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91. 发明公开

EP0432479A1 Anhydrous pharmaceutical formulations and dosage forms for the rectal administration of calcitonin 失效
标题翻译： Wasserfreie Arzneizubereitungen und Dosierformen zur rektalen Verabreichung von calcitonin。
公开(公告)号：EP0432479A1
公开(公告)日：1991-06-19
申请号：EP90121670.5
申请日：1990-11-13
申请人： SCLAVO S.p.A.
发明人： Lattanzi, Filippo , Vanni, Riccardo
IPC分类号： A61K9/48 , A61K9/66 , A61K47/10 , A61K37/30
CPC分类号： A61K9/4858 , A61K9/4866 , A61K38/23 , A61K47/42
摘要： New formulations are described containing a calcitonin as active principle and suitable for rectal administration in the form of soft gelatin capsules, in which the active principle, possibly mixed with a stabilizer, is dispersed in a liquid vehicle consisting of a polyethyleneglycol or a mixture of polyethyleneglycols of different molecular weight which has the consistency of a homogeneous fluid at ambient temperature, and possibly a C₂-C₆ alcohol with at least 2 hydroxyl groups, and present in a weight quantity of less than 15%. Said formulations, which contain no absorption adjuvant, enable the same pattern of hematic levels to be obtained as obtainable by conventional intramuscular administration, for equal unit dosages. Moreover, the absence of water makes said formulations highly stable.
摘要翻译：描述了含有降钙素作为活性成分并适用于软明胶胶囊形式的直肠给药的新制剂，其中可能与稳定剂混合的活性成分分散在由聚乙二醇或聚乙二醇混合物组成的液体载剂中不同的分子量，其在环境温度下具有均匀流体的稠度，以及可能具有至少2个羟基的C2-C6醇，并且重量小于15％。不含吸收助剂的所述制剂能够通过常规的肌内给药获得相同的单位剂量模式的血浆水平。而且，没有水使得制剂高度稳定。

92. 发明公开

EP0375047A3 New process for the synthesis of N alpha-fluorenylmethoxycarbonyl-Ng-trityl-arginine 失效
标题翻译：合成N-阿尔法 - 氟代甲氧基羰基亚氨基 - 三羟甲基纤维素的新工艺
公开(公告)号：EP0375047A3
公开(公告)日：1991-03-06
申请号：EP89203211.1
申请日：1989-12-18
申请人： SCLAVO S.p.A.
发明人： Caciagli, Valerio , Verdini, Antonio Silvio
IPC分类号： C07C279/14
CPC分类号： C07K1/064 , C07C279/14 , C07C2603/18
摘要： An improvement is described in the synthesis method for N α -trityl-N G -trityl-arginine within a process for preparing N α -fluorenylmethoxycarbonyl-N G -trityl-arginine from arginine, comprising:
a) forming N α -trityl-N G -trityl-arginine b) selectively detaching the trityl group from the α-NH₂ and c) introducing the fluorenylmethoxycarbonyl group in its place. The improvement consists of preparing the N α -trityl-N G -trityl-arginine by solubilizing the arginine in an aprotic organic solvent by tri-alkylsilylation both of the amino nitrogen and of the carboxyl group, followed by tritylation, with trityl chloride, of the α-amino nitrogen, and of the guanidino group after deprotonating this latter with a bicyclic guanidine. The new improved process can also lead to variable quantities of the arginine analogue di-tritylated at the guanidino group, namely N α -fluorenylmethoxycarbonyl-N G -di-trityl-arginine. This new compound, to which the present invention also relates, can also be used as such in peptide synthesis.
摘要翻译：在从精氨酸制备N - 芴基甲氧基羰基-N' - 三苯甲基 - 精氨酸的方法中，在N，N-三苯甲基-N 3 - 三苯甲基 - 精氨酸的合成方法中描述了一种改进，其包括：）形成N， - 三苯甲基-N 3 - 三苯甲基 - 精氨酸b）选择性地从α-NH 2中分离三苯甲基，和c）将芴基甲氧基羰基引入其位置。该改进包括通过将氨基氮和羧基三烷基硅烷化，然后进行三苯甲基化，通过将精氨酸溶解在非质子有机溶剂中，然后进行三苯甲基三缩三乙胺，制备N - 三苯甲基-N' - 三苯甲基 - 精氨酸，氯化三苯甲酰，α-氨基氮和胍基的胍基，后者用双环胍去质子化。新的改进方法也可导致胍基上二精氨酸类似物的可变量，即N-芴基甲氧基羰基-N， - 三 - 三苯甲基 - 精氨酸。本发明也涉及的这种新化合物也可以原样用于肽合成中。

