Isolation of clavulanic acid from fermentation broth by ultrafiltration
    3.
    发明授权
    Isolation of clavulanic acid from fermentation broth by ultrafiltration 失效
    通过超滤从发酵液中分离克拉维酸

    公开(公告)号:US6127358A

    公开(公告)日:2000-10-03

    申请号:US375

    申请日:1998-06-01

    Applicant: Egidij Capuder

    Inventor: Egidij Capuder

    CPC classification number: C12P17/188

    Abstract: Provided is a process for preparation and/or purification of clavulanic acid or a pharmaceutically acceptable salt or ester thereof including removing solids from a clavulanic acid containing fermentation broth by microfiltration to form a first filtrate, further removing solids from the first filtrate by ultrafiltration to form a second filtrate, concentrating the second filtrate by removal of water, and treating the concentrated second filtrate to isolate clavulanic acid or a pharmaceutically acceptable salt or ester thereof, characterized in that the first filtrate is filtered using an ultrafiltration membrane having a molecular weight cut-off of 10 to 30 kD and a permeate flow rate of 10 to 30 lm.sup.-2 h.sup.-1.

    Abstract translation: PCT No.PCT / GB96 / 02083 Sec。 371日期1998年6月1日 102(e)1998年6月1日PCT PCT 1996年8月27日PCT公布。 公开号WO97 / 08175 日期1997年3月6日提供了制备和/或纯化克拉维酸或其药学上可接受的盐或酯的方法,包括通过微量过滤从含有克拉维酸的发酵液中除去固体以形成第一滤液,从第一 滤液通过超滤以形成第二滤液,通过除去水浓缩第二滤液,并处理浓缩的第二滤液以分离克拉维酸或其药学上可接受的盐或酯,其特征在于使用超滤膜过滤第一滤液,所述超滤膜具有 分子量截留值为10〜30kD,渗透流量为10〜30lm-2h-1。

    Process for the isolation of clavulanic acid and of pharmaceutically
acceptable salts thereof from the fermentation broth of streptomyces
sp. P 6621 FERM P 2804
    4.
    发明授权
    Process for the isolation of clavulanic acid and of pharmaceutically acceptable salts thereof from the fermentation broth of streptomyces sp. P 6621 FERM P 2804 失效
    从链霉菌发酵液中分离克拉维酸及其药学上可接受的盐的方法 P 6621 FERM P 2804

    公开(公告)号:US5780274A

    公开(公告)日:1998-07-14

    申请号:US632402

    申请日:1996-04-10

    Applicant: Egidij Capuder

    Inventor: Egidij Capuder

    CPC classification number: C12P17/188 C07D503/00 C12N1/02 Y10S435/886

    Abstract: A process for the isolation of clavulanic acid and pharmaceutically acceptable salts thereof, such as potassium clavulanate, from the aqueous fermentation broth of a clavulanic acid-producing microorganism comprises the microfiltration of the broth without prior treatment. Additional steps may include an optional ultrafiltration of the microfiltration filtrate, concentration of the filtrate, direct extraction of the concentrated filtrate with a water-immiscible organic solvent, washing, drying, and concentration of the organic solvent, and isolation of the clavulanic acid or a pharmaceutically acceptable salt from the organic solvent.

    Abstract translation: PCT No.PCT / SI95 / 00002 Sec。 371日期:1996年4月10日 102(e)日期1996年4月10日PCT提交1995年2月23日PCT公布。 公开号WO95 / 23870 日期1995年9月8日从产生克拉维酸的微生物的水性发酵液中分离克拉维酸及其药学上可接受的盐如克拉维酸钾的方法包括没有预处理的肉汤的微量过滤。 附加步骤可以包括微滤滤液的任选的超滤,滤液的浓度,用水不混溶的有机溶剂直接萃取浓缩的滤液,洗涤,干燥和浓缩有机溶剂,以及分离克拉维酸或 来自有机溶剂的药学上可接受的盐。

    Production of a salt of clavulanic acid
    6.
    发明授权
    Production of a salt of clavulanic acid 失效
    生产克拉维酸盐

    公开(公告)号:US6133441A

    公开(公告)日:2000-10-17

    申请号:US68241

    申请日:1998-05-11

    Applicant: Helmut Wagner

    Inventor: Helmut Wagner

    CPC classification number: C07D503/00 A61K31/431

    Abstract: Process for the production of alkali salts of clavulanic acid of formula ##STR1## by conversion of clavulanic acid into a pharmaceutically acceptable salt of clavulanic acid which is characterised in that the conversion is carried out in n-butanol or iso-butanol (2-methyl-1-propanol) as a solvent; and a potassium salt of clavulanic acid containing n-butanol or iso-butanol.

