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1. 发明授权

US08110217B2 Sphingomyelin liposomes for the treatment of hyperactive bladder disorders 有权
标题翻译：鞘磷脂脂质体用于治疗膀胱过动症
公开(公告)号：US08110217B2
公开(公告)日：2012-02-07
申请号：US11546025
申请日：2006-10-11
申请人： Michael B. Chancellor , Pradeep Tyagi , Matthew O. Fraser , Yao-Chi Chuang , William C de Groat , Leaf Huang , Naoki Yoshimura
发明人： Michael B. Chancellor , Pradeep Tyagi , Matthew O. Fraser , Yao-Chi Chuang , William C de Groat , Leaf Huang , Naoki Yoshimura
IPC分类号： A61K9/127
CPC分类号： A61K9/127 , A61K9/0034 , A61K9/1272 , Y02A50/469
摘要： The present invention provides pharmaceutical compositions and methods for the instillation of lipid vehicles comprised of liposomes containing sphingomyelin or sphingomyelin metabolites to prevent, manage, ameliorate and/or treat disorders involving neuropathic pain and aberrant muscle contractions, such as what occurs in bladder hyperactivity disorders such as interstitial cystitis (IC) in animals or humans in need thereof. Also provided is a liposome-based delivery of drugs, e.g., antibiotics, pain treatments and anticancer agents, to the bladder, genitourinary tract, gastrointestinal system, pulmonary system and other organs or body systems. In particular, liposome-based delivery of vanilloid compounds, such as resiniferatoxin, capsaicin, or tinyatoxin and toxins, such as botulinum toxin is provided for the treatment of bladder conditions, including pain, inflammation, incontinence and voiding dysfunction.
摘要翻译：本发明提供用于滴注含有鞘磷脂或鞘磷脂代谢物的脂质体的脂质载体的药物组合物和方法，以预防，治疗，改善和/或治疗涉及神经性疼痛和异常肌肉收缩的疾病，例如膀胱多动障碍作为有需要的动物或人类的间质性膀胱炎（IC）。还提供了对膀胱，泌尿生殖道，胃肠系统，肺系统和其他器官或身体系统的基于脂质体的药物递送，例如抗生素，疼痛治疗和抗癌剂。特别地，提供了基于脂质体的递送香草素化合物，例如树脂毒素，辣椒素或微量毒素和毒素，例如肉毒杆菌毒素，用于治疗膀胱状况，包括疼痛，炎症，失禁和排尿功能障碍。

2. 发明授权

US06509032B1 Cationic amphiphiles 失效
标题翻译：阳离子两亲物
公开(公告)号：US06509032B1
公开(公告)日：2003-01-21
申请号：US08382893
申请日：1995-02-02
申请人： Leaf Huang , Richard M. Epand , Remo Bottega
发明人： Leaf Huang , Richard M. Epand , Remo Bottega
IPC分类号： A61K9127
CPC分类号： C07J41/0055 , A61K9/1272 , A61K47/54 , A61K47/554 , C07J9/00 , C12N15/64 , C12N15/88 , Y10T428/2984
摘要： A cationic lipid useful in transfection of cells with DNA is disclosed.
摘要翻译：公开了可用于用DNA转染细胞的阳离子脂质

3. 发明授权

US06361791B1 Stable aqueous dispersions including cationic lipids 失效
标题翻译：稳定的水分散体包括阳离子脂质
公开(公告)号：US06361791B1
公开(公告)日：2002-03-26
申请号：US08580779
申请日：1995-12-28
申请人： Leaf Huang , Richard M. Epand , Remo Bottega
发明人： Leaf Huang , Richard M. Epand , Remo Bottega
IPC分类号： A61K9127
CPC分类号： C07J41/0055 , A61K9/1272 , A61K47/54 , A61K47/554 , C07J9/00 , C12N15/64 , C12N15/88 , Y10T428/2984
摘要： A stable aqueous dispersion which comprises a cationic lipid which is a molecule which comprises a cholesterol-derived lipophilic group, a linker bond which is hydrolyzable by cellular enzymes and relatively resistant to base-catalyzed hydrolysis, a spacer arm and a cationic amino group, and an appropriate co-lipid. The invention also includes the cationic lipids and mammalian plasmid DNA or other cells in admixture with the aqueous dispersion.
摘要翻译：一种稳定的水分散体，其包含阳离子脂质，其是包含胆固醇衍生的亲脂基团的分子，可被细胞酶水解并且相对抗碱基催化水解的连接体键，间隔臂和阳离子氨基，以及合适的辅助脂质。本发明还包括与水分散体混合的阳离子脂质和哺乳动物质粒DNA或其它细胞。

