公开(公告)号：US20110142917A1

公开(公告)日：2011-06-16

申请号：US12994725

申请日：2009-06-07

申请人： Egvenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

发明人： Egvenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

IPC分类号： A61K31/713 ,  A61K31/7088 ,  A61K9/127 ,  A61K33/24 ,  A61P27/16

CPC分类号： A61K31/713 ,  A61K9/0046 ,  C12N15/113 ,  C12N2310/14

摘要： The present invention relates to pharmaceutical compositions useful for topical, non-invasive delivery of an oligonucleotide to the ear and to methods for the treatment of an ear disorder, including hearing loss arising from chemical-induced ototoxicity, acoustic trauma and presbycusis; and microbial infections. The method comprises topically administering to the ear of a subject in need thereof a pharmaceutical composition comprising an inhibitory oligonucleotide, a permeability enhancer and a pharmaceutically acceptable carrier, wherein the oligonucleotide reduces or inhibits expression of a gene associated with the ear disorder in the subject.

摘要翻译： 本发明涉及可用于向耳部局部非侵入性递送寡核苷酸的药物组合物和用于治疗耳朵疾病的方法，包括由化学引起的耳毒性，声学创伤和老年性耳聋引起的听力损失; 和微生物感染。 该方法包括向有需要的受试者的耳部局部施用包含抑制性寡核苷酸，通透性增强剂和药学上可接受的载体的药物组合物，其中所述寡核苷酸降低或抑制与受试者相关的耳部疾病相关基因的表达。

公开(公告)号：US20110229557A1

公开(公告)日：2011-09-22

申请号：US13062161

申请日：2009-10-22

申请人： Elena Feinstein ,  Evgenia Alpert ,  Igor Mett ,  Amir Bar-Ilan ,  Igor Spivak ,  Hagar Kalinski ,  Netanja Slager

发明人： Elena Feinstein ,  Evgenia Alpert ,  Igor Mett ,  Amir Bar-Ilan ,  Igor Spivak ,  Hagar Kalinski ,  Netanja Slager

IPC分类号： A61K31/713 ,  C07H21/02 ,  A61K9/14 ,  A61K9/127 ,  A61P27/02

CPC分类号： C12N15/113 ,  A61K9/0048 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2320/30

摘要： The present invention relates to compositions and methods for inhibiting loss of a retinal ganglion cell in a subject, comprising non-invasively applying to the surface of the eye of the subject an ophthalmic composition comprising a therapeutically effective amount of at 5 least one siRNA which down regulates expression of a target gene associated with loss of the retinal ganglion cell, thereby inhibiting loss of the retinal ganglion cell in the subject. The methods of the invention also relate to the use of chemically modified siRNA compounds possessing structural motifs which down-regulate the expression of human genes expressed in retinal tissue in the mammalian eye.

摘要翻译： 本发明涉及用于抑制受试者中视网膜神经节细胞损失的组合物和方法，包括非侵入性地施用于受试者眼睛表面的眼科组合物，其包含治疗有效量的至少一种siRNA，所述siRNA下降 调节与视网膜神经节细胞丧失相关的靶基因的表达，从而抑制受试者中视网膜神经节细胞的损失。 本发明的方法还涉及具有下调哺乳动物眼睛中视网膜组织中表达的人类基因表达的结构基序的化学修饰的siRNA化合物的用途。

公开(公告)号：US08765931B2

公开(公告)日：2014-07-01

申请号：US13062161

申请日：2009-10-22

申请人： Elena Feinstein ,  Evgenia Alpert ,  Igor Mett ,  Amir Bar-Ilan ,  Igor Spivak ,  Hagar Kalinski ,  Netanja Slager ,  James D. Thompson

发明人： Elena Feinstein ,  Evgenia Alpert ,  Igor Mett ,  Amir Bar-Ilan ,  Igor Spivak ,  Hagar Kalinski ,  Netanja Slager ,  James D. Thompson

IPC分类号： C07H21/04 ,  C12N15/11

CPC分类号： C12N15/113 ,  A61K9/0048 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2320/30

摘要： The present invention relates to compositions and methods for inhibiting loss of a retinal ganglion cell in a subject, comprising non-invasively applying to the surface of the eye of the subject an ophthalmic composition comprising a therapeutically effective amount of at 5 least one siRNA which down regulates expression of a target gene associated with loss of the retinal ganglion cell, thereby inhibiting loss of the retinal ganglion cell in the subject. The methods of the invention also relate to the use of chemically modified siRNA compounds possessing structural motifs which down-regulate the expression of human genes expressed in retinal tissue in the mammalian eye.

摘要翻译： 本发明涉及用于抑制受试者中视网膜神经节细胞损失的组合物和方法，包括非侵入性地施用于受试者眼睛表面的眼用组合物，其包含治疗有效量的至少一种siRNA，所述siRNA下降 调节与视网膜神经节细胞丧失相关的靶基因的表达，从而抑制受试者中视网膜神经节细胞的损失。 本发明的方法还涉及具有下调哺乳动物眼睛中视网膜组织中表达的人类基因表达的结构基序的化学修饰的siRNA化合物的用途。

公开(公告)号：US08431692B2

公开(公告)日：2013-04-30

申请号：US12994725

申请日：2009-06-07

申请人： Egvenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

发明人： Egvenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

IPC分类号： C07H21/04 ,  C07H21/02 ,  A61K48/00

CPC分类号： A61K31/713 ,  A61K9/0046 ,  C12N15/113 ,  C12N2310/14

摘要： The present invention relates to pharmaceutical compositions useful for topical, non-invasive delivery of an oligonucleotide to the ear and to methods for the treatment of an ear disorder, including hearing loss arising from chemical-induced ototoxicity, acoustic trauma and presbycusis; and microbial infections. The method comprises topically administering to the ear of a subject in need thereof a pharmaceutical composition comprising an inhibitory oligonucleotide, a permeability enhancer and a pharmaceutically acceptable carrier, wherein the oligonucleotide reduces or inhibits expression of a gene associated with the ear disorder in the subject.

