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1046094C (zh) | 多糖体用于制备原位胶凝的眼科组合物的用途 | |
CN1229110C (zh) | 含半乳甘露聚糖聚合物和硼酸盐的眼用组合物 | |
JP4880657B2 (ja) | 粘膜表面への改良された薬物供給 | |
US8389014B2 (en) | Gel useful for the delivery of ophthalmic drugs | |
US5516808A (en) | Topical cellulose pharmaceutical formulation | |
CN107847432A (zh) | D2o稳定化的药物制剂 | |
TW200826963A (en) | Water insoluble polymer matrix for drug delivery | |
JP2014028822A (ja) | サーチュイン活性化剤を用いる眼処置 | |
JP2008520547A (ja) | 眼部送達のためのポリマー送達処方 | |
JPH06116137A (ja) | 局所的眼薬組成物 | |
MX2010012933A (es) | Composiciones farmaceuticas que contienen una droga antibiotica de fluoroquinolona. | |
CN1509172A (zh) | 哌仑西平眼用凝胶剂 | |
CN101810563B (zh) | 他克莫司眼用在体凝胶制剂及其制备方法 | |
CN102066402B (zh) | 肽衍生物以及含有肽衍生物的用于促进泪液分泌的组合物 | |
CN101077352A (zh) | 含乳糖酸阿奇霉素的眼用制剂 | |
JP3974431B2 (ja) | アルギン酸含有組成物 | |
JPH04210910A (ja) | 少なくとも1種の有効成分を含む脂質微粒子に基づく眼科用液体組成物 | |
CN101278908A (zh) | 一种可以显著增加药物效果的滴眼液 | |
JPH0565221A (ja) | 眼科用微小球 | |
CN87107231A (zh) | 治疗白内障的药物配方 | |
JP2006348055A (ja) | アルギン酸含有組成物 | |
CN104523575B (zh) | 一种盐酸羟苄唑眼用凝胶剂及其制备方法 | |
CN115212200B (zh) | 用于治疗糖尿病并发症的含葛根素的复方制剂及其制备方法 | |
JP2011008072A (ja) | コンタクトレンズの洗浄方法及びこれに用いる洗浄助剤 | |
CN1281211C (zh) | 噁唑烷酮类物质在制备治疗哺乳动物眼部感染的药物中的用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C53 | Correction of patent of invention or patent application | ||
CB02 | Change of applicant information |
Applicant after: Mokshapo and Dumchbre Experimental Center SNC Applicant before: Mokshapo and Dumchbre Experimental Center |
|
COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: LABORATOIRES MERCK SHARP + DOHME CHIBRET (FR) 3, AVENUE HOCHE, 75008, PARIS, FR TO: LABORATOIRES MERCK SHARP + DOHME CHIBRET (FR) 3, AVENUE HOCHE, 75008, PARIS, FRSNC |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C17 | Cessation of patent right | ||
CX01 | Expiry of patent term |