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1. 发明授权

US4647552A Process for obtaining ready for fertilization sexual products from sexually mature fish 失效
标题翻译：从性成熟鱼获得受精性产品的准备过程
公开(公告)号：US4647552A
公开(公告)日：1987-03-03
申请号：US684066
申请日：1984-12-20
申请人： Tamas Gulyas , Aniko Horvath , Gyorgy Keri , Karoly Nikolics , Balazs Szoke , Istvan Teplan
发明人： Tamas Gulyas , Aniko Horvath , Gyorgy Keri , Karoly Nikolics , Balazs Szoke , Istvan Teplan
IPC分类号： A01K61/00 , A61K38/00 , C07K7/06 , C07K7/23 , C07K14/575 , A61K37/24
CPC分类号： C07K7/23 , A61K38/00 , Y10S514/80 , Y10S930/13
摘要： The invention relates to a process for obtaining ready-for-fertilization sexual products from sexually mature fish in a period independent of their natural spawning season, in which actual stage of ripening is determined by probing of sexual products [sperm or eggs], fish not yet ripe for ovulation are separated from ripe fish, compounds of hormonal effect are administered to fish, and after the ovulation sexual products are obtained from the fish or from their environment.In the process according to the invention a nonapeptide-C.sub.1-4 -alkyl-amide or a decapeptide amide of the general formula (I),Glp-His-Trp-Ser-Tyr-X.sub.1 -X.sub.2 -X.sub.3 -Pro-X.sub.4 (I)whereinX.sub.1 is a glycyl group or a D-isomer of any natural or synthetic amino acid group,X.sub.2 represents an L-amino acid group having 1 to 4 carbon atoms in the side chain, L-phenyl-alanyl or L-tryptophyl group,X.sub.3 represents an L-amino acid group having a C.sub.1-4 alkyl or C.sub.2-4 alkyl-amide side chain,X.sub.4 is a glycine-amide or a C.sub.1-4 alkyl-amide group,as well as salts or metal-complexes of these compounds are administered to fish in a dose of 0.1 .mu.g to 5 mg, and to fish not yet ripe for ovulation the above quantities are administered in at least 2 but at most 12 portions, wherein the last dose used is at least the same or advantageously at least 1.5 times higher than the previous one.The process according to the invention makes possible the obtaining of ripe sexual products ready for natural or artificial fertilization from any fish species in any period, independently of the natural spawning season of fish.
摘要翻译：本发明涉及一种独立于自然产卵季节从性成熟鱼获得即食受精性产品的方法，其中成熟的实际阶段是通过探查性产品[精子或卵]，鱼类成熟的排卵与成熟的鱼分离，激素作用的化合物被施用于鱼，并且在排卵之后，从鱼或其环境获得性产物。在根据本发明的方法中，通式（I）的Glc-His-Trp-Ser-Tyr-X1-X2-X3-Pro-X4（I）的非肽-C1-4-烷基酰胺或十肽酰胺）其中X1是任何天然或合成氨基酸基团的甘氨酰基或D-异构体，X2表示侧链中具有1至4个碳原子的L-氨基酸基团，L-苯丙氨酰基或L-色氨酸基团，X3表示具有C1-4烷基或C2-4烷基 - 酰胺侧链的L-氨基酸基，X4是甘氨酸 - 酰胺或C1-4烷基 - 酰胺基，以及盐或金属络合物这些化合物以0.1μg至5mg的剂量施用于鱼，并且为了排卵尚未成熟，上述量以至少2但最多12份施用，其中使用的最后剂量至少相同或有利地比前一个高至少1.5倍。根据本发明的方法使得可以在任何时间段内获得准备好从任何鱼类进行天然或人造受精的成熟性产品，而与鱼的天然产卵季节无关。

