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1. 发明授权

US07287646B2 Esters of 5-aminolevulinic acid and their use as photosensitizing compounds in photochemotherapy 有权
标题翻译： 5-氨基乙酰丙酸的酯及其在光化学疗法中作为光敏化合物的用途
公开(公告)号：US07287646B2
公开(公告)日：2007-10-30
申请号：US10966408
申请日：2004-10-14
申请人： Karl E Gierskcky , Johan Moan , Qian Peng , Harald Steen , Trond Warloe , Alf Bjorseth , Jo Klaveness , Nils Nilsen , Jon Erik Braenden , Aslak Godal
发明人： Karl E Gierskcky , Johan Moan , Qian Peng , Harald Steen , Trond Warloe , Alf Bjorseth , Jo Klaveness , Nils Nilsen , Jon Erik Braenden , Aslak Godal
IPC分类号： B65D69/00 , A61K31/22 , C07C69/66
CPC分类号： C07C229/22 , A61K41/0061 , A61K49/0021 , A61K49/0052
摘要： The present invention relates to compounds being esters of 5-aminolevulinic acids or pharmaceutically acceptable salts thereof, including compounds of formula (I) R22N—CH2COCH2—CH2CO—OR1 (wherein R1 may represent alkyl optionally substituted by hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, oxo or fluoro groups and optionally interrupted by oxygen, nitrogen, sulphur or phosphorus atoms; and R2 represents a hydrogen atom or a group R1, and both R2 groups may be the identical or different), and their use in diagnosis and photochemotherapy of disorders or abnormalities of external or internal surfaces of the body, and products and kits for performing the invention.
摘要翻译：本发明涉及作为5-氨基乙酰丙酸的酯或其药学上可接受的盐的化合物，包括式（I）的化合物R 2 N 2 CH 2 其中R 1可以表示任选取代的烷基，其中R 1表示任选被取代的烷基，羟基，烷氧基，酰氧基，烷氧基羰基氧基，氨基，芳基，氧代或氟基团，且任选被氧，氮，硫或磷原子间隔; R 2表示氢原子或基团R > 1 ，并且两个R 2个基团可以相同或不同），以及它们在诊断和光化学治疗身体的外部或内部表面的障碍或异常中的用途，以及产品和用于执行本发明的试剂盒。

2. 发明申请

US20050107471A1 NEW ESTERS OF 5-AMINOLEVULINIC ACID AND THEIR USE AS PHOTOSENSITIZING COMPOUNDS IN PHOTOCHEMOTHERAPY 有权
标题翻译： 5-氨基酸的新产物及其在光电疗法中的光敏化合物的使用
公开(公告)号：US20050107471A1
公开(公告)日：2005-05-19
申请号：US10966408
申请日：2004-10-14
申请人： Karl Gierskcky , Johan Moan , Qian Peng , Harald Steen , Trond Warloe , Alf Bjorseth , Jo Klaveness , Nils Nilsen , Jon Braenden , Aslak Godal
发明人： Karl Gierskcky , Johan Moan , Qian Peng , Harald Steen , Trond Warloe , Alf Bjorseth , Jo Klaveness , Nils Nilsen , Jon Braenden , Aslak Godal
IPC分类号： A61K41/00 , A61K49/00 , C07C229/22 , A61K31/22
CPC分类号： C07C229/22 , A61K41/0061 , A61K49/0021 , A61K49/0052
摘要： The present invention relates to compounds being esters of 5-aminolevulinic acids or pharmaceutically acceptable salts thereof, including compounds of formula (I) R22N—CH2COCH2—CH2CO—OR1 (wherein R1 may represent alkyl optionally substituted by hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, oxo or fluoro groups and optionally interrupted by oxygen, nitrogen, sulphur or phosphorus atoms; and R2 represents a hydrogen atom or a group R1, and both R2 groups may be the identical or different), and their use in diagnosis and photochemotherapy of disorders or abnormalities of external or internal surfaces of the body, and products and kits for performing the invention.
摘要翻译：本发明涉及作为5-氨基乙酰丙酸的酯或其药学上可接受的盐的化合物，包括式（I）的化合物R 2 N 2 CH 2 其中R 1可以表示任选取代的烷基，其中R 1表示任选被取代的烷基，羟基，烷氧基，酰氧基，烷氧基羰基氧基，氨基，芳基，氧代或氟基团，且任选被氧，氮，硫或磷原子间隔; R 2表示氢原子或基团R > 1 ，并且两个R 2个基团可以相同或不同），以及它们在诊断和光化学治疗身体的外部或内部表面的障碍或异常中的用途，以及产品和用于执行本发明的试剂盒。

