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1. 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。

2. 发明申请

US20120134921A1 SOLID COMPOSITIONS COMPRISING 5-AMINOLEVULINIC ACID 审中-公开
标题翻译：包含5-氨基酸的固体组合物
公开(公告)号：US20120134921A1
公开(公告)日：2012-05-31
申请号：US13377692
申请日：2010-06-11
申请人： Oddveig Sellaeg Helland , Gry Stensrud , Bjorn Klem , Jon Erik Braenden , Aslak Godal , Jo Klavenes
发明人： Oddveig Sellaeg Helland , Gry Stensrud , Bjorn Klem , Jon Erik Braenden , Aslak Godal , Jo Klavenes
IPC分类号： A61K51/04 , A61K49/00
CPC分类号： A61K31/197 , A61K9/0009 , A61K9/4858 , A61K41/0061 , A61K49/0036
摘要： This invention relates to solid compositions and solid pharmaceutical products for use in methods of photodynamic diagnosis of cancer, pre-cancerous and non-cancerous conditions in the lower part of the gastrointestinal system. The solid pharmaceutical compositions and pharmaceutical products comprise an active ingredient which is 5-aminolevulinic acid (5-ALA) or a precursor or derivative of 5-ALA or pharmaceutically acceptable salts thereof. The invention relates further to methods of photodynamic diagnosis of cancer, pre-cancerous and non-cancerous conditions of the lower gastrointestinal tract, wherein the solid pharmaceutical compositions and pharmaceutical products are used.
摘要翻译：本发明涉及用于癌症的光动力学诊断方法，胃肠系统下部癌前和非癌症病症的固体组合物和固体药物产品。固体药物组合物和药物产品包含5-氨基乙酰丙酸（5-ALA）或5-ALA的前体或衍生物的活性成分或其药学上可接受的盐。本发明还涉及癌症的光动力学诊断方法，下胃肠道的癌前和非癌症状况，其中使用固体药物组合物和药物产品。

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

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。

6. 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。

7. 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。

8. 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。

9. 发明申请

US20140010761A1 FORM OF HEXYL-5-AMINOLEVULINATE HYDROCHLORIDE AND METHODS OF USING THE SAME 有权
标题翻译：甲基五氨基丙烯酸氢氯化物的形式及其使用方法
公开(公告)号：US20140010761A1
公开(公告)日：2014-01-09
申请号：US13930497
申请日：2013-06-28
申请人： Stephan D. Parent , Jon Erik Braenden
发明人： Stephan D. Parent , Jon Erik Braenden
IPC分类号： C07C229/22 , A61K49/00
CPC分类号： C07C229/22 , A61K41/0061 , A61K49/0052 , C07B2200/13
摘要： This invention relates to a novel crystalline polymorph of hexyl-5-aminolevulinate hydrochloride, referred to hereinafter as Form C, which is useful as precursor of a photo sensitizer in the photodynamic diagnosis and treatment of metabolically active cells related to diseases such as cancer of the uterus, cervix, vagina, rectum, colon, lower gastrointestinal tract; infection associated with cancer caused by human papilloma virus; non-cancerous lower gastrointestinal tract a human; inflammatory bowel disease; ulcerative colitis; Crohn's disease; inflammatory bowel syndrome; dysplasia of the female reproductive system; anus; penis; rosacea; and acne and which is suitable for use as the active ingredient of a commercial pharmaceutical product. The invention relates further to methods of preparing Form C and using it in the described pharmaceutical compositions.
摘要翻译：本发明涉及一种新型的5-己基-5-氨基乙酰丙酸盐酸盐的结晶多晶型物，以下称为C型，其可用作光致敏剂的前体，用于光动力学诊断和治疗与诸如癌症的疾病相关的代谢活性细胞子宫，子宫颈，阴道，直肠，结肠，下胃肠道; 与人乳头状瘤病毒引起的癌症相关的感染; 非癌性下胃肠道一人; 炎症性肠病; 溃疡性结肠炎克罗恩病; 炎性肠综合征; 女性生殖系统发育异常; 肛门; 阴茎红斑痤疮和粉刺，并且其适合用作商业药物产品的活性成分。本发明进一步涉及制备形式C并将其用于所述药物组合物中的方法。

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