2. 发明授权

US4758552A Gonadoliberin derivatives containing an aromatic aminocarboxylic acid in the 6-position, pharmaceutical and veterinary compositions containing them and process for preparing same 失效
标题翻译：在6-位含有芳香族氨基羧酸的甘那球蛋白衍生物，含有它们的药物和兽医组合物及其制备方法
公开(公告)号：US4758552A
公开(公告)日：1988-07-19
申请号：US177
申请日：1987-01-02
申请人： Tamas Gulyas , Istvan Teplan , Aniko Horvath , Gyorgy Keri , Bokonyi Istvane , Sandor Vigh
发明人： Tamas Gulyas , Istvan Teplan , Aniko Horvath , Gyorgy Keri , Bokonyi Istvane , Sandor Vigh
IPC分类号： A61K38/04 , A61K38/00 , A61P15/00 , C07K1/02 , C07K1/04 , C07K7/06 , C07K7/23 , C07K14/575 , A61K37/43 , C07K7/20
CPC分类号： C07K7/23 , A61K38/00 , Y10S514/80 , Y10S930/11 , Y10S930/13
摘要： The invention relates to novel gonadoliberin nonapeptide ethylamide or decapeptide amide derivatives of the general formula (I),Glp-His-Trp-Ser-Tyr-X.sub.1 -X.sub.2 -X.sub.3 -Pro-X.sub.4 (I)whereinX.sub.1 stands for a 2-aminobenzoic or 3-aminobenzoic acid group;X.sub.2 stands for a leucyl, tryptophyl or phenylalanyl group;X.sub.3 means an arginyl, leucyl or glutaminyl group; andX.sub.4 represents a glycylamide or ethylamide group, as well as their acid addition salts and pharmaceutical presparations containing these compounds. Further on, the invention relates to a process for preparing these compounds and preparations.The gonadoliberin derivatives of the invention can more effectively be used for reproduction biological purposes as compared to the derivatives known so far.
摘要翻译：本发明涉及通式（I），Glp-His-Trp-Ser-Tyr-X1-X2-X3-Pro-X4（Ⅰ）的新颖性促性白列素壬肽乙酰胺或十肽酰胺衍生物，其中X1代表2-氨基苯甲酸或3-氨基苯甲酸基团; X2代表亮氨酰，色氨酸或苯丙氨酰基; X3表示精氨酰，亮氨酰或谷氨酰胺基; 并且X 4代表甘氨酰酰胺或乙酰胺基团，以及它们的酸加成盐和含有这些化合物的药物预制剂。此外，本发明涉及一种制备这些化合物和制剂的方法。与迄今已知的衍生物相比，本发明的性腺激肽衍生物可更有效地用于生殖生物学目的。

3. 发明授权

US4647553A Gonadoliberin derivatives and process for the preparation thereof 失效
标题翻译： Gonadoliberin衍生物及其制备方法
公开(公告)号：US4647553A
公开(公告)日：1987-03-03
申请号：US684065
申请日：1984-12-20
申请人： Tamas Gulyas , Aniko Horvath , Gyorgy Keri , Karoly Nikolics , Balazs Szoke , Istvan Teplan
发明人： Tamas Gulyas , Aniko Horvath , Gyorgy Keri , Karoly Nikolics , Balazs Szoke , Istvan Teplan
IPC分类号： C07K14/575 , A61K38/00 , A61K38/08 , A61K38/24 , A61P5/00 , C07K7/06 , C07K7/23 , A61K37/43 , C07K7/20
CPC分类号： C07K7/23 , A61K38/00 , Y10S514/80 , Y10S930/13
摘要： The invention relates to gonadoliberin derivatives of the general formula (I)Glp--His--Trp--Ser--Tyr--X.sub.1 --X.sub.2 --X.sub.3 --Pro--X.sub.4whereinX.sub.1 is a glycyl group or a D-isomer of any natural or synthetic amino acid group,X.sub.2 represents an L-amino acid group having 1 to 4 carbon atoms in the side chain, L-phenyl-alanyl or L-tryptophyl group,X.sub.3 represents an L-amino acid group having a C.sub.1-4 alkyl or C.sub.2-4 alkanoyl-amide side chain, andX.sub.4 is a glycine amide or a C.sub.1-4 alkyl amide group,with the proviso that if X.sub.1 stands for a group other than glycyl and X.sub.2 is a tryptophyl group then X.sub.3 may not be leucyl, and the addition salts formed with therapeutically useable acids and complexes thereof. Furthermore the invention relates to a process for preparing these compounds.The new gonadoliberin derivatives can be effectively used for the reproduction process of fish, birds and mammals.
摘要翻译：本发明涉及通式（I）Glp-His-Trp-Ser-Tyr-X1-X2-X3-Pro-X4的性腺蛋白衍生物，其中X1是任何天然或合成氨基酸的甘氨酰基或D-异构体基团，X2表示侧链具有1〜4个碳原子的L-氨基酸基，L-苯丙氨酰或L-色氨酰基，X3表示具有C1-4烷基或C2-4的L-氨基酸烷酰基酰胺侧链，X4为甘氨酸酰胺或C1-4烷基酰胺基，条件是如果X1表示除甘氨酰以外的基团，X2表示色氨酸基，则X3不可以是亮氨酰基，加成与治疗上可用的酸及其复合物形成的盐。此外，本发明涉及一种制备这些化合物的方法。新的促性腺激肽衍生物可以有效地用于鱼，鸟和哺乳动物的繁殖过程。