3. 发明授权

US07563819B1 Esters of 5-aminolevulinic acid as photosensitizing agents in photochemotherapy 失效
标题翻译： 5-氨基乙酰丙酸的酯类作为光化学疗法中的光敏剂
公开(公告)号：US07563819B1
公开(公告)日：2009-07-21
申请号：US11786878
申请日：2007-04-13
申请人： Jo Klaveness , Nils Olav Nilsen , Jon Erik Braenden , Aslak Godal
发明人： Jo Klaveness , Nils Olav Nilsen , Jon Erik Braenden , Aslak Godal
IPC分类号： A61K31/21 , A61K31/22 , C07C229/00
CPC分类号： C07D213/30 , A61K31/195 , A61K41/0061 , A61K49/0021 , C07C229/22
摘要： The invention provides compounds for use in photochemotherapy or diagnosis, said compounds being branched alkyl esters or substituted alkyl esters of 5-aminolevulinic acid, or derivatives or pharmaceutically acceptable salts thereof. In particular, the invention provides compounds of formula (I): R22N—CH2COCH2CH2CO—OR1 (wherein R1 represents an optionally substituted branched alkyl (e.g. C5-30 alkyl) group, or a substituted alkyl group; R2, each of which may be the same or different, represents a hydrogen atom or an optionally substituted alkyl group, preferably a group R1; wherein said substituents are selected from hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, nitro, oxo, fluoro, —SR3, —NR32 and PR32 groups, and each alkyl group is optionally interrupted by one or more O—, —NR3—, —S— or —PR3— groups; and R3 represents a hydrogen atom or a C1-6 alkyl group) and salts thereof for us in diagnosis and photochemotherapy of disorders of abnormalities of external or internal surfaces of the body, and products and kits for performing the invention.
摘要翻译：本发明提供用于光化学疗法或诊断的化合物，所述化合物为支链烷基酯或5-氨基乙酰丙酸的取代烷基酯，或其衍生物或药学上可接受的盐。特别地，本发明提供式（I）的化合物：R 22 N-CH 2 COCH 2 CH 2 CO-OR 1（其中R 1表示任选取代的支链烷基（例如C 5-30烷基）或取代的烷基; R 2，其各自可以是相同或不同，表示氢原子或任选取代的烷基，优选基团R 1;其中所述取代基选自羟基，烷氧基，酰氧基，烷氧基羰基氧基，氨基，芳基，硝基，氧代，氟，-SR 3，-NR 32和 PR32基团，并且每个烷基任选地被一个或多个O-，-NR 3 - ，-S-或-PR 3 - 基团间隔;并且R 3表示氢原子或C 1-6烷基）及其盐身体外表面或内表面异常障碍的诊断和光化学治疗，以及用于实施本发明的产品和试剂盒。

4. 发明申请

US20080064752A1 Acid Addition Salts Of-5-Aminolevulinic Acid Or Its Derivatives 有权
标题翻译： 5-氨基乙酰丙酸或其衍生物的酸加成盐
公开(公告)号：US20080064752A1
公开(公告)日：2008-03-13
申请号：US10594361
申请日：2005-03-29
申请人： Jon Erik Braenden , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
发明人： Jon Erik Braenden , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
IPC分类号： A61K31/195 , A61P31/00 , C07C229/22 , G01N21/76
CPC分类号： A61K41/0061 , C07C229/22
摘要： The present invention provides an acid addition salt of 5-aminolevulinic acid (5-ALA) or of a 5-ALA derivative (e.g. a 5-ALA ester) with an acid which has a pKa of about 5 or less, preferably about 3 or less, with the proviso that the acid is other than hydrochloric acid. Particularly preferred salts are those derived from acids selected from the group comprising sulphonic acid and its derivatives, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid. The salts in accordance with the invention are particularly suitable for use as photosensitizing agents in diagnosis and photochemotherapy of disorders or abnormalities of external or internal surfaces of the body.
摘要翻译：本发明提供5-氨基乙酰丙酸（5-ALA）或5-ALA衍生物（例如5-ALA酯）与酸的加成盐，所述酸的pKa为约5或更小，优选约3或较少，条件是酸不是盐酸。特别优选的盐是衍生自选自磺酸及其衍生物，氢溴酸，硫酸，硝酸和磷酸的酸的酸。根据本发明的盐特别适用于诊断和光化学治疗身体的外表面或内表面的病症或异常的光敏剂。