公开(公告)号：US5496811A

公开(公告)日：1996-03-05

申请号：US854

申请日：1993-01-05

申请人： Haim Aviv ,  Doron Friedman ,  Amir Bar-Ilan ,  Micha Vered

发明人： Haim Aviv ,  Doron Friedman ,  Amir Bar-Ilan ,  Micha Vered

IPC分类号： A61K9/00 ,  A61K9/107 ,  A61K31/685 ,  A61K31/22 ,  A61K31/225 ,  A61K31/66

CPC分类号： A61K9/0048 ,  A61K9/1075 ,  Y10S514/912

摘要： An ocular drug delivery vehicle of an oil-in-water submicron emulsion comprising about 0.5 to 50% of a first component of an oil, about 0.1 to 10% of a second component of an emulsifier, about 0.05 to 5% of a non-ionic surfactant and an aqueous component, with the mean droplet size being in the submicron range, i.e., below about 0.5 .mu.m and preferably between about 0.1 and 0.3 .mu.m. Also, topical pharmaceutical compositions containing a drug such as an anti-glaucoma drug, beta adrenergic blocker or other autonomic system drug, a local anesthetic, a steroid, a non-steroidal anti-inflammatory drug, an antibiotic drug, an antifungal drug, an antiviral drug or combinations thereof and the vehicle described above. Methods of administering such vehicles or compositions to the eye of a patient while reducing irritation thereof and providing increased bioavailability of the drug.

摘要翻译： 一种水包油亚微米乳剂的眼药物递送载体，其包含约0.5至50％的第一组分油，约0.1至10重量％的第二组分的乳化剂，约0.05至5重量％ 离子表面活性剂和水性组分，平均液滴尺寸在亚微米范围内，即低于约0.5μm，优选在约0.1和0.3μm之间。 此外，含有药物如抗青光眼药物，β-肾上腺素能阻滞剂或其他自主神经系统药物的局部药物组合物，局部麻醉剂，类固醇，非甾体抗炎药，抗生素药物，抗真菌药物 抗病毒药物或其组合和上述载体。 将这些载体或组合物施用于患者的眼睛同时减少其刺激并提供药物的增加的生物利用度的方法。

公开(公告)号：US09089591B2

公开(公告)日：2015-07-28

申请号：US13867837

申请日：2013-04-22

申请人： Evgenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

发明人： Evgenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  A61K31/713 ,  A61K9/00 ,  C12N15/113

CPC分类号： A61K31/713 ,  A61K9/0046 ,  C12N15/113 ,  C12N2310/14

摘要： The present invention relates to pharmaceutical compositions useful for topical, non-invasive delivery of an oligonucleotide to the ear and to methods for the treatment of an ear disorder, including hearing loss arising from chemical-induced ototoxicity, acoustic trauma and presbycusis; and microbial infections. The method comprises topically administering to the ear of a subject in need thereof a pharmaceutical composition comprising an inhibitory oligonucleotide, a permeability enhancer and a pharmaceutically acceptable carrier, wherein the oligonucleotide reduces or inhibits expression of a gene associated with the ear disorder in the subject.

摘要翻译： 本发明涉及可用于向耳部局部非侵入性递送寡核苷酸的药物组合物和用于治疗耳朵疾病的方法，包括由化学引起的耳毒性，声学创伤和老年性耳聋引起的听力损失; 和微生物感染。 该方法包括向有需要的受试者的耳部局部施用包含抑制性寡核苷酸，通透性增强剂和药学上可接受的载体的药物组合物，其中所述寡核苷酸降低或抑制与受试者相关的耳部疾病相关基因的表达。

公开(公告)号：US20140066493A1

公开(公告)日：2014-03-06

申请号：US13867837

申请日：2013-04-22

申请人： Evgenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

发明人： Evgenia Alpert ,  Igor Spivak ,  Amir Bar-Ilan

IPC分类号： A61K31/713

CPC分类号： A61K31/713 ,  A61K9/0046 ,  C12N15/113 ,  C12N2310/14

摘要： The present invention relates to pharmaceutical compositions useful for topical, non-invasive delivery of an oligonucleotide to the ear and to methods for the treatment of an ear disorder, including hearing loss arising from chemical-induced ototoxicity, acoustic trauma and presbycusis; and microbial infections. The method comprises topically administering to the ear of a subject in need thereof a pharmaceutical composition comprising an inhibitory oligonucleotide, a permeability enhancer and a pharmaceutically acceptable carrier, wherein the oligonucleotide reduces or inhibits expression of a gene associated with the ear disorder in the subject.

摘要翻译： 本发明涉及可用于向耳部局部非侵入性递送寡核苷酸的药物组合物和用于治疗耳朵疾病的方法，包括由化学引起的耳毒性，声学创伤和老年性耳聋引起的听力损失; 和微生物感染。 该方法包括向有需要的受试者的耳部局部施用包含抑制性寡核苷酸，通透性增强剂和药学上可接受的载体的药物组合物，其中所述寡核苷酸降低或抑制与受试者相关的耳部疾病相关基因的表达。