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    • 2. 发明授权
    • Crystal suspensions of insulin derivatives, processes for their
preparation and their use
    • 胰岛素衍生物的晶体悬浮液,其制备方法及其用途
    • US4959351A
    • 1990-09-25
    • US635257
    • 1984-07-27
    • Ulrich Grau
    • Ulrich Grau
    • A61K38/28A61K38/00C07K14/575C07K14/62
    • C07K14/622C07K14/62C30B7/00A61K38/00
    • The invention relates to a process for the preparation of crystal suspensions of one or more insulin derivatives of the formula I ##STR1## R.sup.1 denotes H or H-Phe, R.sup.30 represents the radical of a neutral L-aminoacid which can be genetically coded andR.sup.31 represents a physiologically acceptable organic group of basic character with up to 50 carbon atoms, in the build-up of which 0 to 3 .alpha.-aminoacids participate and in which any terminal carboxyl function present can be free, as the ester function, as the amide function, as the lactone or reduced to CH.sub.2 OH, with an isoelectric point between 5.8 and 8.5,which comprises carrying out the crystallization in an aqueous medium close to the isoelectric point of the derivative or derivatives in the presence of an aromatic hydroxy compound, to crystals and crystal suspensions obtained by the process and to the use thereof.
    • 本发明涉及一种制备一种或多种式I的胰岛素衍生物的晶体悬浮液的方法,其中R 1表示H或H-Phe,R 30表示可以在遗传上的中性L-氨基酸的基团 编码,R31代表具有多达50个碳原子的基本特征的生理上可接受的有机基团,其中0至3个α-氨基酸参与并且其中存在的任何末端羧基官能团可以作为酯官能团, 作为酰胺官能团,作为内酯或还原成CH2OH,等电点为5.8〜8.5,其包括在芳族羟基化合物存在下在接近衍生物或衍生物的等电点的水性介质中进行结晶 ,通过该方法获得的晶体和晶体悬浮液及其用途。
    • 4. 发明授权
    • Electrically rotatable shaft
    • 电动轴
    • US06684831B2
    • 2004-02-03
    • US10128900
    • 2002-04-24
    • Ulrich Grau
    • Ulrich Grau
    • F01L134
    • F01L13/0015F01L13/0026F01L2013/0073F01L2103/01F01L2201/00F01L2800/13
    • The invention concerns an electrically rotatable shaft, and more particularly, an adjusting shaft (1) of a fully variable mechanical valve train of an internal combustion engine, said shaft comprising an adjusting cam (2). The low-friction and lash-free configuration of a drive required for a rapid and exact functioning of the fully variable mechanical valve train is achieved by the fact that the adjusting shaft (1) is rotated by an actuator (3) that comprises an adjusting lever (4) connected rotationally fast to the adjusting shaft (1), while the free end of the adjusting lever is articulated preferably on the screw nut (10) of a screw-and-nut drive (5) that is driven by an electromotor (6).
    • 本发明涉及一种电动旋转的轴,更具体地说,涉及一种内燃机的全可变的机械气门机构的调节轴(1),所述轴包括调节凸轮(2)。 完全可变的机械气门机构的快速和精确地运行所需的驱动器的低摩擦和无间隙构造通过以下事实实现:调节轴(1)由包括调节器(3)的致动器(3)旋转, 杠杆(4)旋转地快速地连接到调节轴(1),而调节杆的自由端优选地铰接在由电动机驱动的螺母和螺母驱动器(5)的螺母(10)上 (6)。
    • 5. 发明授权
    • Process for the preparation of insulin derivatives, the B chain of which
is lengthened c-terminally
    • 胰岛素衍生物的制备方法,其B链延长c末端
    • US5015728A
    • 1991-05-14
    • US172236
    • 1988-03-23
    • Rainer ObermeierRolf GeigerUlrich Grau
    • Rainer ObermeierRolf GeigerUlrich Grau
    • C07K14/575A61K38/00A61K38/28A61P5/00C07K14/62C12P21/02
    • C07K14/62A61K38/00Y02P20/55
    • The invention relates to a process for the preparation of an insulin derivative of the formula I ##STR1## in which R.sup.1 denotes H or H-Phe, R.sup.30 represents the radical of a naturally occurring L-aminoacid and R.sup.31 represents a physiologically acceptable organic group of neutral or basic character consisting of 1 to 3 .alpha.-aminoacids in which the terminal carboxyl function is present in the free form and which insulin derivative has an isoelectric point above 5.8, which comprises reacting an insulin of the formula I in which R.sup.30 denotes the radical of a genetically codable L-aminoacid and R.sup.31 represents OH or a protective group of the carboxyl function, with a peptide or aminoacid derivatives of the formula R-R.sup.30 -R.sup.31 consisting of 2 to 4 .alpha.-aminocacids, in which the terminal carboxyl function is in free form, in the presence of a trypsin-like endopeptidase at a pH value below the isoelectric point of the starting insulin.