4. 发明授权

US5283122A Fused liposome and acid induced method for liposome fusion 失效
标题翻译：融合脂质体和酸诱导的脂质体融合方法
公开(公告)号：US5283122A
公开(公告)日：1994-02-01
申请号：US836125
申请日：1992-02-14
申请人： Leaf Huang , Jerome Connor
发明人： Leaf Huang , Jerome Connor
IPC分类号： A61K9/127 , C12N15/88
CPC分类号： A61K9/1272 , C12N15/88 , Y10S436/829 , Y10T428/2984
摘要： Liposomes containing phosphatidylethanolamine, palmitoyl homocysteine or oleic acid or palmitic acid, fuse rapidly when the pH of the medium is reduced below 7. Liposome fusion was measured by (a) mixing of the liposomal lipids as shown by resonance energy transfer, (b) gel filtration and (c) electron microscopy. The presence of phosphatidylethanolamine or acid addition esters thereof in the liposomes greatly enhances fusion; whereas the presence of phosphatidylcholine inhibits fusion. During fusion of liposomes containing phosphatidylethanolamine:palmitoyl homocysteine (8:2), almost all of the encapsulated calcein is released. Inclusion of cholesterol (40%) in the liposomes substantially decreases leakage without impairing fusion. Those pH sensitive liposomes are fused to deliver biologically active molecules such as DNA, into living cells.
摘要翻译：含有磷脂酰乙醇胺，棕榈酰高半胱氨酸或油酸或棕榈酸的脂质体当培养基的pH值降至7以下时迅速融合。脂质体融合通过（a）如共振能量转移所示脂质体脂质的混合，（b）凝胶过滤和（c）电子显微镜。磷脂酰乙醇胺或其酸加成酯在脂质体中的存在大大增强了融合; 而磷脂酰胆碱的存在抑制融合。在含有磷脂酰乙醇胺的脂质体融合过程中，棕榈酰同型半胱氨酸（8：2）几乎全部被包裹的钙黄绿素释放出来。在脂质体中包含胆固醇（40％）可显着减少渗漏而不损害融合。将这些pH敏感的脂质体融合以将生物活性分子例如DNA递送到活细胞中。

5. 发明授权

US4789633A Fused liposome and acid induced method for liposome fusion 失效
标题翻译：融合脂质体和酸诱导的脂质体融合方法
公开(公告)号：US4789633A
公开(公告)日：1988-12-06
申请号：US602177
申请日：1984-04-19
申请人： Leaf Huang , Jerome Connor
发明人： Leaf Huang , Jerome Connor
IPC分类号： A01H1/00 , A01H5/00 , A61K9/00 , A61K9/127 , B01J13/02 , C12N5/00 , C12N5/02 , C12N5/10 , C12N15/00 , C12N15/88 , A61J5/00 , B32B5/16
CPC分类号： A61K9/127 , A61K9/1272 , C12N15/88 , Y10T428/2984
摘要： Liposomes containing phosphatidylethanolamine, palmitoyl homocysteine or oleic acid or palmitic acid, fuse rapidly when the pH of the medium is reduced below 7. Liposome fusion was measured by (a) mixing of the liposomal lipids as shown by resonance energy transfer, (b) gel filtration and (c) electron microscopy. The presence of phosphatidylethanolamine or acid addition esters thereof in the liposomes greatly enhances fusion; whereas the presence of phosphatidylcholine inhibits fusion. During fusion of liposomes containing phosphatidylethanolamine:palmitoyl homocysteine (8:2), almost all of the encapsulate calcein is released. Inclusion of cholesterol (40%) in the liposomes substantially decreases leakage without impairing fusion. Those pH sensitive liposomes are fused to deliver biologically active molecules such as DNA, into living cells.
摘要翻译：含有磷脂酰乙醇胺，棕榈酰高半胱氨酸或油酸或棕榈酸的脂质体当培养基的pH值降至7以下时迅速融合。脂质体融合通过（a）如共振能量转移所示脂质体脂质的混合，（b）凝胶过滤和（c）电子显微镜。磷脂酰乙醇胺或其酸加成酯在脂质体中的存在大大增强了融合; 而磷脂酰胆碱的存在抑制融合。在含有磷脂酰乙醇胺的脂质体融合过程中，棕榈酰同型半胱氨酸（8：2）几乎全部释放出钙黄绿素。在脂质体中包含胆固醇（40％）可显着减少渗漏而不损害融合。将这些pH敏感的脂质体融合以将生物活性分子例如DNA递送到活细胞中。

