公开(公告)号：US09789078B2

公开(公告)日：2017-10-17

申请号：US14401492

申请日：2013-05-15

Applicant: LEO Laboratories Limited

Inventor： Kirsten Norrelund

IPC: A61K31/22 ,  A61K31/215 ,  A61K9/00

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K31/215

Abstract: The present invention relates to cyclic or repeated use of the ingenol mebutate for topical treatment of actinic keratosis lesions. Generally speaking, the present invention comprises a first ingenol mebutate treatment cycle and a second ingenol mebutate treatment cycle, wherein the first treatment cycle topically treats a treatment area with a topical gel formulated with ingenol mebutate at a selected dosage strength for a specified treatment regimen, and the second ingenol mebutate treatment cycle comprises topically re-treating the treatment area with the same topical ingenol mebutate gel for the same specified treatment regimen, if following the first treatment cycle, the treatment area failed to clear or failed to remain clear of AK lesions. The present invention further relates to spot or individual lesion therapy in the treatment area following the topical bi-cyclic therapy with ingenol mebutate.

公开(公告)号：US20170258769A1

公开(公告)日：2017-09-14

申请号：US15529606

申请日：2015-11-27

Applicant: LEO Laboratories Limited

Inventor： Casper Clemmensen ,  Johan Selmer ,  Kim Mark Knudsen

IPC: A61K31/42 ,  A61K9/06 ,  A61K9/00

CPC classification number: A61K31/42 ,  A61K9/0014 ,  A61K9/06 ,  A61K31/41

Abstract: The invention relates to the treatment of actinic keratosis on the trunk (except chest) and extremities with ingenol 3-(3,5-diethylisoxazole-4-carboxylate).

公开(公告)号：US09676698B2

公开(公告)日：2017-06-13

申请号：US15178112

申请日：2016-06-09

Applicant: LEO Laboratories Limited

Inventor： Thomas Hogberg ,  Gunnar Grue-Sorensen ,  Xifu Liang ,  Anne Marie Horneman ,  Anders Klarskov Petersen

IPC: C07C49/00 ,  C07C67/00 ,  C07C69/00 ,  C07D319/00 ,  C07C67/08 ,  C07C67/297 ,  C07D319/08 ,  C07C49/753 ,  C07C59/90 ,  C07F7/18 ,  C07C67/14 ,  C07D317/70 ,  C07D493/08

CPC classification number: C07C67/08 ,  C07C49/753 ,  C07C59/90 ,  C07C67/14 ,  C07C67/297 ,  C07C2603/86 ,  C07C2603/98 ,  C07D317/70 ,  C07D319/08 ,  C07D493/08 ,  C07F7/1804 ,  Y02P20/55 ,  C07C69/533

Abstract: The present invention relates to methods of producing ingenol-3-angelate (I) from ingenol (II). Furthermore, the invention relates to intermediates useful for the synthesis of ingenol-3-angelate (I) from ingenol (II) and to methods of producing said intermediates.

公开(公告)号：US09526714B2

公开(公告)日：2016-12-27

申请号：US14224063

申请日：2014-03-24

Applicant: LEO Laboratories Limited

Inventor： Torsten Skov ,  Anita Melgaard

IPC: A61K31/21 ,  A01N37/00 ,  A61K31/22 ,  A61K31/00

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K9/06 ,  A61K31/00

Abstract: The invention provides novel methods for topical treatment of skin lesions such as actinic keratosis over treatment areas up to 250 cm2.

Abstract translation: 本发明提供用于局部治疗皮肤损伤的新方法，例如高达250cm 2的治疗区域的光化性角化病。

公开(公告)号：US20160228396A1

公开(公告)日：2016-08-11

申请号：US15099291

申请日：2016-04-14

Applicant: LEO Laboratories Limited

Inventor： Lotte Groth Ladefoged ,  Per-Ola Arvidsson ,  Karsten Petersson

IPC: A61K31/22 ,  A61K9/06 ,  A61K9/00 ,  A61K47/10 ,  A61K9/70

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K9/06 ,  A61K9/7023 ,  A61K9/703 ,  A61K47/10 ,  A61K47/12 ,  A61K47/38

Abstract: The present invention relates to formulations of ingenol mebutate and methods of preparation and use thereof. More specifically, the invention relates to formulations of ingenol-3-mebutate applied to the skin with occlusion, and methods for treating or preventing diseases or conditions.

