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1. 发明授权

US10507182B2 Remote loading of sparingly water-soluble drugs into liposomes 有权
公开(公告)号：US10507182B2
公开(公告)日：2019-12-17
申请号：US16126799
申请日：2018-09-10
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. Hayes , Charles O. Noble , Francis C. Szoka, Jr.
IPC分类号： A61K9/127 , A61K31/4196 , A61K31/496 , A61K38/07 , A61K9/00 , A61K31/5377 , B01J13/08 , A61K9/19
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (

2. 发明申请

US20140220111A1 REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPOSOMES 审中-公开
公开(公告)号：US20140220111A1
公开(公告)日：2014-08-07
申请号：US14171654
申请日：2014-02-03
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA, JR.
IPC分类号： A61K9/127 , A61K38/07
CPC分类号： A61K9/1278 , A61K9/0019 , A61K9/1271 , A61K9/1275 , A61K9/19 , A61K31/4196 , A61K31/496 , A61K31/5377 , A61K38/07 , B01J13/08
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (

3. 发明申请

US20140220110A1 REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPOSOMES 审中-公开
标题翻译：将可溶性水溶性药物远程装载到脂质体中
公开(公告)号：US20140220110A1
公开(公告)日：2014-08-07
申请号：US14171619
申请日：2014-02-03
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA, JR.
IPC分类号： A61K9/127 , A61K31/496 , A61K31/4196 , A61K38/07
CPC分类号： A61K9/1278 , A61K9/0019 , A61K9/1271 , A61K9/1275 , A61K9/19 , A61K31/4196 , A61K31/496 , A61K31/5377 , A61K38/07 , B01J13/08
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (
摘要翻译：本发明提供含有用于治疗危及生命的疾病的微溶药物的脂质体组合物。将药物包封在脂质体内的优选方法是通过远程或主动负载。将药物远程加载到含有跨膜电化学梯度的脂质体中通过将脂质体悬浮液与药物溶液共混来引发，由此化合物的中性形式自由进入脂质体并变得静电，从而防止反向转移出脂质体。在脂质体内部存在化合物的连续堆积，直到消耗电化学梯度或将所有药物包封在脂质体中。然而，如文献中所述的这种方法已经被限制在可溶于水溶液或溶解成水溶性络合物的药物中。本发明描述了用于远程装载具有低水溶性（<2mg / mL）的药物的组合物和方法。在优选的实施方案中，增溶剂中的药物与脂质体在水悬浮液中混合，使得增溶剂的浓度降低到其使药物完全溶解的能力以下。这导致药物沉淀，但保持远程加载能力。该方法是可扩展的，并且在其中优化脂质组合物和远程加载剂的脂质体中，所得药物负载的脂质体的特征在于当将脂质体包封的药物施用于学科。

4. 发明授权

US10722467B2 Remote loading of sparingly water-soluble drugs into liposomes 有权
公开(公告)号：US10722467B2
公开(公告)日：2020-07-28
申请号：US16454555
申请日：2019-06-27
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. Hayes , Charles O. Noble , Francis C. Szoka, Jr.
IPC分类号： A61K9/127 , A61K31/4196 , A61K31/496 , A61K38/07 , A61K31/5377 , A61K9/00 , B01J13/08 , A61K9/19
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (

5. 发明申请

US20170231910A1 PHARMACEUTICAL FORMULATIONS OF CHELATING AGENTS AS A METAL REMOVAL TREATMENT SYSTEM 审中-公开
公开(公告)号：US20170231910A1
公开(公告)日：2017-08-17
申请号：US15503001
申请日：2015-08-12
申请人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA, JR. , ZONEONE PHARMA, INC.
发明人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA, JR.
IPC分类号： A61K9/127 , B01J13/08 , B01J13/20 , A61K31/16 , A61K31/4196
CPC分类号： A61K9/127 , A61K9/1272 , A61K31/16 , A61K31/195 , A61K31/4196 , A61K31/663 , A61K31/704 , B01J13/08 , B01J13/203
摘要： The present invention provides liposomes loaded with chelating agents, pharmaceutical formulations including these liposomes and methods of making chelating agent liposomes. Because the chelating agents are loaded in the liposome with high efficiencies, the liposomes are of use in treatment of metal ion overload in subjects. The liposomes can also contain essential trace metals to compensate for the off target effect of removal of endogenous non-target trace metals by administration of the chelator. The liposomes can include two or more different chelating agents of different structures and affinities for metal ions.

6. 发明申请

US20170128366A1 PHARMACEUTICAL FORMULATIONS OF CHELATING AGENTS AS A METAL REMOVAL TREATMENT SYSTEM 审中-公开
公开(公告)号：US20170128366A1
公开(公告)日：2017-05-11
申请号：US15413362
申请日：2017-01-23
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA, JR.
IPC分类号： A61K9/127 , A61K31/4196 , A61K31/16
CPC分类号： A61K9/127 , A61K9/19 , A61K31/16 , A61K31/198 , A61K31/4196 , A61K31/663
摘要： The present invention provides liposomes loaded with chelating agents, pharmaceutical formulations including these liposomes and methods of making chelating agent liposomes. Because the chelating agents are loaded in the liposome with high efficiencies, the liposomes are of use in treatment of metal ion overload in subjects. The liposomes can include two or more different chelating agents of different structures and affinities for metal ions.

7. 发明申请

US20190314282A1 REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPOSOMES 审中-公开
公开(公告)号：US20190314282A1
公开(公告)日：2019-10-17
申请号：US16454555
申请日：2019-06-27
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA, JR.
IPC分类号： A61K9/127 , B01J13/08 , A61K31/5377 , A61K31/4196 , A61K9/00 , A61K38/07 , A61K31/496
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (

8. 发明申请

US20190110991A1 REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPOSOMES 审中-公开
公开(公告)号：US20190110991A1
公开(公告)日：2019-04-18
申请号：US16126799
申请日：2018-09-10
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA, JR.
IPC分类号： A61K9/127 , A61K31/4196 , A61K31/496 , A61K38/07 , A61K9/00 , A61K31/5377 , B01J13/08 , A61K9/19
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (

9. 发明授权

US10004759B2 Remote loading of sparingly water-soluble drugs into lipid vesicles 有权
公开(公告)号：US10004759B2
公开(公告)日：2018-06-26
申请号：US15502092
申请日：2015-08-04
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. Hayes , Charles O. Noble , Francis C. Szoka, Jr.
IPC分类号： A61K9/127 , A61K31/7048 , A61K9/19 , A61K38/07 , A61K31/496 , A61K31/4196 , A61K31/337 , A61K47/02
CPC分类号： A61K31/7048 , A61K9/127 , A61K9/1271 , A61K9/1277 , A61K9/19 , A61K31/337 , A61K31/395 , A61K31/4196 , A61K31/496 , A61K31/704 , A61K38/07 , A61K47/02
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (

10. 发明申请

US20210008091A1 REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPID VESICLES 有权
公开(公告)号：US20210008091A1
公开(公告)日：2021-01-14
申请号：US16726624
申请日：2019-12-24
申请人： ZONEONE PHARMA, INC.
发明人： Mark E. HAYES , Charles O. NOBLE , Francis C. SZOKA
IPC分类号： A61K31/7048 , A61K9/127 , A61K31/395 , A61K31/704 , A61K9/19 , A61K31/337 , A61K31/4196 , A61K31/496 , A61K38/07 , A61K47/02
摘要： The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (

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