6. 发明授权

US09937128B2 Liposomes comprising a calcium phosphate-containing precipitate 有权
公开(公告)号：US09937128B2
公开(公告)日：2018-04-10
申请号：US13388538
申请日：2010-08-03
申请人： Leaf Huang , Jun Li
发明人： Leaf Huang , Jun Li
IPC分类号： A61K9/127 , A61K48/00 , C12N15/11
CPC分类号： A61K9/1271 , A61K9/1277 , A61K48/0025 , C12N15/111 , C12N2310/14 , C12N2310/3515 , C12N2320/32
摘要： Provided herein are methods and compositions for the delivery of bioactive compounds to a cell, tissue, or physiological site. The compositions comprise delivery system complexes comprising liposomes encapsulating a biodegradable ionic precipitate having incorporated therein a bioactive compound and delivery system complexes comprising a biodegradable ionic precipitate ionically bound to a surrounding lipid bilayer, wherein the biodegradable ionic precipitate comprises a bioactive compound. Also provided herein are methods for the treatment of a disease or an unwanted condition in a subject, wherein the methods comprise administering the delivery system complexes comprising bioactive compounds that have therapeutic activity against the disease or unwanted condition to the subject.

7. 发明授权

US09789129B2 Stimulation of an immune response by enantiomers of cationic lipids 有权
公开(公告)号：US09789129B2
公开(公告)日：2017-10-17
申请号：US12988236
申请日：2009-04-14
申请人： Elizabeth Ann Vasievich , Weihsu Claire Chen , Kenya Toney Johnson , Gregory Conn , Frank Bedu-Addo , Leaf Huang
发明人： Elizabeth Ann Vasievich , Weihsu Claire Chen , Kenya Toney Johnson , Gregory Conn , Frank Bedu-Addo , Leaf Huang
IPC分类号： A61K45/00 , A61K31/685
CPC分类号： A61K31/685
摘要： Compositions and methods for treating immune cells and activating immune responses are disclosed. The compositions comprise one or more optically active chiral cationic lipids.

8. 发明申请

US20120201872A1 LIPOSOMES COMPRISING A CALCIUM PHOSPHATE-CONTAINING PRECIPITATE 有权
标题翻译：包含含磷酸钙的脂肪酸
公开(公告)号：US20120201872A1
公开(公告)日：2012-08-09
申请号：US13388538
申请日：2010-08-03
申请人： Leaf Huang , Jun Li
发明人： Leaf Huang , Jun Li
IPC分类号： A61K9/127 , A61K38/02 , A61K31/713 , A61P31/00 , A61P31/04 , A61P31/10 , A61P31/12 , A61P35/00 , A61P37/02 , A61P3/00 , A61P3/08 , A61P7/02 , A61P3/06 , A61P9/00 , A61P5/14 , A61P5/16 , A61P9/12 , A61P21/02 , A61P37/08 , A61P23/02 , A61P29/00 , A61P11/14 , A61P25/20 , A61P25/18 , A61P25/22 , A61P25/24 , A61P39/06 , A61P19/08 , A61P19/02 , A61K31/7068 , B05D7/00 , A61K31/7088 , B82Y5/00
CPC分类号： A61K9/1271 , A61K9/1277 , A61K48/0025 , C12N15/111 , C12N2310/14 , C12N2310/3515 , C12N2320/32
摘要： Provided herein are methods and compositions for the delivery of bioactive compounds to a cell, tissue, or physiological site. The compositions comprise delivery system complexes comprising liposomes encapsulating a biodegradable ionic precipitate having incorporated therein a bioactive compound and delivery system complexes comprising a biodegradable ionic precipitate ionically bound to a surrounding lipid bilayer, wherein the biodegradable ionic precipitate comprises a bioactive compound. Also provided herein are methods for the treatment of a disease or an unwanted condition in a subject, wherein the methods comprise administering the delivery system complexes comprising bioactive compounds that have therapeutic activity against the disease or unwanted condition to the subject.
摘要翻译：本文提供了用于将生物活性化合物递送至细胞，组织或生理部位的方法和组合物。所述组合物包含包含脂质体的递送系统复合物，其包含其中掺入生物活性化合物的生物可降解离子沉淀物和包含与周围脂质双层离子结合的生物可降解离子沉淀物的递送系统复合物，其中所述生物可降解离子沉淀物包含生物活性化合物。本文还提供了用于治疗受试者的疾病或不需要的病症的方法，其中所述方法包括向所述受试者施用包含对疾病或不需要的病症具有治疗活性的生物活性化合物的递送系统复合物。