93. 发明公开

EP0392095A3 Tuftsin analogues and vaccines containing these as adjuvants 失效
标题翻译： TUFTSIN类似物和包含这些作为ADJUVANTS的疫苗
公开(公告)号：EP0392095A3
公开(公告)日：1991-01-30
申请号：EP89201371.5
申请日：1989-05-30
申请人： SCLAVO S.p.A.
发明人： Nencioni, Luciano , Pileri, Piero , Peppoloni, Samuele , Silvestri, Sergio
IPC分类号： C07K5/02 , A61K39/39
CPC分类号： C07K5/0212 , A61K39/00
摘要： The invention is concerned with compounds analogous to tuftsin, having the formula (I)
or of a pharmaceutically acceptable base-addition or acid-addition salt thereof, and the use of them in vaccines as an adjuvant in order to potentiate, in a living organism, the antibody response against either natural or synthetic antigens, as well as with the novel compositions for vaccines which comprise one or more of said antigens together with an adjuvating amount of the compound of formula (I) or of one of its addition salts.

94. 发明公开

EP0396964A1 Pertussis toxin mutants, bordetella strains capable of producing such mutants and their use in the development of antipertussis vaccines 有权转让
标题翻译：百日咳毒素突变体，同样的生产百日咳博德特氏菌及其作为抗百日咳疫苗的使用。
公开(公告)号：EP0396964A1
公开(公告)日：1990-11-14
申请号：EP90107892.3
申请日：1990-04-25
申请人： SCLAVO S.p.A.
发明人： Pizza, Mariagrazia , Covacci, Antonello , Rappuoli, Rino , Nencioni, Luciano
IPC分类号： A61K39/10 , C12N15/31
CPC分类号： C07K14/235 , A61K39/00 , A61K39/099
摘要： New pertussis toxin (PT) mutants are described being immunologically active and having reduced or no toxicity, characterized in that at least one of the aminoacid residues Glu129, Asp11, Trp26, Arg9, Phe50, Asp1, Arg13, Tyr130, Gly86, Ile88, Tyr89, Tyr8, Gly 44, Thr53 and Gly80 of subunit's 1 aminoacid sequence is deleted and substituted by a different aminoacid residue selected in the group of natural aminoacids; Bordetella strains capable of providing and secreting said PT mutants and means and methods for obtaining them are also described.
The Bordetella strains and the PT mutants produced by them are particularly suitable for the preparation of effective cellular and acellular antipertussis vaccines.
摘要翻译：新百日咳毒素（PT）的突变体被描述为免疫活性和具有降低的或没有毒性，在其特点做的氨基酸残基Glu129，Asp11，Trp26，Arg9，Phe50，ASP1，Arg13，Tyr130，Gly86，Ile88，Tyr89的至少一个，酪氨酸8，甘氨酸44，Thr53和亚单位的1个氨基酸序列的Gly80被删除，并且由组天然氨基酸中选择的不同氨基酸残基substituiertem; 博代氏杆菌菌株能够提供和分泌。所述PT突变体和手段和方法用于获得它们被这样描述的。博德特氏菌菌株和由它们产生的PT突变体特别适合于有效的细胞和非细胞疫苗antipertussis的制备。

95. 发明公开

EP0384523A2 New gem-diamino derivatives and their use in the synthesis of retro-inverso peptides 失效
标题翻译： Gem-diamino-Derivate und ihre Verwendung bei der Herstellung von Retro-Inverso-Peptiden。
公开(公告)号：EP0384523A2
公开(公告)日：1990-08-29
申请号：EP90200352.4
申请日：1990-02-16
申请人： ENIRICERCHE S.p.A. , SCLAVO S.p.A.
发明人： Gazerro, Laura , Pinori, Massimo , Verdini, Antonio Silvio
IPC分类号： C07C235/10 , C07C235/78 , C07K1/06 , C07K5/02
CPC分类号： C07K1/063 , C07C235/20 , C07C235/34 , C07C237/20 , C07C237/22 , C07C271/22 , C07K5/0212
摘要： This invention relates to new gem-diamino derivatives of general formula (I)
where

R is the side chain of an amino acid, of which any functional groups are suitably protected, and
X is an acyl group chosen from the group consisting of 2-nitro-benzoyl, 4-chloro-butyryl, acetoacetyl, 4-bromo-butyryl, (2-nitro-phenoxy)-acetyl and 2-methyl-2-(2'-nitro-phenoxy)propionyl, of use in introducing gem-diamino residues into retro-inverso peptides. The invention further relates to a method for the synthesis of retro-inverso peptides in which the gem-diamino residue or residues are introduced using the new compound (I).
摘要翻译：本发明涉及通式（I）X-NH-H-NH 2（I）的新的偕二氨基衍生物，其中R是氨基酸的侧链，其中任何官能团都被适当地保护，X是选自2-硝基 - 苯甲酰基，4-氯 - 丁酰基，乙酰乙酰基，4-溴 - 丁酰基，（2-硝基 - 苯氧基） - 乙酰基和2-甲基-2-（2min - 苯氧基）丙酰基，用于将偕二氨基残基引入逆转肽。本发明还涉及一种用于合成其中使用新化合物（I）引入偕二氨基残基或残基的逆转肽的方法。