    Abstract translation: PCT No.PCT / EP96 / 05015 Sec。 371日期:1998年5月11日 102(e)日期1998年5月11日PCT 1996年11月14日PCT PCT。 公开号WO97 / 18216 日期1997年5月22日通过将克拉维酸转化成药学上可接受的克拉维酸的盐的克拉维酸碱盐的制备方法,其特征在于转化在正丁醇或异丁醇(2- 甲基-1-丙醇)作为溶剂; 和含有正丁醇或异丁醇的克拉维酸钾盐。

    Process for the preparation of a salt clavulanic acid
    7.
    发明授权
    Process for the preparation of a salt clavulanic acid 失效
    制备盐酸克拉维酸的方法

    公开(公告)号:US5965728A

    公开(公告)日:1999-10-12

    申请号:US663158

    申请日:1996-08-21

    CPC classification number: C07D503/00

    Abstract: A process for the preparation of a salt of clavulanic acid, wherein clavulanic acid in solution in a wholly or partly water-imiscible organic solvent is contacted in a region of high turbulence and/or shear stress, with a salt precursor compound to form a solution of the salt of clavulanic acid in an aqueous phase, then the organic solvent and aqueous phases are physically separated during a separation step, followed by a further processing step in which the said salt of clavulanic acid is isolated from solution as a solid.

    Abstract translation: PCT No.PCT / GB95 / 00191 Sec。 371日期:1996年8月21日 102(e)日期1996年8月21日PCT提交1995年1月31日PCT公布。 WO95 / 21173 PCT出版物 日期1995年8月10日一种制备克拉维酸盐的方法,其中在全部或部分水不可混溶的有机溶剂中的溶液中的克拉维酸在高湍流和/或剪切应力的区域与盐前体接触 化合物形成克拉维酸盐在水相中的溶液,然后有机溶剂和水相在分离步骤期间物理分离,随后是进一步的加工步骤,其中所述的克拉维酸盐从溶液中分离为 一个坚实

    Diamine salts of clavulanic acid
    8.
    发明授权
    Diamine salts of clavulanic acid 失效
    二酸盐的克拉维酸

    公开(公告)号:US5821364A

    公开(公告)日:1998-10-13

    申请号:US338585

    申请日:1994-11-14

    CPC classification number: C07D503/00

    Abstract: New diamine salts of clavulanic acid, pharmaceutical compositions comprising the same, and a new process using these diamine salts in the preparation of clavulanic acid and salts and esters thereof have been provided.

    Abstract translation: PCT No.PCT / EP94 / 00919 Sec。 371日期:1994年11月14日 102(e)日期1994年11月14日PCT 1994年3月22日PCT公布。 WO94 / 22873 PCT出版物 日期:1994年10月13日提供了克拉维酸的两种二胺盐,包含它们的药物组合物,以及使用这些二胺盐制备克拉维酸及其盐和酯的新方法。

    Inclusion complexes of clavulanic acid and of alkali salts thereof with
hydrophilic and hydrophobic .beta.-cyclodextrin derivatives, a process
for the preparation thereof and the use thereof
    9.
    发明授权
    Inclusion complexes of clavulanic acid and of alkali salts thereof with hydrophilic and hydrophobic .beta.-cyclodextrin derivatives, a process for the preparation thereof and the use thereof 失效
    克拉维酸及其碱金属盐与亲水和疏水性β-环糊精衍生物的包合物,其制备方法及其用途

    公开(公告)号:US5614199A

    公开(公告)日:1997-03-25

    申请号:US470267

    申请日:1995-06-06

    CPC classification number: B82Y5/00 A61K31/42 A61K31/424 A61K47/48969

    Abstract: Described is a new process for the preparation of alkali clavulanate from an aqueous solution of crude clavulanic acid, which is obtained in a conventional manner after the fermentation with a clavulanic-acid-producing microorganism, extracted with an ethyl acetate solution of a hydrophobic .beta.-CD derivative such as heptakis-(2,3,6-tri-O-acetyl)-.beta.-CD in at least equimolar ratio with regard to clavulanic acid. The resulting novel inclusion complexes of clavulanic acid and hydrophobic .beta.-CD derivative in a molar ratio about 1:1 are isolated, purified and then converted with an alkali base or alkali alkanoate to the desired alkali clavulanate, which is isolated. Furthermore, there are described new inclusion complexes of clavulanic acid and of its pharmaceutically acceptable alkali salts both with hydrophilic .beta.-CD derivatives and with hydrophobic .beta.-CD derivatives, processes for the preparation thereof and the use thereof for the preparation of galenic forms with immediate as well as with sustained action, in combination with amoxicillin trihydrate, which are valuable medicaments in the therapy of infectious diseases.

    Abstract translation: 描述了一种从粗制棒酸的水溶液制备克拉维酸碱的新方法,该方法是在用产生克拉维酸的微生物发酵之后以常规方式获得的,用疏水性β-葡聚糖的乙酸乙酯溶液萃取, CD衍生物,如克拉维酸至少等摩尔比例的七( - ) - (2,3,6-三-O-乙酰基)-β-CD。 所得到的克拉维酸和疏水性β-CD衍生物的摩尔比约为1:1的新型包合物被分离,纯化,然后用碱金属碱或碱金属酸碱转化成所需的克拉维酸碱盐,将其分离。 此外,还描述了克拉维酸及其药学上可接受的碱金属盐与亲水性β-CD衍生物和疏水性β-CD衍生物的新型包合配合物,其制备方法及其用于立即制备盖仑制剂的用途 以及持续的作用,与阿莫西林三水合物组合,这是治疗传染病的有价值的药物。

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