    • 本发明涉及一种制备式I(I)的胰岛素衍生物的方法,其中R1表示H或H-Phe,R30表示天然存在的L-氨基酸的基团,R31表示生理上可接受的 由1〜3个α-氨基酸组成的中性或碱性有机基团,其中末端羧基官能团以游离形式存在,哪种胰岛素衍生物具有高于5.8的等电点,其包括使式I的胰岛素与R30 表示可遗传编码的L-氨基酸的基团,R31表示OH或羧基官能团的保护基团,具有由2至4个α-氨基酸组成的式R-R30-R31的肽或氨基酸衍生物,其中末端 在胰蛋白酶样内肽酶的存在下,羧基功能是游离形式,其pH值低于起始胰岛素的等电点。
    • 8. 发明授权
    • Process for obtaining insulin precursors from reaction mixtures
resulting from the folding of insulin precursors from the corresponding
S-sulfonates
    • 从由相应的S-磺酸盐折叠胰岛素前体产生的反应混合物获得胰岛素前体的方法
    • US4801684A
    • 1989-01-31
    • US924850
    • 1986-09-02
    • Ulrich Grau
    • Ulrich Grau
    • C07K1/30C07K1/107C07K1/113C07K14/575C07K14/62C07K14/625C07K7/40
    • C07K14/625Y10S930/26
    • A process for the preparation of insulin precursors of the formula (I) ##STR1## in which R is hydrogen or the presequence P.sub.m --Q.sub.n --, in which P is a sequence of naturally occurring amino acids with m being from 0 to 50, Q are basic natural amino acids, and n is an integer from 1 to 4, Y represents --Lys.sup.B29 --Z.sup.B30 --, in which Z denotes Ala, Thr or Ser, and the bridge extending from A-1 to A-21 is an insulin A-chain, the bridge extending from B-1 to B-30 represents an insulin B-chain, and X is a bridge which is bonded to the insulin A-chain at the amino group of A-1 and is bonded to the insulin B-chain at the .epsilon.-amino group of B-29-- in which case it is bonded to the free bond of Z.sup.B30 OH-- or at the carboxyl group of B-30, from reaction mixtures which result from folding of insulin precursors from S-sulfonates of the formula (II) ##STR2## in which R, X and Y have the abovementioned meanings, which comprises the false recombinants contained in the reaction mixture being precipitated by adjustment of the reaction mixture to pH 4 to 6, the precipitate being removed in customary manner and converted by sulfitolysis into the S-sulfonate of the formula (II), and the latter then being subjected to renewed folding.
    • PCT No.PCT / EP86 / 00008 Sec。 371日期1986年9月2日第 102(e)1986年9月2日PCT PCT 1月11日,PCT PCT。 出版物WO86 / 04335 日期:1986年7月31日。一种制备式(I)的胰岛素前体的方法,其中R是氢或前序Pm-Qn-,其中P是天然存在的氨基 具有0至50的m,Q是碱性天然氨基酸,n是1至4的整数,Y表示-LysB29-ZB30-,其中Z表示Ala,Thr或Ser,并且从A延伸的桥 -1至A-21是胰岛素A链,从B-1延伸到B-30的桥表示胰岛素B链,X是与氨基的氨基上的胰岛素A链结合的桥 A-1,并且在B-29-的ε-氨基处与胰岛素B链结合,在这种情况下,它与ZB30OH的游离键或B-30的羧基结合,由反应混合物 其中R,X和Y具有上述含义的式(II)的S-磺酸盐的胰岛素前体的折叠,其包含反应混合物中包含的假重组体 通过将反应混合物调节至pH4至6沉淀,以常规方式除去沉淀物并通过亚硫酸解转化成式(II)的S-磺酸盐,然后将其再进行折叠。
    • 10. 发明授权
    • Arrangement with a helical spring and a support bearing for spring struts
    • 具有螺旋弹簧和弹簧支柱的支撑轴承的布置
    • US06550755B2
    • 2003-04-22
    • US09937958
    • 2002-03-15
    • Herbert EhrhardtUlrich GrauGerhard MeyerAlexander ZernickelVladimir KobelevMarkus Röhling
    • Herbert EhrhardtUlrich GrauGerhard MeyerAlexander ZernickelVladimir KobelevMarkus Röhling
    • F16F106
    • B60G15/068B60G15/063B60G15/07B60G2200/142B60G2200/44B60G2202/312B60G2204/1242B60G2204/418B60G2206/426
    • A coil spring (1) and support bearing (2) arrangement for suspension struts (3) with a shock absorber, supporting a steering knuckle of an automobile has a rolling-contact bearing (7), with an axis (x); a receiving body (6), arranged below the rolling-contact bearing (7) in which the rolling-contact bearing is inserted; and a coil spring (1). The coil spring (1) has a force application line (f), which is offset relative to the axis (x) of the rolling-contact bearing (7) at an angle (a). The coil spring (1) has a first portion (8), which, starting from the winding end (17), winds around the receiving body (6). The first portion (8) abuts the receiving body (6). The winding end (17) of the coil spring (1) is arranged in the area of the plane E1 formed by the force application line (f) and the axis (x). Thus, the axial forces acting from the coil spring (1) onto the rolling-contact bearing (7) have a maximum in the area of the force application line (f) of the transversal forces acting on the rolling-contact bearing (7).
    • 具有支撑汽车转向节的减振器的悬挂支杆(3)的螺旋弹簧(1)和支撑轴承(2)布置具有轴线(x)的滚动接触轴承(7)。 接收体(6),布置在滚动接触轴承(7)的下方,滚动接触轴承插入其中; 和螺旋弹簧(1)。 螺旋弹簧(1)具有力作用线(f),其相对于滚动接触轴承(7)的轴线(x)以角度(a)偏移。 螺旋弹簧(1)具有从卷绕端(17)开始的第一部分(8)绕着接收体(6)缠绕。 第一部分(8)邻接接收体(6)。 螺旋弹簧(1)的卷绕端(17)布置在由施力线(f)和轴线(x)形成的平面E1的区域中。 因此,从螺旋弹簧(1)作用到滚动接触轴承(7)上的轴向力在作用在滚动接触轴承(7)上的横向力的施力线(f)的面积上具有最大值, 。