5. 发明授权

US07217736B2 Esters of 5-aminolevulinic acid as photosensitizing agents in photochemotherapy 失效
标题翻译： 5-氨基乙酰丙酸的酯类作为光化学疗法中的光敏剂
公开(公告)号：US07217736B2
公开(公告)日：2007-05-15
申请号：US10343209
申请日：2001-07-25
申请人： Jo Klaveness , Nils Olav Nilsen , Jon Erik Braenden , Aslak Godal
发明人： Jo Klaveness , Nils Olav Nilsen , Jon Erik Braenden , Aslak Godal
IPC分类号： A61K31/21 , A61K31/195 , C07D221/00 , C07C229/00
CPC分类号： C07D213/30 , A61K31/195 , A61K41/0061 , A61K49/0021 , C07C229/22
摘要： The invention provides compounds for use in photochemotherapy or diagnosis, said compounds being branched alkyl esters or substituted alkyl esters of 5-aminolevulinic acid, or derivatives or pharmaceutically acceptable salts thereof. In particular, the invention provides compounds of formula (I): R22N—CH2COCH2CH2CO—OR1 (wherein R1 represents an optionally substituted branched alkyl (e.g. C5-30 alkyl) group, or a substituted alkyl group; R2, each of which may be the same or different, represents a hydrogen atom or an optionally substituted alkyl group, preferably a group R1; wherein said substituents are selected from hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, nitro, oxo, fluoro, —SR3, —NR32 and PR32 groups, and each alkyl group is optionally interrupted by one or more O—, —NR3—, —S— or —PR3— groups; and R3 represents a hydrogen atom or a C1-6 alkyl group) and salts thereof for use in diagnosis and photochemotherapy of disorders of abnormalities of external or internal surfaces of the body, and products and kits for performing the invention.
摘要翻译：本发明提供用于光化学疗法或诊断的化合物，所述化合物为支链烷基酯或5-氨基乙酰丙酸的取代烷基酯，或其衍生物或药学上可接受的盐。特别地，本发明提供式（I）的化合物：R 2 2 N-CH 2 COCH 2 其中R 1表示任选取代的支链烷基（例如C 5-30），其中R 1，R 2，烷基）基团或取代的烷基; R 2各自可以相同或不同，表示氢原子或任选取代的烷基，优选基团R 1，其中所述取代基选自羟基，烷氧基，酰氧基，烷氧基羰氧基，氨基，芳基，硝基，氧代，氟，-SR 3，-NR 3， 2个和3个以上的2个基团，并且每个烷基任选地被一个或多个O - ，-NR 3 - ，-S-或-PR 3+基; R 3表示氢原子或C 1-6烷基）和其盐，用于诊断和光化学治疗身体外表面或内表面异常障碍，以及p 用于实施本发明的产品和试剂盒。

6. 发明授权

US07888526B2 Acid addition salts of 5-aminolevulinic acid or its derivatives 有权
标题翻译： 5-氨基乙酰丙酸或其衍生物的酸加成盐
公开(公告)号：US07888526B2
公开(公告)日：2011-02-15
申请号：US10594361
申请日：2005-03-29
申请人： Jon Erik Braenden , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
发明人： Jon Erik Braenden , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
IPC分类号： C07C229/22 , A61K31/195
CPC分类号： A61K41/0061 , C07C229/22
摘要： The present invention provides an acid addition salt of 5-aminolevulinic acid (5-ALA) or of a 5-ALA derivative (e.g. a 5-ALA ester) with an acid which has a pKa of about 5 or less, preferably about 3 or less, with the proviso that the acid is other than hydrochloric acid. Particularly preferred salts are those derived from acids selected from the group comprising sulphonic acid and its derivatives, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid. The salts in accordance with the invention are particularly suitable for use as photosensitizing agents in diagnosis and photochemotherapy of disorders or abnormalities of external or internal surfaces of the body.
摘要翻译：本发明提供5-氨基乙酰丙酸（5-ALA）或5-ALA衍生物（例如5-ALA酯）与酸的加成盐，所述酸的pKa为约5或更小，优选约3或较少，条件是酸不是盐酸。特别优选的盐是衍生自选自磺酸及其衍生物，氢溴酸，硫酸，硝酸和磷酸的酸的酸。根据本发明的盐特别适用于诊断和光化学治疗身体的外表面或内表面的病症或异常的光敏剂。

