公开(公告)号：US20150366833A1

公开(公告)日：2015-12-24

申请号：US14652087

申请日：2013-12-11

Applicant: LEO LABORATORIES LIMITED

Inventor： Per-Ola Arvidsson ,  Edit Farkas ,  Chinar S. Saeed ,  Mikkel Krogh-Madsen ,  Karsten Petersson

IPC: A61K31/22 ,  A61K9/00 ,  A61K47/24 ,  A61K47/06

CPC classification number: A61K31/22 ,  A61K8/042 ,  A61K8/044 ,  A61K8/375 ,  A61K9/0014 ,  A61K9/06 ,  A61K47/06 ,  A61K47/24 ,  A61K2800/31 ,  A61Q19/00

Abstract: Substantially anhydrous topical gel compositions comprising ingenol-3-angelate as a suspension in non-aqueous carriers.

Abstract translation: 基本上无水的局部凝胶组合物，其包含在非水载体中作为悬浮液的内酯-3-当归。

公开(公告)号：US20150133543A1

公开(公告)日：2015-05-14

申请号：US14406509

申请日：2013-06-07

Applicant: LEO Laboratories Limited

Inventor： Per-Ola Arvidsson ,  Edit Farkas ,  Karsten Petersson ,  Chinar S. Saeed

IPC: A61K47/44 ,  A61K31/22 ,  A61K47/06 ,  A61K47/14 ,  A61K47/12 ,  A61K9/00 ,  A61K47/10

CPC classification number: A61K47/44 ,  A61K9/0014 ,  A61K31/22 ,  A61K47/06 ,  A61K47/10 ,  A61K47/12 ,  A61K47/14

Abstract: A substantially anhydrous pharmaceutical gel composition for cutaneous application comprising an ingenol derivative in dissolved or solubilized form, a solvent mixture of (a) a hydrophilic non-ionic surfactant; (b) a lipophilic non-ionic co-surfactant; (c) an oil; the composition further comprising an acidic compound, a co-solvent, a viscosity-increasing agent and a pharmaceutically acceptable, substantially anhydrous, non-solvent lipid carrier.

Abstract translation: 一种用于皮肤应用的基本上无水的药物凝胶组合物，其包含溶解或溶解形式的烯内酯衍生物，（a）亲水性非离子表面活性剂的溶剂混合物; （b）亲脂性非离子助表面活性剂; （c）油; 所述组合物还包含酸性化合物，助溶剂，增粘剂和药学上可接受的，基本上无水的非溶剂脂质载体。

公开(公告)号：US20150025265A1

公开(公告)日：2015-01-22

申请号：US14182274

申请日：2014-02-17

Applicant: LEO LABORATORIES LIMITED

Inventor： Steven Martin Ogbourne

IPC: C07C67/52

CPC classification number: C07C67/52 ,  A61K9/0014 ,  A61K9/0034 ,  A61K9/06 ,  C07B2200/13 ,  C07C69/533 ,  C07C2603/86 ,  Y02A50/463

Abstract: The present invention relates to a novel crystalline form of ingenol mebutate, methods of preparation thereof, and to its use. More specifically, the invention relates to the conversion of amorphous ingenol mebutate (ingenol-3-angelate, PEP005) to a crystalline form, which was characterized by single crystal X-Ray crystallography (XRC), attenuated total reflectance Fourier transform infrared (FTIR-ATR) spectroscopy and Differential Scanning calorimetry (DSC).

Abstract translation: 本发明涉及新戊烯酮甲酸酯的结晶形式，其制备方法及其用途。 更具体地说，本发明涉及以单结晶X射线晶体学（XRC），衰减全反射傅立叶变换红外（FTIR-3）为特征的无定形内酯酚酸酯（茚满醇-3-当归，PEP005）转化为结晶形式， ATR）光谱和差示扫描量热法（DSC）。

公开(公告)号：US20150024443A1

公开(公告)日：2015-01-22

申请号：US14341720

申请日：2014-07-25

Applicant: LEO Laboratories Limited

Inventor： Xifu Liang ,  Thomas Hogberg ,  Gunnar Grue-Sorensen ,  Thomas S. Moody ,  Andrew S. Rowan

IPC: C12P7/62

CPC classification number: C12P7/62 ,  C12P15/00 ,  C12Y301/01003 ,  Y02P20/52

Abstract: The invention relates to methods for preparing ingenol-3-angelate from ingenol or ingenol derivatives.

Abstract translation: 本发明涉及由烯内酯或异山梨醇衍生物制备西叶醇-3-当归的方法。

公开(公告)号：US20140357712A1

公开(公告)日：2014-12-04

申请号：US14269055

申请日：2014-05-02

Applicant: LEO Laboratories Limited

Inventor： Marc Barry Brown ,  Michael Crothers ,  Tahir Nazir

IPC: A61K31/215

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K9/06 ,  A61K31/215 ,  A61K36/47 ,  A61K47/10 ,  A61K47/12 ,  A61K47/32 ,  A61K47/38

Abstract: Ingenol angelate is a potent anticancer agent, and can be stabilised by dissolving it in an aprotic solvent in the presence of an acidic buffer.