96. 发明公开

EP0375047A2 New process for the synthesis of N alpha-fluorenylmethoxycarbonyl-Ng-trityl-arginine 失效
标题翻译： Verfahren zur Herstellung von N-α-芴基甲氧基 - 羰基-Gn-三苯甲基 - 精氨酸。
公开(公告)号：EP0375047A2
公开(公告)日：1990-06-27
申请号：EP89203211.1
申请日：1989-12-18
申请人： SCLAVO S.p.A.
发明人： Caciagli, Valerio , Verdini, Antonio Silvio
IPC分类号： C07C279/14
CPC分类号： C07K1/064 , C07C279/14 , C07C2603/18
摘要： An improvement is described in the synthesis method for N α -trityl-N G -trityl-arginine within a process for preparing N α -fluorenylmethoxycarbonyl-N G -trityl-arginine from arginine, comprising:

a) forming N α -trityl-N G -trityl-arginine
b) selectively detaching the trityl group from the α-NH₂ and
c) introducing the fluorenylmethoxycarbonyl group in its place.

The improvement consists of preparing the N α -trityl-N G -trityl-arginine by solubilizing the arginine in an aprotic organic solvent by tri-alkylsilylation both of the amino nitrogen and of the carboxyl group, followed by tritylation, with trityl chloride, of the α-amino nitrogen, and of the guanidino group after deprotonating this latter with a bicyclic guanidine.
The new improved process can also lead to variable quantities of the arginine analogue di-tritylated at the guanidino group, namely N α -fluorenylmethoxycarbonyl-N G -di-trityl-arginine. This new compound, to which the present invention also relates, can also be used as such in peptide synthesis.
摘要翻译：在从精氨酸制备N - 芴基甲氧基羰基-N' - 三苯甲基 - 精氨酸的方法中，在N，N-三苯甲基-N 3 - 三苯甲基 - 精氨酸的合成方法中描述了一种改进，其包括：）形成N， - 三苯甲基-N 3 - 三苯甲基 - 精氨酸b）选择性地从α-NH 2中分离三苯甲基，和c）将芴基甲氧基羰基引入其位置。该改进包括通过将氨基氮和羧基三烷基硅烷化，然后进行三苯甲基化，通过将精氨酸溶解在非质子有机溶剂中，然后进行三苯甲基三缩三乙胺，制备N - 三苯甲基-N' - 三苯甲基 - 精氨酸，氯化三苯甲酰，α-氨基氮和胍基的胍基，后者用双环胍去质子化。新的改进方法也可导致胍基上二精氨酸类似物的可变量，即N-芴基甲氧基羰基-N， - 三 - 三苯甲基 - 精氨酸。本发明也涉及的这种新化合物也可以原样用于肽合成中。

97. 发明公开

EP0320866A3 A protective immunodominant epitope included in the S1 subunit of pertussis toxin 失效
标题翻译：包含在PERTUSSIS毒素S1亚型中的保护性免疫调节蛋白
公开(公告)号：EP0320866A3
公开(公告)日：1990-06-20
申请号：EP88120779.9
申请日：1988-12-13
申请人： SCLAVO S.p.A.
发明人： Bartoloni, Antonella , Pizza, Mariagrazia , Rappuoli, Rino
IPC分类号： C07K13/00 , C12N15/00 , A61K39/10
CPC分类号： C07K14/235 , A61K39/00
摘要： There are described a protective immunodominant epitope of pertussis toxin which is included in the S1 subunit, and synthetic peptides with an aminoacid sequence similar to that of the epitope or to regions thereof which show an immunochemical reactivity with anti-PT protective monoclonal antibodies equivalent to that of the protein itself. Ihe peptides are particularly useful for the preparation of an antipertussis vaccine.