4. 发明授权

US4753928A Process for obtaining sexual products from mammals suitable for natural or artificial fertilization 失效
标题翻译：从适合天然或人工受精的哺乳动物获得性产品的过程
公开(公告)号：US4753928A
公开(公告)日：1988-06-28
申请号：US886618
申请日：1986-07-18
申请人： Tamas Gulyas , Csaba Banhazi , Zoltan Graf , Aniko Horvath , Gyorgy Keri , Eszter Kovats , Istvan Teplan
发明人： Tamas Gulyas , Csaba Banhazi , Zoltan Graf , Aniko Horvath , Gyorgy Keri , Eszter Kovats , Istvan Teplan
IPC分类号： A61K35/12 , A61K38/00 , A61K38/04 , A61K38/08 , A61K38/09 , A61K38/22 , A61P5/00 , A61P13/02 , A61P15/00 , C07K7/23 , C07K14/575 , A61K37/43
CPC分类号： A61K38/09 , Y10S514/80 , Y10S930/13
摘要： The invention relates to a process for producing sexual products suitable for natural or artificial fertilization from mammalia through controlling the activity of their sexual organs in their pre- and post-natal lives, during their infancy, puberty and mature state and, in a given case, to produce offsprings from them as well as to increase several times the production of sexual products to a level far above that typical of the life's performance of the species. According to the invention the mammalia are treated at least once and at most 60 times with a compound of general formula (I),Glp-His-Trp-Ser-Tyr-X.sub.1 -X.sub.2 -X.sub.3 -Pro-X.sub.4, (I)whereinX.sub.1 means a glycil-group or any other natural or synthetic D-aminoacid group,X.sub.2 means an L-aminoacid-group with a side chain of an alkyl-, phenyl, or triptophyl group containing 1-4 carbon atoms,X.sub.3 means an L-aminoacid group having a side chain of an alkyl group with 1-4 carbon atoms or an alkanoyl-amide group of 2-4 carbon atoms andX.sub.4 means a glycil-amide or an alkylamide group of 1-4 carbon atoms,or a salt or metal complex thereof in a dose of 0.01 to 500 .mu.g/body weight kg (bwkg), preferably 1 to 100 .mu.g/bwkg, wherein intervals of at least two hours and at most 7 days, preferably 2 to 8 hours, are kept between the individual treatments.
摘要翻译：本发明涉及通过在其婴儿期，青春期和成熟状态下控制其性器官在其生前和产后生活中的活性来产生适合于哺乳动物自然或人造受精的性产品的方法，并且在给定的情况下，以产生他们的后代，并将性产品的数量增加到远远高于该物种的生命表现的典型水平。根据本发明，用通式（I）的化合物，Glp-His-Trp-Ser-Tyr-X1-X2-X3-Pro-X4，（I）至少治疗一次至多60次， X1表示甘氨酰基或任何其他天然或合成的D-氨基酸基团，X2表示具有1-4个碳原子的烷基 - ，苯基或triptophyl基团侧链的L-氨基酸，X3表示L 具有1-4个碳原子的烷基或2-4个碳原子的烷酰基 - 酰胺基的侧链的氨基酸组，X 4表示1个碳原子的甘氨酰胺或烷酰胺基，或盐或其金属络合物，其剂量为0.01〜500μg/体重kg（bwkg），优选为1〜100μg/ bwkg，其中间隔至少2小时，最多7天，优选2〜8小时为保持个人治疗之间。

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