公开(公告)号：US09404131B2

公开(公告)日：2016-08-02

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 ,  C12P15/00

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：US20160089362A1

公开(公告)日：2016-03-31

申请号：US14704854

申请日：2015-05-05

Applicant: LEO Laboratories Limited

Inventor： Johan Selmer ,  Kim Mark Knudsen

IPC: A61K31/422 ,  A61K9/06 ,  A61K9/00

CPC classification number: A61K31/422 ,  A61K9/0014 ,  A61K9/06 ,  A61K31/41 ,  A61K31/4155

Abstract: The invention relates to the treatment of actinic keratosis on the trunk (except chest) or Extremities with ingenol 3-(3,5-diethylisoxazole-4-carboxylate).

Abstract translation: 本发明涉及治疗躯干（胸部除外）或四烯酚3-（3,5-二乙基异恶唑-4-羧酸酯）的四肢的光化性角化病。

公开(公告)号：US20150335606A1

公开(公告)日：2015-11-26

申请号：US14652091

申请日：2013-12-11

Applicant: LEO LABORATORIES LIMITED

Inventor： Per-Ola Arvidsson ,  Edit Farkas ,  Chinar Sami Saeed ,  Mikkel Krogh-Madsen

IPC: A61K31/22 ,  A61K9/00 ,  A61K9/06 ,  A61K9/127

CPC classification number: A61K31/22 ,  A61K9/0014 ,  A61K9/06 ,  A61K9/127 ,  A61K9/1272

Abstract: Aqueous topical liposome gel compositions comprising ingenol-3-angelate.

Abstract translation: 水性局部脂质体凝胶组合物，其包含内酯-3-天竺葵素。

公开(公告)号：US20150329463A1

公开(公告)日：2015-11-19

申请号：US14415544

申请日：2013-07-11

Applicant: LEO Laboratories Limited

Inventor： Xifu Liang

IPC: C07C67/297 ,  C07C67/08

CPC classification number: C07C67/297 ,  C07C67/00 ,  C07C67/08 ,  C07C67/29 ,  C07C2103/98 ,  C07C2603/98 ,  C07C69/533

Abstract: The present invention provides a method for preparing ingenol-3-angelate.

Abstract translation: 本发明提供了一种制备美尼芬3-angelate的方法。

公开(公告)号：US20150175622A1

公开(公告)日：2015-06-25

申请号：US14409374

申请日：2013-06-21

Applicant: LEO LABORATORIES LIMITED

Inventor： Xifu Liang ,  Thomas Högberg ,  Bjarne Nørremark ,  Kristoffer Månsson ,  Carsten Ryttersgaard ,  Gunnar Grue-Sørensen

IPC: C07D495/04 ,  A61K31/505 ,  C07D261/20 ,  A61K31/423 ,  C07D213/64 ,  A61K31/44 ,  C07D231/56 ,  A61K31/416 ,  C07D233/70 ,  A61K31/4164 ,  C07D217/24 ,  A61K31/472 ,  A61K31/4365 ,  C07D491/048 ,  A61K31/4355 ,  C07D271/07 ,  A61K31/4245 ,  C07D239/34

CPC classification number: C07D495/04 ,  A61K8/49 ,  A61K8/4926 ,  A61K8/4946 ,  A61K8/4953 ,  A61K31/416 ,  A61K31/4164 ,  A61K31/42 ,  A61K31/423 ,  A61K31/4245 ,  A61K31/4355 ,  A61K31/4365 ,  A61K31/44 ,  A61K31/47 ,  A61K31/472 ,  A61K31/505 ,  A61K31/506 ,  A61K45/06 ,  A61Q19/08 ,  C07D213/64 ,  C07D213/84 ,  C07D215/22 ,  C07D217/24 ,  C07D231/56 ,  C07D233/70 ,  C07D239/34 ,  C07D261/20 ,  C07D271/06 ,  C07D271/07 ,  C07D491/00 ,  C07D491/048 ,  C07D495/00 ,  A61K2300/00

Abstract: The present invention relates to a compound according to formula (I) wherein R1 represents optionally substituted heteroaryl, and pharmaceutically acceptable salts, hydrates, solvates or pharmaceutically acceptable and physiologically cleavable esters thereof. The invention relates further to intermediates for the preparation of said compounds, to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases, e.g. diseases associated with hyperplasia, neoplasia or dysplasia, with said compounds, to methods of treatment of cosmetic indications with said compounds, and to the use of said compounds in the manufacture of medicaments.

Abstract translation: 本发明涉及根据式（I）的化合物，其中R 1表示任选取代的杂芳基，及其药学上可接受的盐，水合物，溶剂合物或其药学上可接受的和生理上可切割的酯。 本发明进一步涉及用于制备所述化合物的中间体，用于治疗的所述化合物，包含所述化合物的药物组合物，治疗疾病的方法。 与所述化合物相关的与增生，瘤形成或发育不良相关的疾病，用所述化合物治疗化妆品适应症的方法，以及所述化合物在制备药物中的用途。