98. 发明公开

EP0357137A2 New silylating agent for the preparation of chromatographic supports 失效
标题翻译： Silylierungsmittel zur Herstellung von色谱仪Trägern。
公开(公告)号：EP0357137A2
公开(公告)日：1990-03-07
申请号：EP89202171.8
申请日：1989-08-28
申请人： ENIRICERCHE S.p.A. , SCLAVO S.p.A.
发明人： Cardinali, Franco , Longobardi, Maria Grazia , Viscomi, Giuseppe Claudio , Ziggiotti, Alessandra
IPC分类号： C07F7/18 , B01J20/32
CPC分类号： C07F7/1896 , B01J20/103 , B01J20/28004 , B01J20/286 , B01J20/3071 , B01J20/3078 , B01J20/3085 , B01J20/3092 , B01J20/3204 , B01J20/3246 , B01J2220/54 , B01J2220/58
摘要： A new mono-silylating agent of general formula (I)
(R₁,R₂,R₃)Si-NH-CO-O-Si(R₁,R₂,R₃) (I)
is described as well as its use in the preparation of chromatographic supports based on silica with functional groups covalently bonded thereto, the so-called "bonded stationary phases".
The new compounds are easy and safe to prepare from the corresponding mono-halosilanes with ammonium carbamate, and their use as silylating agents leads to stationary phases with a higher degree of surface coating than that attainable with the corresponding chlorosilanes.
摘要翻译：描述了通式（I）（R1，R2，R3）Si-NH-CO-O-Si（R1，R2，R3）（Ⅰ）的新单甲硅烷基化剂及其在色谱法制备中的应用基于与其共价键合的官能团的二氧化硅的载体，即所谓的“键合固定相”。新化合物由相应的单卤硅烷与氨基甲酸铵制备容易和安全，并且它们作为甲硅烷基化剂的用途导致具有比相应的氯硅烷可获得的更高程度的表面涂层的固定相。

99. 发明公开

EP0353814A2 Synthetic peptide endowed with immunological activity, capable of inducing the production of antibodies with a high specificity towards alpha-fetoprotein, and their use in the diagnostic field 失效
标题翻译：合成肽具有免疫活性，从而促进了生产与抗甲胎蛋白高特异性，以及它们在诊断领域使用抗体。
公开(公告)号：EP0353814A2
公开(公告)日：1990-02-07
申请号：EP89201926.6
申请日：1989-07-21
申请人： SCLAVO S.p.A.
发明人： Tecce, Mario Felice , Giuliani, Marzia Monica , Ricci, Stefano , Ratti, Giulio , Terrana, Benedetto
IPC分类号： C07K7/10 , C12N15/00 , G01N33/53
CPC分类号： C12N9/1252 , C07K14/4715 , C07K16/30 , C07K16/303 , C07K2319/00 , C07K2319/30
摘要： A synthetic peptide endowed with immunological activity is disclosed, which is capable of inducing in mammals the formation of anti-peptide antibodies capable of recognizing human alpha-fetoprotein and of reacting with it, and incapable of recognizing albumin or its degradation products, with said peptide being essentially constituted by the aminoacidic sequence of formula (I), corresponding to 38- 119 region of human alpha-fetoprotein.
Furthermore, the methods and means for preparing said peptide by means of the recombinant DNA techniques are reported.
The synthetic peptide (I), like the polyclonal and monoclonal antipeptide antibodies are particularly suitable for the early diagnosis of hepatocellular carcinoma and of teratocarcinoma.
摘要翻译：赋有免疫学活性的合成肽是圆盘游离缺失，所有其能够在哺乳动物中诱导能够识别人甲胎蛋白和与之发生反应的抗肽抗体的形成，并且不能识别白蛋白或其降解产物的，与所述肽基本上由式（I）的aminoacidic序列构成的，对应于38-人甲胎蛋白的119区域。进一步，用于制备和手段的方法的由所述的重组DNA技术的肽的报道。合成肽（I），如多克隆抗体和单克隆抗肽抗体特别适合用于畸胎癌的肝细胞癌和早期诊断。

100. 发明公开

EP0336412A2 Synthetic oligonucleotides useful for the determination of Chlamydia trachomatis in a biological sample 失效
标题翻译： Synthetische寡核苷酸zum Nachweis von沙眼衣原体在einer生物制品中探针。
公开(公告)号：EP0336412A2
公开(公告)日：1989-10-11
申请号：EP89106059.2
申请日：1989-04-06
申请人： SCLAVO S.p.A.
发明人： Ratti,Giulio , Comanducci,Maurizio , Ricci,Stefano , Garuti,Giancarlo , Cosco,Egidio
IPC分类号： C12Q1/68
CPC分类号： C07K14/295 , C12Q1/6841 , C12Q1/689
摘要： The nucleotide sequence of the PCHL1 plasmid which is specific to Chlamydia trachomatis (CT) is reported. Synthetic oligonucleotides with sequences homologous or corresponding to a region of at least 10 consecutive nucleotide bases selected from the sequence of the plasmid are particularly useful for the determination of CT in a biological sample.
摘要翻译：报道了对沙眼衣原体（CT）特异性的PCHL1质粒的核苷酸序列。具有同源或对应于选自质粒序列的至少10个连续核苷酸碱基的区域的序列的合成寡核苷酸特别可用于测定生物样品中的CT。

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