7. 发明授权

US08692014B2 Acid addition salts of 5-aminolevulinic acid or its derivatives 有权
标题翻译： 5-氨基乙酰丙酸或其衍生物的酸加成盐
公开(公告)号：US08692014B2
公开(公告)日：2014-04-08
申请号：US12916326
申请日：2010-10-29
申请人： Jon Erik Braenden , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
发明人： Jon Erik Braenden , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
IPC分类号： C07C229/00 , A61K31/195
CPC分类号： A61K41/0061 , C07C229/22
摘要： The present invention provides an acid addition salt of 5-aminolevulinic acid (5-ALA) or of a 5-ALA derivative (e.g. a 5-ALA ester) with an acid which has a pKa of about 5 or less, preferably about 3 or less, with the proviso that the acid is other than hydrochloric acid. Particularly preferred salts are those derived from acids selected from the group comprising sulphonic acid and its derivatives, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid. The salts in accordance with the invention are particularly suitable for use as photosensitizing agents in diagnosis and photochemotherapy of disorders or abnormalities of external or internal surfaces of the body.
摘要翻译：本发明提供5-氨基乙酰丙酸（5-ALA）或5-ALA衍生物（例如5-ALA酯）与酸的加成盐，所述酸的pKa为约5或更小，优选约3或较少，条件是酸不是盐酸。特别优选的盐是衍生自选自磺酸及其衍生物，氢溴酸，硫酸，硝酸和磷酸的酸的酸。根据本发明的盐特别适用于诊断和光化学治疗身体的外表面或内表面的病症或异常的光敏剂。

8. 发明申请

US20110125012A1 ACID ADDITION SALTS OF 5-AMINOLEVULINIC ACID OR ITS DERIVATIVES 有权
标题翻译： 5-氨基酸或其衍生物的酸添加量
公开(公告)号：US20110125012A1
公开(公告)日：2011-05-26
申请号：US12916326
申请日：2010-10-29
申请人： Jon Erik BRAENDEN , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
发明人： Jon Erik BRAENDEN , Aslak Godal , Nils Olav Nilsen , Jo Klaveness
IPC分类号： A61B6/00 , C12Q1/02 , G01N21/64 , A61M37/00
CPC分类号： A61K41/0061 , C07C229/22
摘要： The present invention provides an acid addition salt of 5-aminolevulinic acid (5-ALA) or of a 5-ALA derivative (e.g. a 5-ALA ester) with an acid which has a pKa of about 5 or less, preferably about 3 or less, with the proviso that the acid is other than hydrochloric acid. Particularly preferred salts are those derived from acids selected from the group comprising sulphonic acid and its derivatives, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid. The salts in accordance with the invention are particularly suitable for use as photosensitizing agents in diagnosis and photochemotherapy of disorders or abnormalities of external or internal surfaces of the body.
摘要翻译：本发明提供5-氨基乙酰丙酸（5-ALA）或5-ALA衍生物（例如5-ALA酯）与酸的加成盐，所述酸的pKa为约5或更小，优选约3或较少，条件是酸不是盐酸。特别优选的盐是衍生自选自磺酸及其衍生物，氢溴酸，硫酸，硝酸和磷酸的酸的酸。根据本发明的盐特别适用于诊断和光化学治疗身体的外表面或内表面的病症或异常的光敏剂。

