发明公开
EP2781505A1 Positively charged water-soluble prodrugs of prostaglandins and related compounds with very high skin penetration rates
审中-公开
带正电的前列腺素和相关化合物的水溶性前药具有非常高的Hautpenetrierungswerten
- 专利标题: Positively charged water-soluble prodrugs of prostaglandins and related compounds with very high skin penetration rates
- 专利标题(中): 带正电的前列腺素和相关化合物的水溶性前药具有非常高的Hautpenetrierungswerten
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申请号: EP14156640.6申请日: 2006-10-02
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公开(公告)号: EP2781505A1公开(公告)日: 2014-09-24
- 发明人: Yu, Chongxi , Xu, Lina
- 申请人: Techfields Biochem Co. Ltd , Yu, Chongxi
- 申请人地址: Techfields Biochem 2399 Jinqiu Road 129 Shanghai N/A 200444 CN
- 专利权人: Techfields Biochem Co. Ltd,Yu, Chongxi
- 当前专利权人: Techfields Biochem Co. Ltd,Yu, Chongxi
- 当前专利权人地址: Techfields Biochem 2399 Jinqiu Road 129 Shanghai N/A 200444 CN
- 代理机构: Viering, Jentschura & Partner Patent- und Rechtsanwälte
- 主分类号: C07C215/40
- IPC分类号: C07C215/40 ; C07C215/42 ; C07C405/00 ; A61K31/5575 ; A61P9/12 ; A61P15/00
摘要:
The novel positively charged pro-drugs of prostaglandins, prostacyclins and related compounds in the general formula (2) 'Structure 2' were designed and synthesized. The compounds of the general formula (2) 'Structure 2' indicated above can be prepared from protected prostaglandins, prostacyclins, and related compounds, by reaction with suitable alcohols, thiols, or amines and coupling reagents, such as N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, Benzotriazol-1-yl-oxy-tris (dimethylamino)phosphonium hexafluorophosphate, et al. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drugs diffuse through human skin ∼1000 times faster than do prostaglandins, prostacyclins, and related compounds. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any prostaglandins, prostacyclins, and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of prostaglandins, prostacyclins, and related compounds. Controlled transdermal administration systems of the prodrug enable prostaglandins, prostacyclins, and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of prostaglandins, prostacyclins, and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.
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