9. 发明申请

US20110117026A1 METHODS AND COMPOSITIONS FOR THE DELIVERY OF BIOACTIVE COMPOUNDS 审中-公开
标题翻译：用于提供生物化合物的方法和组合物
公开(公告)号：US20110117026A1
公开(公告)日：2011-05-19
申请号：US12993424
申请日：2009-05-01
申请人： Yu-Chen Tseng , Sang Kyoon Kim , Michael Hackett , Sumio Chono , Leaf Huang , Shyh-dar Li
发明人： Yu-Chen Tseng , Sang Kyoon Kim , Michael Hackett , Sumio Chono , Leaf Huang , Shyh-dar Li
IPC分类号： A61K9/127 , C12Q1/02 , C12N5/071 , A61K31/713 , A61K49/00 , A61P35/00
CPC分类号： C07C279/10 , A61K9/1271 , A61K9/1272 , A61K47/6911 , C07C279/20 , C12N15/88
摘要： The present invention provides compositions comprising delivery systems comprising a lipid vehicle, a bioactive compound, and a polyanionic carrier macromolecule that is not a carrier polynucleotide, wherein the lipid vehicle encapsulates the polynucleotide of interest and the polyanionic carrier macromolecule, and wherein the delivery system is essentially free of carrier polynucleotides. Compositions also include delivery systems comprising a lipid vehicle and a bioactive agent, wherein the lipid vehicle encapsulates the bioactive agent, and wherein the lipid vehicle comprises a covalent bilayer or a core supported bilayer comprising polycationic lipids. Other compositions provided herein comprise a delivery system comprising a polypeptide of interest and a means for delivering the polypeptide into a cell. Also provided herein are methods for making the delivery systems, methods for delivering bioactive compounds, methods for treating a disease or unwanted condition in a subject with the delivery systems, and methods for detecting apoptosis in a cell.
摘要翻译：本发明提供包含递送系统的组合物，其包含脂质载体，生物活性化合物和不是载体多核苷酸的聚阴离子载体大分子，其中所述脂质载体包封感兴趣的多核苷酸和聚阴离子载体大分子，并且其中递送系统是基本上不含载体多核苷酸。组合物还包括包含脂质载体和生物活性剂的递送系统，其中所述脂质载体包封所述生物活性剂，并且其中所述脂质载体包含共价双层或包含聚阳离子脂质的核心负载双层。本文提供的其它组合物包含包含感兴趣多肽的递送系统和用于将多肽递送至细胞的手段。本文还提供了制备递送系统的方法，用于递送生物活性化合物的方法，用于用递送系统治疗受试者的疾病或不需要的病症的方法，以及用于检测细胞凋亡的方法。

10. 发明申请

US20080153166A1 STABLE LIPID-COMPRISING DRUG DELIVERY COMPLEXES AND METHODS FOR THEIR PRODUCTION 失效
标题翻译：稳定的脂肪包裹药物递送复合物及其生产方法
公开(公告)号：US20080153166A1
公开(公告)日：2008-06-26
申请号：US11943434
申请日：2007-11-20
申请人： Leaf Huang , Xiang Gao , Frank L. Sorgi
发明人： Leaf Huang , Xiang Gao , Frank L. Sorgi
IPC分类号： C12N15/88 , C12N15/11 , C07K14/00 , C07K11/00
CPC分类号： A61K47/48315 , A61K9/1272 , A61K47/543 , A61K47/645 , C12N15/88
摘要： Novel stable, concentrated, biologically active and ready-to-use lipid-comprising drug delivery complexes and methods for their production are described. The biological activity of the complexes produced are comparable to the formulations prepared according to the prior art admixture method and upon purification, the complexes produced by the method of this invention are 50 to 500 fold more concentrated than the complexes formed by admixture. The method described herein provides for the large scale production of lipid-comprising drug delivery systems useful for gene therapy and other applications.
摘要翻译：描述了新的稳定的，浓缩的，生物活性的和即用型含脂质的药物递送复合物及其生产方法。所生成的络合物的生物活性与根据现有技术的混合方法制备的制剂相当，并且在纯化后，通过本发明的方法制备的络合物比通过混合物形成的络合物多50至500倍。本文所述的方法提供大规模生产用于基因治疗和其它应用的含脂质药物递送系统。

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