9. 发明申请

US20110020441A1 USE OF 5-AMINOLEVULINIC ACID AND DERIVATIVES IN A SOLID FORM FOR PHOTODYNAMIC TREATMENT AND DIAGNOSIS 审中-公开
标题翻译：用于光化学治疗和诊断的固体形式中的5-氨基酸和衍生物的使用
公开(公告)号：US20110020441A1
公开(公告)日：2011-01-27
申请号：US12808177
申请日：2008-12-12
申请人： Jo Klaveness , Gry Stensrud , Aslak Godal , Jon Erik Braenden , Bjorn Klem
发明人： Jo Klaveness , Gry Stensrud , Aslak Godal , Jon Erik Braenden , Bjorn Klem
IPC分类号： A61K9/48 , A61K31/197 , A61K31/221 , A61K31/24 , A61K31/44 , A61P35/00
CPC分类号： A61K9/02 , A61K9/0031 , A61K9/0034 , A61K9/0075 , A61K9/14 , A61K9/1635 , A61K9/1652 , A61K9/20 , A61K9/2013 , A61K9/205 , A61K9/2054 , A61K9/2077 , A61K9/28 , A61K9/284 , A61K9/2846 , A61K9/2866 , A61K9/2886 , A61K9/48 , A61K9/4858 , A61K9/4891 , A61K9/5042 , A61K9/5073 , A61K31/197 , A61K31/221 , A61K41/0057 , A61K41/0061 , A61K49/00 , A61K49/0021
摘要： The present invention relates to the use of a photosensitiser which is 5-ALA or a precursor or derivative thereof (e.g. an ALA ester), in the manufacture of a pharmaceutical product for use in the photodynamic treatment or diagnosis of cancer, an infection associated with cancer, or in the treatment or diagnosis of a non-cancerous condition, wherein said pharmaceutical product is in the form of a solid. The invention also relates to solid pharmaceutical products for use in such methods, e.g. suppositories, pessaries, tablets, pellets and capsules which comprise 5-ALA or a precursor or derivative thereof (e.g. an ALA ester) and at least one pharmaceutically acceptable carrier or excipient. Such products are particularly suitable for use in the photodynamic treatment or diagnosis of cancerous or non-cancerous conditions in the lower part of the gastrointestinal system or in the female reproductive system, e.g. in the treatment or diagnosis of colorectal cancer or cervical cancer.
摘要翻译：本发明涉及使用5-ALA或其前体或衍生物（例如ALA酯）的光敏剂在制造用于癌症的光动力学治疗或诊断的药物产品中，与癌症或治疗或诊断非癌症状况，其中所述药物产品为固体形式。本发明还涉及用于这些方法的固体药物产品，例如。栓剂，阴道栓剂，片剂，丸剂和胶囊，其包含5-ALA或其前体或衍生物（例如ALA酯）和至少一种药学上可接受的载体或赋形剂。这些产品特别适用于光动力学治疗或诊断胃肠系统下部或女性生殖系统中的癌性或非癌性病症。在结直肠癌或宫颈癌的治疗或诊断中。

10. 发明授权

US08759396B2 Use of aminolevulinic acid and derivatives thereof 有权
标题翻译：氨基乙酰丙酸及其衍生物的应用
公开(公告)号：US08759396B2
公开(公告)日：2014-06-24
申请号：US12523048
申请日：2008-01-11
申请人： Hans Christian Wulf , Aslak Godal , Jo Klaveness
发明人： Hans Christian Wulf , Aslak Godal , Jo Klaveness
IPC分类号： A01N37/12 , A61N1/30
CPC分类号： A61K41/0061 , A61K31/221 , A61N5/062
摘要： The invention provides the use of a photosensitizer which is 5-aminolevulinic acid (5-ALA) or a derivative (e.g. an ester) of 5-ALA, or a pharmaceutically acceptable salt thereof, in the manufacture of a composition for use in methods of photodynamic therapy (PDT) on an animal, wherein said PDT comprises: (a) administering to said animal a composition comprising said photosensitizer; and (b) photoactivating said photosensitizer, and wherein side-effects (e.g. pain and/or erythema) of said PDT are prevented or reduced by use of one or more of (i)-(iv): (i) said composition comprises said photosensitizer in a concentration of less than 10% wt (e.g. 0.5 to 8% wt), (ii) said composition is administered for less than 2 hours (e.g. 30 minutes to 90 minutes) prior to said photoactivation, (iii) said photoactivation is carried out with a light source having a fluence rate of less than 50 mW/cm2 (e.g. 5 to 40 mW/cm2), (iv) said photoactivation is carried out with sunlight. Preferably, side-effects of PDT are prevented or reduced by using (iii) or (iv) in combination with (i) and/or (ii).
摘要翻译：本发明提供了5-氨基乙酰丙酸（5-ALA）或5-ALA衍生物（例如酯）或其药学上可接受的盐的光敏剂在制备用于光动力疗法（PDT），其中所述PDT包括：（a）向所述动物施用包含所述光敏剂的组合物; 和（b）光活化所述光敏剂，并且其中通过使用（i） - （iv）中的一种或多种来防止或减少所述PDT的副作用（例如疼痛和/或红斑）：（i）所述组合物包含浓度小于10％wt（例如0.5至8％wt）的光敏剂，（ii）所述组合物在所述光活化之前施用少于2小时（例如30分钟至90分钟），（iii）所述光活化是用光通量小于50mW / cm2（例如5〜40mW / cm2）的光源进行，（iv）所述的光活化是在太阳光下进行的。优选地，通过使用（iii）或（iv）与（i）和/或（ii）组合来防止或减少PDT的副作用。

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