Abstract translation: 当归酸根是一种有效的抗癌剂，可以通过在酸性缓冲液存在下将其溶于非质子溶剂而稳定化。

公开(公告)号：US20140242012A1

公开(公告)日：2014-08-28

申请号：US14139869

申请日：2013-12-23

Applicant: LEO Laboratories Limited

Inventor： Sarah-Jane Cozzi ,  Andreas Suhrbier ,  Steven Martin Ogbourne

IPC: A61K31/22 ,  A61Q19/02 ,  A61K9/00 ,  A61K8/37

CPC classification number: A61K31/22 ,  A61K8/375 ,  A61K9/0014 ,  A61Q19/004 ,  A61Q19/02

Abstract: The present invention is directed to the prophylatic field treatment of photodamaged skin with topical ingenol mebutate. More specifically, the present invention concerns field-directed treatment of UV-damaged skin with topical ingenol mebutate for reducing the number of skin lesions that emerge from the UV-damaged skin over time. In addition, the present invention concerns field-directed treatment for removing photodamaged skin, mutated keratinocytes, cutaneous immunosuppressive environments and/or p53+ patches caused by UV with topical ingenol mebutate. By way of example, the present invention is directed to treating photodamaged skin with topical ingenol mebutate at about 0.05% concentration.The present invention is also concerned with the treatment of SCC tumors with topical ingenol mebutate for reducing the number of SCC tumors. By example, the present invention is directed to treating and curing SCC xenografts with topical ingenol mebutate at about 0.25% concentration.The present invention is further directed to a topical field-directed treatment for the removal of tattoos from skin with ingenol mebutate. By way of example, the present invention is directed to removing tattoos with topical ingenol mebutate at concentrations of up to about 0.25%.

Abstract translation: 本发明涉及用局部西梅替丁配方对光损伤皮肤进行预防性治疗。 更具体地说，本发明涉及用局部用异麦芽酮甲酸酯配制的UV损伤皮肤的现场定向治疗，以减少随时间推移从UV损伤的皮肤中出现的皮肤病变的数量。 此外，本发明涉及用于去除光损伤的皮肤，突变的角质形成细胞，皮肤免疫抑制环境和/或由局部西梅洛尔配方产生的UV引起的p53 +斑块的场定向治疗。 作为实例，本发明涉及以约0.05％浓度处理外用西来诺梅酸甲酯处理光损伤皮肤。 本发明还涉及用局部西梅替丁治疗SCC肿瘤以减少SCC肿瘤的数量。 例如，本发明涉及以约0.25％浓度处理和固化SCC异种移植物，其中外用西ing酚甲酸酯。 本发明进一步涉及用内酯醇甲酸酯从皮肤去除纹身的局部场地定向治疗。 举例来说，本发明旨在以高达约0.25％的浓度去除外用西en酚甲酸酯的纹身。

公开(公告)号：US08536163B2

公开(公告)日：2013-09-17

申请号：US13769821

申请日：2013-02-18

Applicant: Leo Laboratories Limited

Inventor： Marc Barry Brown ,  Michael Crothers ,  Tahir Nazir

IPC: A61K31/25 ,  A61P35/00

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K9/06 ,  A61K31/215 ,  A61K36/47 ,  A61K47/10 ,  A61K47/12 ,  A61K47/32 ,  A61K47/38

Abstract: Ingenol angelate is a potent anticancer agent, and can be stabilized by dissolving it in an aprotic solvent in the presence of an acidic buffer.

公开(公告)号：US20180289654A1

公开(公告)日：2018-10-11

申请号：US15816712

申请日：2017-11-17

Applicant: LEO Laboratories Limited

Inventor： Marc Barry Brown ,  Michael Edward Donald Crothers ,  Tahir Nazir

IPC: A61K31/22 ,  A61K31/215 ,  A61K36/47 ,  A61K47/38 ,  A61K9/00 ,  A61K47/12 ,  A61K47/10 ,  A61K9/06 ,  A61K47/32

Abstract: Ingenol angelate is a potent anticancer agent, and can be stabilised by dissolving it in an aprotic solvent in the presence of an acidic buffer.

公开(公告)号：US09861603B2

公开(公告)日：2018-01-09

申请号：US15163454

申请日：2016-05-24

Applicant: LEO Laboratories Limited

Inventor： Marc Barry Brown ,  Michael Edward Donald Crothers ,  Tahir Nazir

IPC: A61K31/25 ,  A61P35/00 ,  A61K31/22 ,  A61K9/00 ,  A61K9/06 ,  A61K47/10 ,  A61K47/12 ,  A61K47/32 ,  A61K31/215 ,  A61K47/38 ,  A61K36/47

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K9/06 ,  A61K31/215 ,  A61K36/47 ,  A61K47/10 ,  A61K47/12 ,  A61K47/32 ,  A61K47/38

Abstract: Ingenol angelate is a potent anticancer agent, and can be stabilized by dissolving it in an aprotic solvent in the presence of an acidic buffer.

公开(公告)号：US09820959B2

公开(公告)日：2017-11-21

申请号：US15163390

申请日：2016-05-24

Applicant: LEO Laboratories Limited

Inventor： Marc Barry Brown ,  Michael Edward Donald Crothers ,  Tahir Nazir

IPC: A61K31/25 ,  A61P35/00 ,  A61K31/22 ,  A61K9/00 ,  A61K9/06 ,  A61K47/10 ,  A61K47/12 ,  A61K47/32 ,  A61K31/215 ,  A61K47/38 ,  A61K36/47

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K9/06 ,  A61K31/215 ,  A61K36/47 ,  A61K47/10 ,  A61K47/12 ,  A61K47/32 ,  A61K47/38

Abstract: Ingenol angelate is a potent anticancer agent, and can be stabilized by dissolving it in an aprotic solvent in the presence of an acidic buffer.